CN109996583A - Methods and devices for stimulating blood vessels to control, treat and/or prevent bleeding - Google Patents

Abstract

A method of preventing, treating and/or controlling bleeding in an organ of a patient comprises providing electrical stimulation to an artery, a vein, a nerve innervating an artery or a vein, or a wall of an organ. The device has at least one electrode operably connected to a stimulation generator and placed in electrical communication with the artery, vein, nerve or wall of the organ. The electrical stimulation generator causes electrical stimulation to be applied to the artery, vein, nerve or wall through the at least one electrode, wherein the electrical stimulation is effective for preventing, treating and/or controlling bleeding.

Description

Methods and devices for stimulating blood vessels to control, treat and/or prevent bleeding

cross reference

This application relies in priority on U.S. Provisional Patent Application No. 62/328,303, filed April 27, 2016, and entitled "Method and Apparatus for Stimulating Blood Vessels for Modulating Blood Flow" and filed March 7, 2016 of the same title of US Provisional Patent Application No. 62/304,841.

This application is also a continuation-in-part of US Patent Application No. 14/728,630, filed June 2, 2015, entitled "Method and Apparatus for Stimulating the Vascular System," which was filed October 2009 US Patent Application No. 12/575,713 filed on July 14, 2015 as a continuation of the same title as US Patent Application No. 9,079,028, which is relied on in priority on October 2008 U.S. Provisional Patent Application No. 61/104,054 of the same title, filed on the 9th.

All of the above applications are incorporated herein by reference in their entirety.

Field of Invention

The present specification relates to the use of electrical stimulation to regulate blood flow and, more particularly, to prevent, control and/or treat bleeding by stimulating arteries, veins, or nerves supplying the arteries and veins of a patient.

Background of the Invention

Trauma is the leading cause of death in Americans under the age of 44. Hemorrhagic shock accounts for 30-40% of traumatic mortality. Bleeding is also the most common preventable cause of death on the battlefield. The use of tourniquets in compressible bleeding resulted in a significant reduction in limb exsanguination. Bleeding that does not fit a truncal tourniquet (also known as non-compressible hemorrhage) is now the leading cause of preventable death, according to the U.S. Army. Some non-compressible hemorrhages occur as a result of bleeding into a body cavity such as the abdomen or chest, while others result from trauma at the junction between the trunk and the extremities or neck.

Effective blood loss prevention in the prehospital setting offers the best chance of saving soldiers with non-compressible lesions, and therefore, significant efforts have been made to develop technologies that address this unmet need. It has been demonstrated that thrombus formation can be induced in clamped vessels by the application of direct current for up to several minutes. However, the associated thermal injury precludes the use of this technique in clinical practice.

Furthermore, bleeding is the leading cause of death in the operating room worldwide. About 4 out of every 10,000 surgical patients and 6 out of every 10,000 patients who receive anesthesia suffer fatal cardiac arrest within 30 days of surgery. Bleeding accounted for 33% of these cardiac arrests.

Therefore, there is a need for a rapid and effective method of preventing or controlling bleeding conditions in organs without causing tissue damage. This type of bleeding control applies to all bleeding situations, especially in combat and operating room scenarios.

SUMMARY OF THE INVENTION

The present specification discloses a method of preventing anticipated bleeding in an artery or vein of a patient's upper extremity using at least one electrode in electrical communication with a pulse generator, the method comprising: disposing the at least one electrode proximate the surface of the patient's artery or vein where the artery is subclavian artery, axillary artery, deep brachial artery, brachial artery, radial artery, ulnar artery, deep palmar arch, at least one of the superficial palmar arch or the vein is subclavian vein, axillary vein, at least one of the cephalic vein, brachial vein, radial vein, ulnar vein, deep palmar arch, superficial palmar arch, epicardial vein, median cubital vein, and median forearm vein, and wherein said location is at least upstream of said location of expected bleeding 1 cm; and causing the pulse generator to generate electrical stimulation applied to the artery or the vein through at least one electrode, wherein the electrical stimulation has a pulse duration, a pulse amplitude and a pulse frequency, and wherein the pulse duration is selected The time, the pulse amplitude, and the pulse frequency are such that the electrical stimulation is effective to cause vasoconstriction in the artery or vein, thereby preventing the expected bleeding.

Optionally, the pulse duration is in the range of 1 μsec to 500 msec, the pulse amplitude is in the range of 1 V to 250 V, and the pulse frequency is in the range of 1 Hz to 100 kHz.

Optionally, the at least one electrode is at least one of a cuff electrode and a clamp electrode, and disposing the at least one electrode includes placing the cuff electrode or the clamp electrode into direct physical contact with the location.

Optionally, a radio frequency (RF) receiver is coupled to the at least one electrode, and an RF transmitter is coupled to the pulse generator and in wireless communication with the RF receiver, and wherein the method further comprises The pulse generator is caused to generate electrical stimulation to be administered by the at least one electrode and wirelessly transmit the electrical stimulation from the RF transmitter to the RF receiver.

The method may also include using a microprocessor operably connected to the pulse generator to selectively set the pulse duration, the pulse amplitude, and the pulse frequency.

The present specification also discloses a method of preventing anticipated bleeding in an artery or vein of a lower extremity of a patient using at least one electrode in electrical communication with a pulse generator, the method comprising: disposing the at least one electrode in close proximity to the patient. A location on the surface of an artery or vein, wherein the artery is at least one of the femoral artery, the popliteal artery, the anterior tibial artery, the posterior tibial artery, the peroneal artery, the dorsal foot artery, and the plantar artery or the vein is the external iliac vein, the femoral artery at least one of a vein, perforating vein, great saphenous vein, lesser saphenous vein, anterior tibial vein, posterior tibial vein, and dorsal venous arch, and wherein said location is at least 1 cm upstream of said expected bleeding location; and said A pulse generator produces electrical stimulation applied to the artery or the vein through at least one electrode, wherein the electrical stimulation has a pulse duration, a pulse amplitude and a pulse frequency, and wherein the pulse duration, the pulse amplitude are selected and the pulse frequency such that the electrical stimulation is effective to cause vasoconstriction in the artery or vein, thereby preventing the expected bleeding.

Optionally, the pulse duration is in the range of 1 μsec to 500 msec, the pulse amplitude is in the range of 1 V to 250 V, and the pulse frequency is in the range of 1 Hz to 100 kHz.

Optionally, at least one electrode is a skin electrode or a clamp electrode, and disposing the at least one electrode includes placing the skin electrode or the clamp electrode in direct physical contact with the location.

Optionally, a radio frequency (RF) receiver is coupled to the at least one electrode, and an RF transmitter is coupled to the pulse generator and in wireless communication with the RF receiver, and the method further includes enabling The pulse generator generates electrical stimulation to be administered by the at least one electrode and wirelessly transmits the electrical stimulation from the RF transmitter to the RF receiver.

The method may also include using a microprocessor operably connected to the pulse generator to selectively set the pulse duration, the pulse amplitude, and the pulse frequency.

The present specification also discloses a method of controlling bleeding in a patient prior to a planned surgical procedure, the method comprising: initiating surgery in an abdominal region of the patient; placing at least one electrode of a stimulation device on the patient prior to the formation of the bleeding at a location in electrical communication with a blood vessel upstream of and supplying blood to a blood vessel in the abdominal region; connecting the at least one electrode to an electrical pulse generator; identifying bleeding during the surgical procedure; and causing the pulse to occur The device generates electrical stimulation applied to an upstream vessel, wherein the electrical stimulation has a pulse duration, a pulse amplitude, and a pulse frequency, and wherein the pulse duration, the pulse amplitude, and the pulse frequency are selected such that the electrical stimulation Effectively causes vasoconstriction of the upstream vessels and reduces blood flow to control bleeding of the vessels in the abdominal region.

Optionally, the pulse duration is in the range of 1 μsec to 500 msec, the pulse amplitude is in the range of 1 V to 250 V, and the pulse frequency is in the range of 1 Hz to 100 kHz.

Optionally, the at least one electrode is a skin electrode or a clamp electrode, and disposing the at least one electrode includes placing the skin electrode or the clamp electrode in direct physical contact with the location.

Optionally, a radio frequency (RF) receiver is coupled to the at least one electrode, and an RF transmitter is coupled to the pulse generator and in wireless communication with the RF receiver, and the method further includes enabling The pulse generator generates electrical stimulation to be administered by the at least one electrode and wirelessly transmits the electrical stimulation from the RF transmitter to the RF receiver.

The method may also include selectively setting the pulse duration, the pulse amplitude, and the pulse frequency using a microprocessor operably connected to the pulse generator.

The present specification also discloses a method of preventing bleeding in a patient prior to a planned surgical procedure, the method comprising: initiating surgery in an abdominal region of the patient, wherein initiating surgery is defined as exposing proximate to the surgery involved in the surgery an area of a blood vessel in the abdominal region; placing at least one electrode of a stimulation device at a location in electrical communication with a blood vessel upstream of and supplying blood to the blood vessel in the abdominal region prior to the formation of said hemorrhage; placing said at least one electrode electrodes connected to an electrical pulse generator; continuing the procedure; causing the pulse generator to generate electrical stimulation applied to an upstream vessel for a predetermined period of time prior to initiating a surgical technique in anticipation of an increased likelihood of bleeding, wherein the electrical The stimulation has a pulse duration, a pulse amplitude, and a pulse frequency, and wherein the pulse duration, the pulse amplitude, and the pulse frequency are selected such that the electrical stimulation is effective to cause vasoconstriction of the upstream vessel and reduce blood flow to Bleeding of blood vessels in the abdominal region is prevented; and the surgical technique is continued.

Optionally, the predetermined period of time is equal to at least 30 seconds.

Optionally, the electrical stimulation is administered for at least 10 seconds during the surgical procedure technique.

Optionally, the electrical stimulation is administered prior to beginning the surgical technique and during the remainder of the procedure.

Optionally, the at least one electrode is configured to remain in the abdominal region for a period ranging from 1 to 7 days, and wherein the electrical stimulation is administered postoperatively to treat postoperative bleeding.

The present specification discloses a method of treating bleeding in an artery or vein of a patient's upper extremity using at least one electrode in electrical communication with a pulse generator, the method comprising: disposing the at least one electrode proximate the surface of the patient's artery or vein where the artery is subclavian artery, axillary artery, deep brachial artery, brachial artery, radial artery, ulnar artery, deep palmar arch, at least one of the superficial palmar arch or the vein is subclavian vein, axillary vein, at least one of the cephalic vein, brachial vein, radial vein, ulnar vein, deep palmar arch, superficial palmar arch, epicardial vein, median cubital vein, and median forearm vein, and wherein said location is at least upstream of said location of expected bleeding 1 cm; and causing the pulse generator to generate electrical stimulation applied to the artery or the vein through at least one electrode, wherein the electrical stimulation has a pulse duration, a pulse amplitude and a pulse frequency, and wherein the pulse duration is selected The time, the pulse amplitude, and the pulse frequency are such that the electrical stimulation is effective to induce vasoconstriction in the artery or the vein.

The pulse duration can range from 1 μsec to 500 msec, the pulse amplitude can range from 1 V to 250 V, and the pulse frequency can range from 1 Hz to 100 kHz.

Optionally, at least one electrode is a skin electrode or a clamp electrode, and disposing the at least one electrode includes placing the skin electrode or the clamp electrode in direct physical contact with the location.

Optionally, a radio frequency (RF) receiver is coupled to the at least one electrode, and an RF transmitter is coupled to the pulse generator and in wireless communication with the RF receiver, and the method further includes enabling the The pulse generator generates electrical stimulation to be administered by the at least one electrode and wirelessly transmits the electrical stimulation from the RF transmitter to the RF receiver.

Optionally, the method further comprises using a microprocessor operably connected to the pulse generator to selectively set the pulse duration, the pulse amplitude and the pulse frequency.

The present specification also discloses a method of treating bleeding in an artery or vein of a patient's lower extremity using at least one electrode in electrical communication with a pulse generator, the method comprising: placing the at least one electrode proximate the patient's artery Or at the position of the surface of the vein, wherein the artery is at least one of the femoral artery, the popliteal artery, the anterior tibial artery, the posterior tibial artery, the peroneal artery, the dorsal artery and the plantar or the vein is the external iliac vein, the femoral vein , at least one of the perforating vein, the great saphenous vein, the lesser saphenous vein, the anterior tibial vein, the posterior tibial vein, and the dorsal venous arch, and wherein said location is at least 1 cm upstream of the location of said expected bleeding; and causing said pulse The generator produces electrical stimulation applied to the artery or the vein through at least one electrode, wherein the electrical stimulation has a pulse duration, a pulse amplitude and a pulse frequency, and wherein the pulse duration, the pulse amplitude and the pulse frequency are selected The pulse frequency is such that the electrical stimulation is effective to induce vasoconstriction in the artery or the vein.

The pulse duration can range from 1 μsec to 500 msec, the pulse amplitude can range from 1 V to 250 V, and the pulse frequency can range from 1 Hz to 100 kHz.

Optionally, the at least one electrode is a skin electrode or a clamp electrode, and disposing the at least one electrode includes placing the skin electrode or the clamp electrode in physical contact with the location.

Optionally, a radio frequency (RF) receiver is coupled to the at least one electrode, and an RF transmitter is coupled to the pulse generator and in wireless communication with the RF receiver, and the method further includes enabling the The pulse generator generates electrical stimulation to be administered by the at least one electrode and wirelessly transmits the electrical stimulation from the RF transmitter to the RF receiver.

Optionally, the method further comprises using a microprocessor operably connected to the pulse generator to selectively set the pulse duration, the pulse amplitude and the pulse frequency.

The present specification also discloses a method of preventing or treating bleeding in a patient prior to a planned surgical procedure, the method comprising: initiating surgery in an abdominal region of the patient; deploying at least one electrode of a stimulation device prior to the formation of the bleeding at a location in electrical communication with a blood vessel in the abdominal region upstream of and supplying blood to the blood vessel; connecting the at least one electrode to an electrical pulse generator; identifying bleeding during the surgical procedure; and causing the pulse generator to Generates electrical stimulation applied to an upstream vessel, wherein the electrical stimulation has a pulse duration, a pulse amplitude, and a pulse frequency, and wherein the pulse duration, the pulse amplitude, and the pulse frequency are selected such that the electrical stimulation is effective to elicit all vasoconstriction of the upstream vessels and reduce blood flow to prevent or control bleeding in the vessels involved in the abdominal region. The pulsed stimulation may be applied for at least 30 seconds prior to the onset of such bleeding, thereby reducing the frequency or severity of such bleeding.

The pulse duration can range from 1 μsec to 500 msec, the pulse amplitude can range from 1 V to 250 V, and the pulse frequency can range from 1 Hz to 100 kHz.

Optionally, at least one electrode is a skin electrode or a clamp electrode, and disposing the at least one electrode includes placing the skin electrode or the clamp electrode in physical contact with the location.

Optionally, a radio frequency (RF) receiver is coupled to the at least one electrode, and an RF transmitter is coupled to the pulse generator and in wireless communication with the RF receiver, and the method further includes enabling the The pulse generator generates electrical stimulation to be administered by the at least one electrode and wirelessly transmits the electrical stimulation from the RF transmitter to the RF receiver.

Optionally, the method further comprises using a microprocessor operably connected to the pulse generator to selectively set the pulse duration, the pulse amplitude and the pulse frequency.

The present specification also discloses a method of treating bleeding in a body organ of a patient, the method comprising: arranging at least one electrode of a stimulation device proximate an artery supplying blood to the body organ, a vein supplying blood from the body organ, supplying the artery or all the nerve of the vein, or the wall of the body organ; connecting the at least one electrode to an electrical pulse generator; and applying the pulse generator to an artery, vein, nerve or the body organ through the at least one electrode electrical stimulation of the walls of the body, wherein the electrical stimulation is effective to cause vasoconstriction and reduce blood flow to the body organs. Optionally, the electrodes of the stimulation device are in electrical communication with an artery supplying blood to a body organ, a vein supplying blood from a body organ, a nerve supplying said artery or said vein, or a wall of said body organ.

The electrical stimulation may have a pulse duration ranging from 1 μsec to 500 msec, a pulse amplitude ranging from 1 V to 250 V, and a pulse frequency ranging from 1 Hz to 100 kHz.

Optionally, the electrode is a clip electrode or a clamp electrode, and disposing at least one electrode near an artery, a vein, a nerve supplying the artery or the vein, or the wall of the body organ comprises attaching the clip electrode. Electrodes or the clamp electrodes are placed in physical contact with the artery, vein, nerve or wall.

Optionally, a radio frequency (RF) receiver is coupled to the at least one electrode, and an RF transmitter is coupled to the pulse generator and in wireless communication with the RF receiver, and the method further includes enabling the The pulse generator generates electrical stimulation to be administered by the at least one electrode and wirelessly transmits the electrical stimulation from the RF transmitter to the RF receiver.

Optionally, the device further comprises a microprocessor operably connected to the pulse generator, wherein at least one parameter of stimulation is controlled by the microprocessor, and wherein the method further comprises controlling the pulse generator using the microprocessor to Generate electrical stimulation.

The present specification also discloses a method of regulating blood flow to an organ of a patient, the method comprising: providing a device including at least one electrode operably connected to a pulse generator; placing the at least one electrode in contact with an artery supplying blood to the organ , a vein supplying blood from an organ or a neural electrical communication supplying said artery or said vein; and causing a pulse generator to generate electrical stimulation applied to an artery, vein or nerve through at least one electrode, wherein the electrical stimulation is effective to modulate blood flow to the organ flow.

Stimulation can be effective in constricting arteries or veins.

The electrical stimulation may have a pulse duration ranging from 1 μsec to 500 msec, a pulse amplitude ranging from 1 V to 250 V, and a pulse frequency ranging from 1 Hz to 100 kHz.

Optionally, the electrode is a clip electrode or a clamp electrode, and disposing at least one electrode near an artery, a vein, a nerve supplying the artery or the vein, or the wall of the body organ comprises attaching the clip electrode. Electrodes or the clamp electrodes are placed in physical contact with the artery, vein, nerve or wall.

Optionally, a radio frequency (RF) receiver is coupled to the at least one electrode, and an RF transmitter is coupled to the pulse generator and in wireless communication with the RF receiver, and the method further includes enabling the The pulse generator generates electrical stimulation to be administered by the at least one electrode and wirelessly transmits the electrical stimulation from the RF transmitter to the RF receiver.

Optionally, the apparatus further comprises a microprocessor operably connected to the pulse generator, wherein at least one parameter of stimulation is controlled by the microprocessor, and wherein the method further comprises using the microprocessor to control the pulse generator to generate electrical stimulation.

The present specification also discloses a method of regulating blood flow to an organ of a patient, the method comprising: providing a device including at least one electrode operably connected to a pulse generator; electrically communicating the at least one electrode with the organ wall; and causing The stimulation generator produces electrical stimulation administered near the wall through the at least one electrode, wherein the electrical stimulation is effective to modulate blood flow to the organ.

Stimulation can effectively constrict or dilate one or more blood vessels within an organ wall, thereby altering blood flow through the blood vessels.

Optionally, a radio frequency (RF) receiver is coupled to the at least one electrode, and an RF transmitter is coupled to the pulse generator and in wireless communication with the RF receiver, and the method further includes enabling The pulse generator generates electrical stimulation to be administered by the at least one electrode and wirelessly transmits the electrical stimulation from the RF transmitter to the RF receiver.

Optionally, the device further comprises a microprocessor operably connected to the pulse generator, wherein at least one parameter of stimulation is controlled by the microprocessor, and wherein the method further comprises controlling the pulse generator using the microprocessor to Generate electrical stimulation.

The present specification also discloses a method of controlling blood flow to an organ, comprising the steps of: disposing at least one electrode proximate an artery, vein, or nerve supplying the artery and vein, and activating the electrode to provide electrical stimulation thereto, wherein The electrical stimulation effectively controls blood flow to the organ.

The present specification also discloses a method of controlling blood flow to an organ, comprising the steps of disposing at least one electrode proximate an artery supplying blood to an organ, a vein supplying blood from an organ, or a nerve supplying said artery or said vein, and Activating the electrode to provide a first electrical stimulation thereto, wherein the first electrical stimulation is effective to reduce blood flow to the organ to prevent bleeding and activating the electrode to provide a second electrical stimulation thereto, wherein the second electrical stimulation Stimulation Stimulation effectively reduces blood flow to organs to treat bleeding.

The present specification also discloses a method of preventing intraoperative bleeding, comprising the steps of: placing at least one electrode near or in electrical contact with the artery, vein, or nerve supplying the artery and vein, and activating the The electrodes are used to provide electrical stimulation thereto, wherein the electrical stimulation is effective to control blood flow in an artery or vein.

The present specification also discloses a method of treating intraoperative hemorrhage, comprising the steps of: placing at least one electrode proximate an artery, vein, or nerve supplying the artery and vein, and activating the electrode to provide electrical stimulation thereto, wherein the electrical Stimulation effectively controls blood flow in arteries or veins.

The present specification also discloses a method for generating an electrical signal for vascular stimulation, the method comprising: identifying a first electrical stimulation response threshold for vasoconstriction in a patient; identifying a second response threshold for thrombosis in the patient; and stimulating with electrical stimulation The signal electrically stimulates the vascular structure, the electrical stimulation signal being below the identified second response threshold for thrombosis and above the first response threshold for vasoconstriction, such that stimulation produces an advantage of vasoconstriction over thrombosis.

This specification also discloses a method of controlling blood flow to an organ by arranging at least one electrode of a stimulation device in electrical communication with an artery, vein, nerve supplying an artery or vein, or a wall of said body organ; The at least one electrode is connected to an electrical pulse generator; and the pulse generator is caused to generate electrical stimulation applied through the at least one electrode to the wall of the artery, vein, nerve or body organ, wherein the electrical stimulation is effective to change to The blood flow of the body organ, wherein the blood flow is maintained for at least 1 minute after the electrical stimulation is stopped.

The above summary of the present invention is not intended to describe each disclosed embodiment or every implementation of the present invention. The following description more specifically illustrates exemplary embodiments. However, embodiments other than those expressly described are possible and can be made, used and/or carried out in, used and/or under the same or different environments and/or conditions as those described in connection with the exemplary embodiments implement. In several places throughout the application, guidance is provided through a collection of examples, which examples can be used in various combinations. In each case, the enumerated list serves only as a representative group and should not be construed as an exclusive list.

The foregoing and other embodiments of the present specification are described in greater detail in the accompanying drawings and detailed description provided below.

Brief Description of Drawings

These and other features and advantages of the present invention will be further understood as they will become better understood by reference to the detailed description when considered in conjunction with the accompanying drawings:

Figure 1 is a schematic representation of a portion of the mesenteric vasculature.

2 is a schematic diagram of an exemplary electrode set implanted in the celiac artery.

3 is a schematic diagram of an exemplary electrode set implanted in the superior mesenteric vessel.

4 is a schematic diagram of an exemplary electrode set implanted in the inferior mesenteric vessel.

5 is a schematic diagram of an exemplary infusion system implanted in the mesenteric circulation.

Figure 6 shows an exemplary form and configuration of electrodes used in the methods disclosed herein;

Figure 7A depicts graphs showing femoral vasoconstriction in response to stimulation as a function of normalized diameter and pulse amplitude;

Figure 7B depicts graphs showing constriction of femoral vessels in response to stimulation as a function of pulse amplitude and pulse duration;

Figure 7C depicts a graph showing constriction of mesenteric vessels in response to stimulation as a function of pulse amplitude and pulse duration;

Figure 8A shows graphs showing blood loss from the femoral artery with and without the application of electrical stimulation.

Figure 8B shows graphs showing blood loss from mesenteric arteries with and without electrical stimulation.

Figure 8C shows a graph showing vasoconstriction when electrical stimulation was applied for 100 μsec at a frequency of 10 Hz.

Figure 8D shows a graph showing vasoconstriction when electrical stimulation was applied for 1 msec at a frequency of 10 Hz.

Figure 9A shows the arterial site of electrode application corresponding to the organ being operated on;

Figure 9B shows the venous site of electrode application corresponding to the organ being operated on;

Figure 10A shows an exemplary card skin electrode for providing electrical stimulation in accordance with various embodiments of the present specification;

Figure 10B shows another exemplary card skin electrode for providing electrical stimulation according to various embodiments of the present specification;

FIG. 10C shows another exemplary card skin electrode for providing electrical stimulation according to various embodiments of the present specification;

Figure 10D shows yet another exemplary card skin electrode for providing electrical stimulation according to various embodiments of the present specification;

Figure 11 shows an exemplary clamp electrode for providing electrical simulation to a blood vessel according to various embodiments of the present specification;

Figure 12 shows a laparoscopic forcep for applying a clamp electrode to a blood vessel according to an embodiment of the present specification.

Figure 13A shows an electrode for placement within a laparoscopic catheter within a blood vessel according to an embodiment of the present specification;

Figure 13B shows an expanded electrode extending from a catheter of a laparoscope for placement within a blood vessel, according to an embodiment of the present specification;

Figure 14A shows a blood vessel pierced by a catheter having a stimulation electrode disposed inside, according to an embodiment of the present specification;

Figure 14B shows the catheter of Figure 14 with electrodes extending from the catheter;

Figure 14C shows the electrode of Figure 14 in contact with the inner wall of a blood vessel;

Fig. 14D shows the electrode of Fig. 14 connected by a wire to the implantable pulse generator;

Figure 14E shows electrical stimulation applied to a femoral artery with an obstruction in a human leg, according to embodiments of the present specification;

Figure 14F shows an arterial implant applied after arterial vasoconstriction in a human leg, according to embodiments of the present specification;

Figure 14G shows the arterial and venous structure of blood vessels in the human leg;

14H shows a catheter with an expandable electrode covering an expandable balloon positioned within a blood vessel, according to an embodiment of the present specification;

Figure 14I shows the electrode and balloon of Figure 14H extended from the catheter and inflated due to inflation/inflation of the intravascular balloon;

Figure 14J shows the electrodes of Figure 14H connected by wires to the implantable pulse generator;

Figure 15A shows the application of electrical stimulation to the uterine artery to prevent uterine bleeding according to an embodiment of the present specification;

Figure 15B shows the application of electrical stimulation to the uterine wall to prevent uterine bleeding according to an embodiment of the present specification;

Figure 15C shows the application of electrical stimulation to the wall of the uterine cavity to prevent uterine bleeding according to another embodiment of the present specification.

Figure 15D shows an expandable balloon catheter with expandable electrodes for controlling bleeding, according to an embodiment of the present specification.

Figure 16 shows a method of treating a tumor by applying electrical stimulation according to an embodiment of the present specification;

Figure 17A shows a segment of a human liver;

Figure 17B shows a lobe of a human liver;

Figure 17C shows control of hepatic hemorrhage by applying electrical stimulation according to an embodiment of the present specification;

Figure 17D shows control of hepatic hemorrhage by applying electrical stimulation according to another embodiment of the present specification;

FIG. 18A shows an anchor for holding an electrode lead within a blood vessel according to one embodiment of the present specification;

Figure 18B shows an anchor for maintaining a lead within a blood vessel according to another embodiment of the present specification;

19A shows a surgical device having articulating jaws operable as a pincer protruding from a tip opening of an endoscopic catheter proximate a bleeding vessel, according to an embodiment of the present specification;

Figure 19B shows electrical stimulation applied to a blood vessel through the articulating jaws of Figure 19A;

Figure 20A shows a site in a human body for implantation of an active or passive wireless microdevice to deliver electrical stimulation to a blood vessel in accordance with embodiments of the present specification;

Figure 20B shows an exemplary implantable microdevice for delivering electrical stimulation to a blood vessel according to embodiments of the present specification;

Figure 20C shows an exemplary handheld remote control device for activating an implanted microdevice to deliver electrical stimulation to a blood vessel, according to embodiments of the present specification;

Figure 20D shows another exemplary handheld remote control device for activating an implanted microdevice to deliver electrical stimulation to a blood vessel according to another embodiment of the present specification;

Figure 20E shows an exemplary implantable microdevice for delivering electrical stimulation to a blood vessel according to embodiments of the present specification;

20F shows an exemplary circuit diagram of an implantable microdevice for delivering electrical stimulation to a blood vessel, according to embodiments of the present specification;

Figure 20G shows another exemplary implantable microdevice for delivering electrical stimulation to a blood vessel according to another embodiment of the present specification;

Figure 21 is a flowchart showing steps for regulating blood flow by applying electrical stimulation to a blood vessel, according to embodiments of the present specification.

Figure 22A shows stimulation provided to a blood vessel in a patient's upper extremity to control bleeding downstream of the stimulation site, in accordance with embodiments of the present specification;

Figure 22B shows stimulation provided to a blood vessel in a patient's upper extremity to control bleeding downstream of the stimulation site, according to another embodiment of the present specification;

Figure 23 shows stimulation provided to blood vessels in a patient's lower extremities to control bleeding downstream of the stimulation site, according to embodiments of the present specification;

Figure 24 shows stimulation provided to blood vessels in a patient's abdomen to control bleeding downstream of the stimulation site, according to embodiments of the present specification;

Figure 25 is a flowchart showing steps for controlling bleeding in a patient's upper or lower extremity by applying electrical stimulation to blood vessels upstream of the bleeding site, according to embodiments of the present specification;

26A is a flowchart showing steps for preventing and/or controlling bleeding in a patient during abdominal surgery by applying electrical stimulation to blood vessels upstream of a potential bleeding site, according to one embodiment of the present specification.

26B is a flowchart showing steps for preventing anticipated bleeding in a patient during abdominal surgery by applying electrical stimulation to blood vessels upstream of a potential bleeding site, according to embodiments of the present specification; and

Figure 27 is a flow chart showing the steps of positioning a stimulation site on the skin surface and providing electrical stimulation to control bleeding in accordance with embodiments of the present specification.

Detailed description of the invention

The present invention provides methods of treating gastrointestinal (GI) disorders. Typically, treatment involves controlling the function of the gastrointestinal system by regulating blood flow through the tissues and organs of the gastrointestinal tract. Typically, control of blood flow through the GI tract is accomplished by applying stimulation to the blood vessels supplying the GI tract or the nerves that control those blood vessels.

This specification refers to various embodiments. The following disclosure is provided to enable those of ordinary skill in the art to practice the present invention. Language used in this specification should not be construed as a general disavowal of any one specific embodiment, or used to limit the claims beyond the meaning of the terms used therein. The general principles defined herein may be applied to other embodiments and applications without departing from the spirit and scope of the invention. Also, the terminology and phraseology used is for the purpose of describing the exemplary embodiments and should not be regarded as limiting. Therefore, the present invention is to be accorded the broadest scope encompassing numerous alternatives, modifications and equivalents consistent with the principles and features disclosed. For the purpose of clarity, details of technical material that is known in the technical fields related to the invention have not been described in detail so as not to unnecessarily obscure the invention.

"Treatment," "treating," and variations thereof refer to any reduction in the extent, frequency, or severity of one or more symptoms or signs associated with a condition.

"Duration" and variations thereof refer to the time course of a prescribed treatment from start to finish (whether treatment ends because the condition has resolved or treatment is discontinued for any reason). During treatment, multiple treatment sessions can be prescribed during which one or more prescribed stimuli are administered to the subject.

"Period" refers to the time during which a "dose" of stimulation is administered to a subject as part of a prescribed treatment plan.

The term "and/or" refers to one or all of the listed elements or a combination of any two or more of the listed elements.

In the specification and claims of this application, each of the words "comprising", "including" and "having" and their forms are not necessarily limited to the members of the list to which the word may be associated. It should be noted herein that any feature or component described in connection with a particular embodiment can be used and performed with any other embodiment, unless expressly stated otherwise.

Unless stated otherwise, "a," "an," "the/the," "one or more," and "at least one" are used interchangeably and mean one or more than one /kind.

For any method disclosed herein that includes discrete steps, the steps can be performed in any practicable order. Also, where appropriate, any combination of two or more steps may be performed simultaneously.

Also, herein, the recitation of numerical ranges by endpoints includes all numbers subsumed within that range (eg, 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, etc.). Unless otherwise indicated, all numbers used in the specification and claims indicating component amounts, molecular weights, etc. should be understood to be modified in all instances by the term "about". Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and claims are approximations that can vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. All numerical values, however, inherently contain ranges necessarily resulting from the standard deviation found in their respective testing measurements.

appetite regulation

The mesenteric blood supply is important for the proper functioning of the gastrointestinal system and for the digestion of all nutrients. Disruption of the mesenteric vascular supply can impair the digestion of various nutrients, including fat digestion, and thus can aid in the management of hypernutrient conditions, including, for example, obesity.

Reference is now made to the various views of the accompanying drawings. FIG. 1 shows a portion of the gastrointestinal (GI) tract, including celiac artery 11 , superior mesenteric artery 12 , inferior mesenteric artery 13 , internal iliac artery 16 , external iliac artery 17 , superior mesenteric vein 18 , and inferior mesenteric vein 19 . As used herein, the term "mesenteric artery" refers collectively to the celiac artery 11 , the superior mesenteric artery 12 and the inferior mesenteric artery 13 . Also, the term "mesenteric vein" refers collectively to the superior mesenteric vein 18 and the inferior mesenteric vein 19.

The mesenteric artery constitutes the major arterial blood supply to the gastrointestinal system, and the mesenteric vein constitutes the major system for draining blood from the gastrointestinal system. The flow of blood into and out of the gastrointestinal system is controlled by the tight contraction and relaxation of smooth muscles in the vessels of the mesenteric vasculature. Blood flow in the fasted state maintains the vitality of the gastrointestinal tract. In the fed state, the work of the gastrointestinal tract increases, and the demand for oxygen and nutrients to the gastrointestinal system increases accordingly. The increased demand for oxygen and nutrients is met by increasing blood supply to the gastrointestinal tract (achieved by dilation of the mesenteric arteries). This phenomenon of increased gastrointestinal energy demand after eating is called food-specific dynamics. In cases of dehydration or bleeding, blood is shunted from the gastrointestinal tract to other vital organs. This reduction in blood supply to the gastrointestinal tract is achieved by constriction of the mesenteric arteries. Subjects with blockages in the mesenteric arteries due to, for example, atherosclerotic arterial disease may have difficulty increasing blood supply to the gastrointestinal tract, which is required for postprandial processing and digestion of food. These subjects can develop pain, anorexia, and weight loss.

The methods described herein relate to controlling appetite, inducing satiety and/or inducing weight loss in a subject via stimulation of the mesenteric vasculature and/or nerves supplying the mesenteric vasculature, by modulating blood flow to the gut and more specifically It does so by modulating a specific dynamic effect of food (ie, a meal-induced increase in blood supply to the gastrointestinal tract).

The methods described herein may also be applied to treat certain cardiovascular conditions or indications, including angina, chest tightening, unstable angina, stable angina, coronary artery disease, atherosclerotic disease, heart failure or myocardial infarction. The present invention may also aid in the treatment of the aforementioned cardiovascular conditions by reducing blood flow to the gut and, more particularly, by minimizing the increase in blood flow to the gastrointestinal tract due to the specific dynamic effects of food. Specifically, reducing blood flow in the mesenteric or peripheral circulation of a patient increases blood flow in the coronary or cerebral circulation, thereby reducing or eliminating symptoms associated with the aforementioned disorders.

To reduce meal-induced blood flow to the gastrointestinal tract, electrical, chemical or mechanical stimulation effective to treat gastrointestinal conditions is applied to the celiac artery 11, superior mesenteric artery 12, inferior mesenteric artery 13, internal iliac artery 16, external iliac artery 17. Superior mesenteric vein 18 or inferior mesenteric vein 19, or nerve 15 supplying celiac artery 11, superior mesenteric artery 12, inferior mesenteric artery 13, internal iliac artery 16, external iliac artery 17, superior mesenteric vein 18 or inferior mesenteric vein 19 one or more target locations. As used herein, a stimulus "effective to treat a gastrointestinal condition" includes stimulation sufficient to cause, for example, the celiac artery 11 , superior mesenteric artery 12 , inferior mesenteric artery 13 , internal iliac artery 16 , external iliac artery 17 , superior mesenteric vein 18 or inferior mesenteric vein 19 At least one or more of the contractions are stimulated, thereby reducing blood flow into the gastrointestinal tract.

Reduced blood flow to the gastrointestinal tract can disrupt gastrointestinal functions, such as digestion and absorption of nutrients, such as fats. Stimulation may result in suppression of appetite in the subject and/or induce satiety, anorexia, and/or weight loss in the subject due to discomfort caused by the patient upon ingestion and thus stimulation of the target site. Thus, in certain embodiments, stimulation "effective to treat a gastrointestinal condition" may include stimulation, which may, for example, suppress appetite in a subject and/or induce satiety, anorexia, and/or weight loss in a subject . In other embodiments, stimulation "effectively treating a gastrointestinal condition" may include effective treating conditions secondary to obesity, such as, for example, diabetes, hypertension, heart attack, stroke, dyslipidemia, sleep apnea, Pickwick ( Pickwickian syndrome, asthma, lower back and disc disease, weight-bearing osteoarthritis of the hip, knee, ankle and foot, thrombophlebitis and pulmonary embolism, abrasion dermatitis, stress urinary incontinence, gastroesophageal reflux disease (GERD) , gallstones, cirrhosis, liver cancer, infertility, uterine cancer and/or breast cancer stimulation.

In one embodiment, at least one electrode set is placed in the celiac artery 11 , superior mesenteric artery 12 , inferior mesenteric artery 13 , internal iliac artery 16 , external iliac artery 17 , superior mesenteric vein 18 or inferior mesenteric vein 19 or celiac artery 11 In the mesenteric circulation near one or more of the branches, superior mesenteric artery 12, inferior mesenteric artery 13, internal iliac artery 16, external iliac artery 17, superior mesenteric vein 18, or inferior mesenteric vein 19. Each electrode set includes at least one active electrode and at least one ground electrode. The electrode set can be connected to the celiac artery 11, the superior mesenteric artery 12, the inferior mesenteric artery 13, the internal iliac artery 16, the external iliac artery 17, the superior mesenteric vein 18 or the inferior mesenteric vein 19, or the branch of the celiac artery 11, the superior mesenteric artery 12 , inferior mesenteric artery 13, internal iliac artery 16, external iliac artery 17, superior mesenteric vein 18, or inferior mesenteric vein 19 to produce any pattern of desired stimulation, eg, circumferential pattern, along longitudinal axis, irregular pattern, or other placement.

In a preferred embodiment, the celiac artery or a branch of the celiac artery is stimulated by itself or in combination with at least one other vascular structure. In another preferred embodiment, the celiac artery or a branch of the celiac artery is stimulated in combination with the SMA or a branch of the SMA. In another preferred embodiment, at least two vascular structures, such as arteries, veins or nerves associated with arteries or veins, are stimulated simultaneously or in a predetermined order or a combination of both. The predefined sequence can be fast or slow sequential.

FIG. 2 shows an embodiment in which an electrode set 21 is placed in the celiac artery 11 in a loose linear configuration. The device containing the pulse generator 26 transmits a signal that causes the electrode set 21 to deliver electrical stimulation to the celiac artery 11 . The device 26 is connected to a power source 28 for providing power. The device 26 is further connected to the electrode set 21 by wires 20 to transmit electrical stimulation signals to the electrode set 21 . Alternatively, electrode set 21 may be wirelessly coupled to device 26 using radio frequency (RF) connections, ultrasonic connections, thermal connections, magnetic connections, electromagnetic connections, or optical connections. Stimulation of the celiac artery 11 by the electrode set 21 can induce vasoconstriction of the celiac artery 11, which in turn can reduce the blood supply to the upper gastrointestinal tract. US Patent Application Serial No. 12/359,317, filed January 25, 2009, which is incorporated herein by reference in its entirety, may be used for all embodiments of the invention disclosed in this application.

In some embodiments, the stimulator device 26 may be manually triggered by, for example, a medical professional, caregiver, or subject. Alternatively, a set of sensing electrodes 24 can detect one of the physiological parameters associated with a meal and generate a signal to deliver electrical stimulation to the celiac artery 11, which can cause meal-induced vasoconstriction in the abdominal cavity, thereby suppressing the subject's appetite and/or Induce anorexia, satiety and/or weight loss in the subject. Exemplary physiological parameters are identified below.

FIG. 3 shows another embodiment in which an electrode set 21 is placed on one of the superior mesenteric artery 12 or the superior mesenteric vein 18 . The first and second devices including the pulse generators 36, 36' are connected to the first and second power sources 38, 38' to provide power. The devices 36, 36' are further connected to the electrode set 21 by wires 30 as previously described. Alternatively, the electrode set 21 may be wirelessly coupled to the devices 36, 36', as previously described. The stimulation electrode 21 can stimulate the superior mesenteric artery 12 to cause vasoconstriction of the superior mesenteric artery 12 or stimulate the superior mesenteric vein 18 to cause the superior mesenteric vein vasoconstriction, thereby reducing blood supply to the middle portion of the gastrointestinal system.

In some embodiments, the stimulator device 36, 36' may be manually triggered by, for example, a medical professional, caregiver, or subject. Alternatively, a set of sensing electrodes 34 may detect one of the physiological parameters associated with a meal and generate a signal to cause vasoconstriction of the superior mesenteric artery 12 or superior mesenteric vein 18 and reduce blood supply to the middle portion of the gastrointestinal system. This can induce feelings of satiety, satiety, and/or loss of appetite.

FIG. 4 shows another embodiment in which an electrode set 21 is placed in one of the inferior mesenteric artery 13 or the inferior mesenteric vein 19 . The first device containing the pulse generator 46 is connected to a power source 48 for providing power. The device 46, 46' Alternatively, the electrode set 21 may be wirelessly coupled to the devices 46, 46'. One of the devices 46, 46' may control an electrode set 21. Alternatively, one of the devices 46, 46' may control more than one electrode set. The stimulation electrode 21 can stimulate the inferior mesenteric artery 13 or the inferior mesenteric vein 19, causing vasoconstriction and reducing blood supply to the lower gastrointestinal system.

In some embodiments, the stimulator device 46, 46' may be manually triggered by, for example, a medical professional, caregiver, or subject. Alternatively, a set of sensing electrodes 44 can detect one of the physiological parameters associated with the meal and generate a signal to cause the delivery of electrical stimulation that can cause vasoconstriction of the inferior mesenteric artery 13 or inferior mesenteric vein 19 and reduce the pressure on the inferior The blood supply of the gastrointestinal system.

In each of the above embodiments, the blood supply to the gastrointestinal (GI) system is reduced (whether to the upper GI system as eg depicted in FIG. 2 , the intermediate GI system as eg depicted in FIG. The lower GI system depicted in ) can suppress appetite in a subject and/or induce anorexia, satiety, and/or weight loss in a subject. In one embodiment, the patient consumes 5% or more (eg, 10%, 20%, 30%, 40% less) if relative to the patient's historical average daily, weekly, monthly, quarterly or annual calorie intake , 50%, 60%, 70%, etc.) calories, it is considered to suppress the subject's appetite or induce satiety. In another embodiment, a subject is considered to be appetite-suppressed or induced if the patient consumes less than a threshold number of maximum calories relative to the patient's historical average daily, weekly, monthly, quarterly or annual calorie intake Satiety, where a threshold number of maximum calories is defined based on the patient's desired weight loss goal. In another embodiment, a subject causes substantial weight loss if the subject has lost at least 30% of the subject's excess weight (calculated by subtracting the target weight from the subject's current weight). In another embodiment, the subject causes a substantial Weight loss.

Also in each embodiment, the electrode set 21 can provide electrical stimulation from about 1 microamp (μAmp) to about 100 Amp, although the methods described herein can be practiced by providing electrical stimulation outside of this range. Typically, the amplitude of the electrical stimulation can range from about 1 milliamp (mAmp) to about 10 Amp. In some embodiments, the electrical stimulation may be less than about 10 Amp, such as, for example, less than 1 Amp. In certain embodiments, the amplitude of the electrical stimulation may be from about 5 mAmp to about 100 mAmp, such as, for example, 10 mAmp. Also, certain treatments may include multiple electrical stimulations with any combination of different amplitudes.

Electrical stimulation "dose" may be delivered continuously or intermittently. For example, electrical stimulation may be provided at one time, may be provided continuously for a specified period of time, or may be provided in a series of intermittent stimulation over a specified period of time. The prescribed period of time may be, for example, about 1 millisecond (msec) to about 1 hour. Intermittent electrical stimulation may be provided at regular prescribed intervals during the treatment period. For example, intermittent electrical stimulation of 1 second in length can be provided for, eg, 1 hour. In other cases, intermittent electrical stimulation may be provided "as needed." Also, certain treatments may include multiple electrical stimulations delivered through any combination of different treatment periods.

The electrical stimulation can have any pattern necessary to produce the desired result, including square, rectangular, sinusoidal, or sawtooth. Also, certain treatments may include multiple electrical stimulations, including any combination of modalities.

The frequency of electrical stimulation may be in the range of about 1 microhertz (μHz) to about 1 megahertz (MHz), although the methods described herein may be practiced by administering electrical stimulation at frequencies outside this range. Typically, electrical stimulation may have a frequency of about 1 mHz to about 1 MHz, such as, for example, a frequency of about 0.1 Hz to about 10 Hz. In certain embodiments, electrical stimulation may be administered at a frequency of about 1 Hz. Also, certain treatments may include multiple types of electrical stimulation, including any combination of frequencies.

The electrodes of the electrode set 21 can be placed on the intima, blood vessels of the celiac artery 11, the superior mesenteric artery 12, the inferior mesenteric artery 13, the internal iliac artery 16, the external iliac artery 17, the superior mesenteric vein 18 and/or the inferior mesenteric vein 19. In the media, adventitia and/or adventitia of blood vessels. Alternatively, the electrodes of electrode set 21 may be placed in the supply celiac artery 11, superior mesenteric artery 12, inferior mesenteric artery 13, internal iliac artery 16, external iliac artery 17, superior mesenteric vein 18 and/or inferior mesenteric vein 19 or celiac artery 11. On nerves 15 of branches of superior mesenteric artery 12, inferior mesenteric artery 13, internal iliac artery 16, external iliac artery 17, superior mesenteric vein 18 and/or inferior mesenteric vein 19. Alternatively, the electrodes of electrode set 21 may be placed on nerves 15 supplying celiac artery 11 , superior mesenteric artery 12 , inferior mesenteric artery 13 , internal iliac artery 16 , external iliac artery 17 , superior mesenteric vein 18 and/or inferior mesenteric vein 19 superior. The number of electrodes in a set and the number of sets of electrodes used to treat a particular condition can be affected by factors such as, for example, the size of the electrodes, the prescribed stimulation amplitude, frequency and/or pattern, and the size of the desired placement area.

Figure 6 shows exemplary electrode designs, configurations and arrangements including, for example, loose linear 6A, extravascular coil 6B, patch 6C, intravascular coil 6D, hook 6E and circumferential 6F electrodes.

Electrical stimulation can be triggered by a transmitter external to the body, similar to the remote transmitter of a cardiac pacemaker. With appropriate stimulation amplitude, frequency and pattern, and appropriate treatment period and duration, gastrointestinal disorders such as obesity can be treated without permanent damage to surrounding tissues or organs.

Figure 5 shows another embodiment in which an infusion catheter 51 is placed in one or more of the celiac artery 11, the superior mesenteric artery 12, or the superior mesenteric vein 18 for delivering chemical stimulation rather than electrical stimulation. The device containing the infusion pump 56 is connected to a reservoir 58, which can supply a vasoactive or neuroactive chemical. The infusion catheter 51 may deliver vasoactive or neuroactive chemicals to the celiac artery 11, the superior mesenteric artery 12, or one of the superior mesenteric vein 18 or the inferior mesenteric vein 19 to modify the flow of vasoactive or neuroactive chemicals to and/or from the gastrointestinal tract. blood flow. This can lead to gastrointestinal ischemia or congestion.

Figure 5 also shows an embodiment in which an infusion catheter 53 is placed in one or more of the inferior mesenteric artery 13 or the inferior mesenteric vein 19 to deliver chemical stimulation rather than electrical stimulation. The device containing the infusion pump 55 is connected to a reservoir 57, which can supply a vasoactive or neuroactive chemical. Infusion catheter 53 may deliver vasoactive or neuroactive chemicals to one of inferior mesenteric artery 13 or inferior mesenteric vein 19 to modify blood flow to and/or from the gastrointestinal tract. This can lead to gastrointestinal ischemia or congestion.

Chemical stimulation "dose" may be provided continuously or intermittently. For example, chemical stimulation may be provided at one time, may be provided continuously for a specified period of time, or may be provided in a series of intermittent stimulation over a specified period of time. The prescribed period of time may be such as, for example, about 0.1 μL/hr to about 1 L/min, such as, for example, 0.1-10 μL/min. Intermittent chemical stimulation may be provided at regular prescribed intervals during the treatment period. For example, intermittent chemical stimulation can be provided at a rate of 0.1 μL/min for 30 minutes. In other cases, intermittent chemical stimulation may be provided "as needed." Also, certain treatments may include multiple chemical stimuli provided by any combination of different treatment periods.

In some embodiments, the signal to deliver the vasoactive or neuroactive chemical can be manually triggered by, eg, a medical professional, caregiver, or subject. Alternatively, a set of sensing electrodes can detect one of the physiological parameters associated with the meal and generate a signal to cause the delivery of a chemical stimulus, which can affect the blood supply to the gastrointestinal tract. However, the signal that triggers the delivery of the vasoactive or neuroactive chemical can modulate the volume, frequency and/or pattern of the vasoactive or neuroactive chemical delivered and the time and/or duration of chemical stimulation. The prescribed chemical stimulus can suppress appetite and/or induce anorexia, satiety, and/or weight loss in the subject.

Chemical stimulation can be triggered by a transmitter outside the body, which is similar to a pacemaker's remote transmitter. With appropriate dosage, frequency and pattern, and appropriate period and duration of treatment, gastrointestinal disorders such as obesity can be treated without permanent damage to surrounding tissues or organs.

Stimulation (whether continuous or intermittent, electrical or chemical) can be used to modulate the smooth muscle of the mesenteric vasculature over time. With sufficient tone, further irritation can be reduced or eliminated. Thus, gastrointestinal disorders can be successfully treated using treatments of different durations. For example, certain conditions may be successfully treated with a single treatment, while other conditions may require more prolonged treatment, such as, for example, one week, 1 month, 6 weeks, 1 year, or, in some cases, may require long-term (including, for example, life) )treat.

Referring concurrently to FIGS. 2-4 , in some embodiments, the devices 26 , 36 , 46 , 56 may be controlled by the microprocessors 22 , 32 , 42 , 52 . In some embodiments, the microprocessor 22, 32, 42, 52 may be operably connected to the signal generator and may be programmed to control the signals generated by the devices 26, 36, 46, 56 during various treatment sessions and/or durations The length, power, and frequency of the resulting electrical signal. In other embodiments, the microprocessor 22, 32, 42, 52 may be operably connected to the pump and may be programmed to control the generation of the device 26, 36, 46, 56 during various treatment sessions and/or durations The length, volume and frequency of the chemical signal.

In an exemplary embodiment, a subject may use a remote-controlled RF signaling device to signal meal intake. Based on the subject's desired weight loss, a microprocessor implanted in the signal-generating device may send multiple trains of pulses after a preset time delay. In the case of, for example, a male subject who desires a 150-pound weight loss and a 1000-calorie-a-day diet is recommended, the preset time to start mesenteric vascular stimulation may be 10 minutes from the start of eating. Typical stimulation parameters may have, for example, a burst of 6 rectangular pulses with a duration of eg 2 msec and a pulse amplitude of eg 10 mAmp. The duration of each single burst of 6 pulses may be eg 200 msec and have a frequency of eg 1 burst per second. The pulse train may be interrupted by a quiescent period of eg 800 msec. For example, the quiescent phase may allow for repolarization of the mesenteric vascular musculature. The pulse train can induce, for example, constriction of the celiac and superior mesenteric arteries, resulting in a physiological blockage of blood flow to the stomach and intestines. This can cause discomfort and/or pain, leading to premature saturation and/or anorexia in the subject.

Stimulation can continue until the subject stops eating, after which the stimulation ceases. Alternatively, a sensor can be implanted in the gastrointestinal tract, which senses food intake and triggers a microprocessor, which in turn triggers a signal generator to deliver stimulation to the abdominal cavity and superior mesenteric artery. The sensor can also detect the end of ingestion and transmit a shutdown signal to the microprocessor, which in turn will shut down the stimulator.

Based on the subject's continued caloric restriction, the subject's physician can adjust the stimulation mode using an external remote control without additional surgery. After the desired weight loss is achieved, the stimulator can be turned off remotely, and if the subject begins to regain weight, the stimulator can be turned on remotely.

In certain embodiments, the methods described herein can be implemented using a neural stimulation system having at least one electrode set, at least one power source, and an extension connecting the power source to the electrode set. Electrodes can be integrated into wires, where wires are small conductors in which more than one electrode is integrated. In one embodiment, surgically implanted leads may be used, including, for example, the 3587A RESUME II lead, 3986RESUME TL lead, 3998SPECIFY lead, 3999Hinged SPECIFY lead, 3982SYMMIX lead, and/or 3987On-Point PNS lead (all from Medtronic, Inc., Minneapolis, Minn.), or any other quadrupole lead with flat electrodes capable of creating a variety of stimulation combinations over a broad area of paresthesia.

In one embodiment, the devices 26, 36, 36', 46, 56 may be implantable battery-operated neurostimulators with non-invasive programmability, such as, for example, ITREL 3, SYNERGY, SYNERGYPLUS ⁺ , or SYNERGYCOMPACT ⁺ (All from Medtronic, Inc., Minneapolis, Minn.). Alternatively, the device 26, 46', 55 comprises a radio frequency (RF) system, which may include an implanted receiver from an external power source or transmitter such as a MATTRIX transmitter (Medtronic, Inc., Minneapolis, Minn.) Detects RF signals passing through the skin.

In another embodiment, the extension may be a small conductor that electrically connects the power source to the wire. Exemplary extensions include low profile, low impedance extensions and/or bifurcated, low profile, low impedance extensions.

As shown in Figures 2 to 4, the present invention may optionally include additional sensing electrodes 24, 34, 44, 54 placed in the gastrointestinal tract or near the nerves supplying the gastrointestinal tract or vascular system. The sensing electrodes 24, 34, 44, 54 may be capable of sensing one or more physiological stimuli such as, for example, esophageal peristalsis, esophageal pH, esophageal impedance, esophageal pressure, esophageal electrical activity, lower esophageal sphincter (LES) pressure, LES electrical Activity, gastric motility, gastric electroactivity, gastric chemical activity, gastric hormone activity, gastric temperature, gastric pressure, gastric impedance and gastric pH, duodenal peristalsis, duodenal electroactivity, duodenal chemical activity, ten Duodenal hormone activity, duodenal temperature, duodenal pressure, duodenal impedance and duodenal pH, blood chemical activity, blood hormone activity, vagal or other gastrointestinal neuroactivity, salivary chemical activity , bile pressure, biliary electrical activity, biliary chemical activity, pancreatic pressure, pancreatic electrical activity, pancreatic chemical activity, pancreatic sphincter pressure, pancreatic sphincter electrical activity, biliary sphincter pressure or biliary sphincter electrical activity, mesenteric vascular pressure, mesenteric vascular flow and/ or mesenteric vascular chemical content.

Upon sensing an appropriate physiological stimulus, the sensing electrodes 24, 34, 44, 54 may be directed to the devices 26, 36, 46, 56 via the wires or leads 29, 39, 49, 59 and the processors 22, 32, 42, 52 Transmission signal. The device 26 , 36 , 46 , 56 can then start, maintain, adjust or stop the electrical stimulation signal sent to the electrode set 21 . Thus, the methods described herein can be more responsive to the particular biological state of the subject and precisely modulate at least a portion of the mesenteric vasculature such that a portion or all of the mesenteric system can contract or relax to regulate blood flow into the gastrointestinal tract. Control of blood flow to the gastrointestinal tract can also be achieved by turning off the transmitter of an external pacemaker. As is known in the art, stimulation electrode set 21 may be used in combination with additional pacing electrodes to treat gastrointestinal motility or functional disorders. It should be understood that the sensing electrodes may be implemented in any embodiment of the present invention, including those shown in Figures 3-5.

Any stimulation or sensing electrode set can be placed by conventional surgery, laparoscopy, endoscopy, radiology or other minimally invasive vascular and surgical techniques to place the desired device or devices on the structure to be associated with it either near or in communication with the structure. Conventional electrode stimulation devices can be used to practice the methods described herein.

It will be appreciated that in the treatment of cardiovascular conditions such as angina pectoris, the period of stimulation may last much longer than in the treatment of conditions associated with inducing satiety or suppressing the subject's appetite. In one embodiment, the treatment of angina pectoris can be achieved by stimulating both the abdominal cavity and the SMA arteries simultaneously for several hours, such as 2, 3, 4, 5, 6 or more periods after a meal, as described above.

The invention is illustrated by the following examples. It is to be understood that the specific embodiments, materials, amounts and procedures are to be interpreted broadly in accordance with the scope and spirit of the invention as set forth herein.

Example 1

A mesenteric electrical stimulator was laparoscopically implanted in adult male subjects. The stimulator leads were implanted in the outer surface of the abdominal cavity and superior mesenteric artery, and the microcontroller was implanted in the pocket of the anterior abdominal wall.

Using a remote control signal, the microcontroller sends multiple bursts of 10 rectangular pulses after a preset time delay of 10 minutes from the start of the meal. The microcontroller delivered electrical stimulation with a pulse amplitude of 10 mAmp and a burst frequency of 2 bursts per second. The burst is interrupted by a quiescent period of 500 milliseconds (msec). Stimulation was performed until the patient stopped eating, after which time the stimulation was discontinued.

Example 2

In acute experiments, mesenteric vascular stimulation was implanted into the mesenteric vasculature of pigs. Stimulator leads were implanted on the outer surfaces of the celiac and superior mesenteric arteries and controlled by an external microcontroller. Typical stimulation parameters may have bursts of 10 pulses with a pulse amplitude of 20 mAmp and a burst frequency of 0.5 bursts per second. The duration of each burst of 10 pulses was 400 msec, with a resting phase of 1600 msec to allow repolarization of the mesenteric vascular muscle. The pulse train will induce constriction of the celiac and superior mesenteric arteries, resulting in a physiological blockage of blood flow to the stomach and intestines. The reduction in blood flow can be measured using a Doppler flowmeter.

Example 3

For chronic survival experiments, stimulators were implanted in the mesenteric vasculature of pigs. The stimulator leads were implanted on the outer surface of the abdominal cavity and superior mesenteric artery, and the microcontroller was implanted in a pocket in the anterior abdominal wall or worn on a jacket or belt. Typical stimulation parameters may have bursts of 10 pulses with a pulse amplitude of 10 mAmp, a duration of 400 msec and a burst frequency of 0.5 bursts per second. The burst is interrupted by a quiescent phase of 1600 msec to allow repolarization of the mesenteric vascular muscle. The stimulator was turned on and off randomly, and food intake during the on period was compared to the off period, demonstrating lower food and calorie intake when the stimulator was on. Additionally, the stimulator can be turned on continuously. Animals were allowed to eat freely. Serial body weight measurements showed less weight gain or weight loss compared to free-fed animals without the stimulator turned on.

Prevent, treat and/or control bleeding

In various embodiments, the present specification provides methods for regulating blood flow to treat bleeding or prevent expected bleeding. Typically, control of blood flow through arteries and veins is accomplished by applying stimulation to the blood vessels supplying blood or to the nerves that control those blood vessels. Blood vessels or nerves can be stimulated directly or indirectly. In various embodiments, one or more electrodes of the stimulation device are placed proximate an artery supplying blood to a body organ, a vein supplying blood from a body organ, a nerve supplying the artery or the vein, or the body the walls of organs, or communicate with them electrically. In various embodiments, proximate to or in electrical communication with is defined as being in electrical communication with a target artery supplying blood to a body organ, a vein supplying blood from a body organ, a nerve supplying said artery or said vein, or a The walls are locations with a distance ranging from 0 to 5 cm. In various embodiments, the location is also at least 1 cm upstream of the location on the vessel where the bleeding or bleeding is expected to occur. In other words, in various embodiments, the preferred stimulation site is at least 1 cm proximal or upstream of the injury or surgical site.

In one embodiment, the present specification provides a method of regulating blood flow to an organ by applying electrodes in close proximity to arteries, veins, or nerves supplying arteries and veins corresponding to the organ, and activating the electrodes to provide a constricting artery or vein. Electrical stimulation was performed. In various embodiments, providing electrical stimulation can be used to treat bleeding, control/stop bleeding, and treat tumors.

In some embodiments, the presently disclosed methods for treating, controlling, or preventing bleeding are practiced only in high-risk patients, including patients with liver disease, patients with coagulation disorders, or reliance on anticoagulant drugs, such as aspirin , Plavix, Coumadin and/or Xarelto. In some embodiments, the presently disclosed methods are performed in certain procedures with a higher risk of causing bleeding, including hepatobiliary surgery (which has a risk of hepatic artery and/or portal vein bleeding), splenectomy (which has a risk of bleeding from the portal vein) risk of bleeding from the splenic vein), vascular tumor resection (which has a risk of bleeding from the arteries supplying the tumor), Whipple procedure (which has a risk of bleeding from the pancreaticoduodenal artery), femoral-popliteal bypass (which has a risk of bleeding from the arteries supplying the tumor) risk of bleeding in the femoral artery) and aortic dissection (which carries the risk of bleeding in the aorta). The methods disclosed herein are practiced to minimize, prevent, control or treat bleeding that occurs in each of the arterial or venous locations listed above.

Microsecond or millisecond electrical pulses can induce vasoconstriction in both arteries and veins within seconds. Upon termination of stimulation, blood vessels dilate back to their original size within minutes. This reversible vasoconstriction can be repeated without causing any tissue damage. On stronger stimulation, a permanent blood clot can form, completely occluding the lumen of the blood vessel. Both reversible vasoconstriction and irreversible coagulation provide a powerful approach to bleeding prevention and/or control in non-compressible wounds. The degree of perfusion can be controlled by changing the amplitude, pulse duration, and pulse repetition rate.

The therapeutic basis of electrosurgery is the generation of heat at the cellular level. High frequency alternating current >100KHz (about 350KHz) flowing through the tissue generates heat, and a duty cycle of the current is used to create the desired tissue effect of cutting or coagulation. A temperature of 104°F resulted in reversible cell trauma, while a temperature of 120°F resulted in irreversible cell trauma. Higher temperatures lead to further changes in body tissue. For example, 158°F causes coagulation, 212°F causes cutting effects, and 392°F causes carbon cautery. However, stimulating tissue with lower frequency (<100KHz) currents produces neural stimulation without heat generation.

Conventional thermal coagulation of blood vessels typically requires tens of watts of power delivered by electrocautery or RF coagulators. Such techniques cause significant tissue damage and are not effective in coagulation of large vessels. Often, large vessels require mechanical ligation under direct visualization. Newer techniques such as Ligasure can heat seal larger arteries, but they require bulky power sources, good vessel visualization, and access to the vessel from all sides to accurately position the surgical probe, all of which prevent this technique from gaining traction in the field. use. Furthermore, due to the limitations of these techniques, there is a significant delay in bleeding control, resulting in significant blood loss before adequate bleeding control can be achieved, which in turn leads to the need for blood transfusions and associated risks.

In contrast, low-power (several mW) electrical vasoconstriction helps reduce blood flow without thermal damage to tissue, and may not require good visualization of damaged vessels to locate the tool. Since such stimulation requires very low power, a small disposable device, such as the one with electrodes described with reference to Figure 6, can be placed in the wound area to reduce or prevent local bleeding. A device may be placed before or during bleeding to prevent or treat bleeding. Furthermore, blood is a good electrical conductor, so perfect contact between electrodes and blood vessels may not be necessary for adequate bleeding control. Additionally, arteries, veins, or nerves remote from the injury site can be stimulated to achieve bleeding control. Temporary reductions in blood perfusion can be achieved within seconds using a reversible vasoconstriction protocol, with blood vessels dilating back to their original size within minutes after termination of stimulation. This modality can be used for non-destructive bleeding control during surgery as well as during trauma care. Permanent bleeding blockage is achieved when blood vessels constrict and then begin to clot. Additionally, therapy may be repeated multiple times to treat delayed bleeding from the site.

As described in the previous section of this specification, stimulation of blood vessels with current pulses induces local constriction of the femoral and mesenteric arteries and veins. It has been observed that each phase lasts 1 ms and that current biphasic (symmetric, anode-first rectangular) current pulses with an amplitude of 250 V and a repetition rate of 10 Hz result in very pronounced femoral and mesenteric arteries and veins within seconds. local shrinkage. Figure 7A shows the extent of femoral vasoconstriction in response to 10 second long stimulation at a repetition rate of 1 Hz as a function of stimulation amplitude and vessel diameter. Graph 702 shows constriction of the femoral artery, wherein: curve 704 represents constriction when stimulation is provided for 1 microsecond, curve 706 represents constriction when stimulation is provided for 10 microseconds, curve 708 represents constriction when stimulation is provided for 100 microseconds, And curve 710 represents the contraction when stimulation is provided for 1000 microseconds. Similarly, graph 712 shows contraction of the femoral vein, wherein: curve 714 represents contraction when stimulation is provided for 1 microsecond, curve 716 represents contraction when stimulation is provided for 10 microseconds, and curve 718 represents contraction when stimulation is provided for 100 microseconds , and curve 720 represents the contraction when the stimulus was provided for 1000 microseconds.

As can be seen from Figure 7A, for both arteries and veins, vasoconstriction increases with higher pulse amplitudes and longer durations. Further Figure 7A shows that vessel diameter decreases along a S-shaped curve with increasing pulse amplitude, with a response threshold at the lower end and reaching a minimum dimension of approximately 20-25% of the original diameter at the upper end. Figure 7B shows the degree of femoral vasoconstriction as a function of stimulation pulse amplitude and pulse duration. Curves 730 and 732 of graph 731 correspond to 25% and 50% contractions in the femoral artery, respectively. Curves 734 and 736 of graph 735 correspond to 25% and 50% contractions in the femoral artery, respectively. In various embodiments, the percent vasoconstriction of a blood vessel (eg, artery or vein) can be defined as the percent closure achieved by subtracting the stimulated constricted diameter from the unstimulated unconstructed diameter and dividing the difference It is calculated as the unstimulated, uncontracted diameter and can be measured using Doppler studies or angiograms or any other method known in the art.

As demonstrated by Figure 7B, the intensity-duration dependence of the 25% and 50% systolic thresholds can be approximated by a power dependence "t2a", where the value of "a" is about 0.3 for the femoral artery and vein . Furthermore, as shown in Figures 7A and 7B, for all pulse durations, lower voltages were required in arteries compared to veins to achieve similar contractions, although the difference decreased when stimulation was applied for longer durations.

Figure 7C shows the extent of mesenteric vasoconstriction in response to 10-second long stimulation at a repetition rate of 1 Hz as a function of stimulation amplitude and vessel diameter. Graph 742 shows constriction of the mesenteric artery, where curve 744 represents constriction when stimulation is provided for 1 microsecond, and curve 746 represents constriction when stimulation is provided for 100 microseconds. Similarly, graph 748 shows constriction of the mesenteric vein, where curve 750 represents constriction when stimulation is provided for 1 microsecond, and curve 752 represents constriction when stimulation is provided for 100 microseconds. Mesenteric vessels showed a similar kind of response to that of the femoral artery and vein. Vasoconstriction was higher in the mesenteric artery than in the femoral artery for the same pulse parameters, and the difference increased with larger amplitudes. For example, with a 1 μs pulse at 200 V, the mesenteric artery constricted by 76% compared to a 49% reduction in the femoral artery. Mesenteric veins contracted more than femoral veins at low amplitudes, and this ratio reversed at higher amplitudes.

In the experimental setup, the femoral and mesenteric arteries of the test subjects were dissected and some of these were then electrically stimulated. Experiments demonstrate that blood loss from a dissected artery subjected to electrical stimulation of a predefined amplitude for a predefined period of time is much less than blood loss from an untreated dissected artery. Figure 8A shows graphs showing blood loss from the femoral artery with and without the application of electrical stimulation. Curve 802 represents blood loss when the dissected femoral artery is not treated with electrical stimulation. Curve 804 represents a cut femoral artery stimulated with a 100 microsecond pulse of 30V for 30 seconds at 1 Hz, and curve 806 represents a cut femoral artery stimulated with a 100 microsecond pulse of 150V for 30 seconds at 10 Hz. Figure 8B shows graphs showing blood loss from mesenteric arteries with and without electrical stimulation. Curve 808 represents blood loss when the severed mesenteric artery was not treated with electrical stimulation, and curve 810 represents the severed mesenteric artery stimulated with 100 microsecond pulses of 40V for 30 seconds at 1 Hz. In both vessel types, treatment resulted in reduced or even complete cessation of post-stimulation bleeding, whereas continuous bleeding was observed in untreated arteries.

Figure 8C shows a series of graphs showing vasoconstriction when electrical stimulation was applied at a frequency of 10 Hz for 200 microseconds. Curve sets 820, 822, 824, and 826 show constriction of the mesenteric artery, mesenteric vein, ileo-femoral artery, and ileo-femoral vein, respectively. As shown, when no voltage was applied, ie, baseline voltage, there was no constriction in any of the vessels and they were 100% open. When the applied voltage was increased at 10V-50V intervals in the range of 0V to 100V, the blood vessels contracted stably. Thus, the graph shows that the constriction of the blood vessel increases as the applied voltage is increased. Also, it can be seen from Figure 8C that the application of voltage induces a greater degree of constriction in the mesenteric arteries and veins 820, 822 compared to the ileo-femoral arteries and veins 824, 826.

Figure 8D shows a series of graphs showing vasoconstriction when electrical stimulation was applied for 1 ms at a frequency of 10 Hz. Curve sets 830, 832, 834, and 836 show constriction of the mesenteric artery, mesenteric vein, ileo-femoral artery, and ileo-femoral vein, respectively. As shown, when no voltage was applied, ie, baseline voltage, there was no constriction in any of the vessels and they were 100% open. When the applied voltage was increased in the range of 0V to 100V in 10V-50V intervals, the blood vessels contracted more and more steadily. Thus, the graph shows that the constriction of the blood vessel increases as the applied voltage is increased. Also, it can be seen from FIG. 8D that the application of voltage induces a greater degree of constriction in the mesenteric arteries and veins 830, 832 compared to the ileo-femoral arteries and veins 834, 836. Similar results can be achieved by stimulating the carotid artery or its branches, the subclavian artery or vein or its branches, the jugular vein or its branches, or any other artery or vein or nerve supplying the artery or vein.

In various embodiments, electrodes such as, but not limited to, those described with reference to FIG. 6 can be used to provide stimulation to blood vessels to treat bleeding conditions. Electrodes can also be used to apply electrical stimulation to control blood loss during surgery on body organs. In various embodiments, the electrical stimulation provided to the vessel, nerve, or organ wall has a pulse duration in the range of 1 μsec-500 msec, a pulse amplitude in the range of 1 V-250 V, and a pulse frequency in the range of 1 Hz-100 kHz. In various embodiments, a system for treating bleeding includes at least one electrode in communication (wired or wireless) with a pulse generator. Optionally, the system also includes a microprocessor operably connected to the IPG that controls stimulation parameters generated by the IPG and applied by the at least one electrode.

Figure 9A shows the arterial site of electrode application corresponding to the organ being operated on. Blood supply to the stomach, duodenum, gallbladder, and liver through the celiac artery or branches of the celiac artery; blood supply to the pancreatic head through the celiac artery and the superior mesenteric artery or branches of the celiac artery or the superior mesenteric artery; through the superior mesenteric artery or branches of the superior mesenteric artery supply blood to the jejunum and ileum and appendix; supply blood to the colon through the superior mesenteric artery, inferior mesenteric artery, or branches of the superior or inferior mesenteric artery; supply blood to the spleen through the splenic artery or branches of the splenic artery; supply blood to the spleen through the renal, common iliac, internal iliac, or The renal arteries, the common iliac arteries, and the branches of the internal iliac arteries supply blood to the genitourinary system. Thus, electrodes can be placed in the left gastric artery 902 to provide electrical stimulation to constrict the blood vessel and regulate blood flow to adjacent portions of the stomach and esophagus, and the splenic artery 904 to provide electrical stimulation to constrict the blood vessel and regulate blood flow Spleen, stomach and pancreas; placed in common hepatic artery 906 to provide electrical stimulation to constrict blood vessels and regulate blood flow to liver, gallbladder, duodenum and pancreas; placed in superior mesenteric artery 908 to provide electrical stimulation to constrict Vascular and regulate blood flow to the first two thirds of the pancreas, small intestine, appendix and large intestine; placed in the inferior mesenteric artery 910 to provide electrical stimulation to constrict blood vessels and regulate blood flow to the last third of the large intestine; placed in the inferior phrenic artery 912 to provide electrical stimulation to constrict blood vessels and regulate blood flow to the diaphragm and lower portion of the esophagus; placed in the adrenal artery 914 to provide electrical stimulation to constrict blood vessels and regulate blood flow to the adrenal glands; placed in the renal artery 916 to provide electrical stimulation placed in the gonadal artery 918 to provide electrical stimulation to constrict blood vessels and regulate blood flow to the testicles or ovaries; and in the lumbar artery 920 to provide electrical stimulation to constrict blood vessels and regulate blood flow Flow to the vertebrae, spinal cord, abdominal wall, and lumbar region.

Figure 9B shows the venous site of electrode application corresponding to the organ being operated on. Blood is directed from the stomach, duodenum, gallbladder, and liver and pancreatic head via the portal vein, superior mesenteric vein or their branches; from the jejunum and ileum and appendix via the superior mesenteric vein or its branches; via the superior mesenteric vein, inferior mesenteric vein or Its branches lead from the colon; from the spleen through the splenic vein or its branches; and from the genitourinary system through the renal vein, the internal iliac vein of the gonadal vein or its branches. Thus, electrodes can be placed in the hepatic vein 930 to provide electrical stimulation to constrict blood vessels and regulate blood flow from the liver; in the gonadal vein 932 to provide electrical stimulation to constrict blood vessels and regulate blood flow from the gonads; in the lumbar vein 934 to provide electrical stimulation to constrict blood vessels and regulate blood flow from the spinal cord and body wall; placed in the phrenic vein 936 to provide electrical stimulation to constrict blood vessels and regulate blood flow from the diaphragm; placed in the adrenal glands in vein 938 to provide electrical stimulation to constrict blood vessels and regulate blood flow from the adrenal glands; in renal vein 940 to provide electrical stimulation to constrict blood vessels and regulate blood flow from the kidneys; and in the right 942 or left 944 iliac Intravenous to provide electrical stimulation that constricts blood vessels and regulates blood flow from the pelvic muscles, skin, pelvic viscera, perineum, and buttock area.

In one embodiment, a skin electrode is used to provide the desired stimulation to the blood vessel. FIG. 10A shows an exemplary skin electrode. The helical skin electrode 1000 wraps around the blood vessel and adjusts its diameter to the size of the blood vessel due to its self-crimping properties. In some embodiments, the helical card skin electrode 1000 is made of two layers of silicone, plastic or The substrate sheet layers 1002 and 1004 are composed. A metal strip 1006, such as a platinum foil strip, is placed between the layers 1002, 1004 to provide electrical contact with the blood vessel (not shown). Ribbon 1006 is soldered to wire 1008, eg, Teflon insulated stranded stainless steel wire, for electrical connection. In some embodiments, the window 1010 is about 1 mm wide and is cut within the barrel above the platinum band 1006 to make electrical contact with the blood vessel.

Figure 10B shows another exemplary card skin electrode design that can be used to provide electrical stimulation in embodiments of the present specification. In some embodiments, the skin electrode 1020 is made of polydimethylsiloxane (PDMS) or polyimide and almost completely surrounds the blood vessel during surgery. The skin card electrode 1020 includes a cylindrical portion 1021 configured to wrap around a blood vessel, the cylindrical portion 1021 having a cut-out 1022 for placing the skin card electrode 1020 around the blood vessel. A plurality of electrodes 1023 are placed in the cylindrical portion 1021 for contact with blood vessels during surgery. In various embodiments, electrical stimulation energy is provided to the skin electrodes 1000, 1020 of Figures 10A and 10B, respectively, via connection to a pulse generator via connecting wires 1008, 1028. In other embodiments, the card skin electrodes 1000, 1020 are wirelessly coupled to the pulse generator using radio frequency (RF) connections, ultrasonic connections, thermal connections, magnetic connections, electromagnetic connections, or optical connections. Figure 1OC shows another exemplary card skin electrode 1030 known in the art for use in providing electrical stimulation in embodiments of the present specification. The skin electrode 1030 surrounds the blood vessel during surgery. The skin-on electrode 1030 includes a cylindrical portion 1031 with an incision 1032 for placing the skin-on electrode 1030 around a blood vessel and electrodes 1033 positioned in pairs along the length of the cylindrical portion 1031. Figure 10D shows yet another exemplary card skin electrode 1040 for use in providing electrical stimulation in embodiments of the present specification. The skin electrode 1040 surrounds the blood vessel during surgery. The skin-on electrode 1040 includes a cylindrical portion 1041 with electrodes 1043 located in short, separate, exposed cylindrical segments distributed longitudinally along the length of the cylindrical portion 1041, the cylindrical portion 1041 having a surface for connecting the skin-on electrode 1040. An incision 1042 is placed around the blood vessel.

In various embodiments, the skin electrodes of the present specification are configured to apply a pressure of less than 100 mm Hg on a blood vessel to bring the electrode into physical contact with the vessel wall without mechanically significantly blocking blood flow.

In another embodiment, clamp electrodes are used to provide the desired stimulation to the blood vessel. Figure 11 shows an exemplary clamp electrode for providing electrical stimulation to a blood vessel. The clamp electrode 1100 includes an upper plate 1102 , a lower plate 1104 , a clipper 1106 , a knob 1108 , a connector 1110 , a nut 1112 and an electro plate 1114 . Additional connectors (not shown) are located on the underside of the lower board 1104 . In one embodiment, the clamp electrode 1100 is used to provide electrical stimulation by being connected to a pulse generator 1116 by means of a connecting wire 1118. In another embodiment, clamp electrode 1100 is wirelessly coupled to pulse generator 1116 using a radio frequency (RF) connection, ultrasonic connection, thermal connection, magnetic connection, electromagnetic connection, or optical connection. The clamp electrode 1100 is spring actuated about a pivot point 1103 coupling the upper plate 1102 and lower plate 1104. The user presses on the rear surfaces of the upper plate 1102 and lower plate 1104 to open the clamp electrode 1100 about the pivot point 1103 . The anterior or distal ends 1102d, 1104d of the upper and lower plates 1102, 1104 are positioned around the vessel and the user removes pressure from the posterior surface, allowing the distal ends 1102d, 1104d to approach the vessel by spring-actuated movement around the pivot point 1103.

Figure 12 shows a laparoscopic forceps 1200 for placing a clamping electrode 1202 on a blood vessel, according to an embodiment of the present specification. In other embodiments, any suitable device for placing clamp electrodes within a blood vessel can be used. Laparoscopic forceps 1200 includes a shaft portion 1204 and a grasper 1202 for applying a medical device, such as a clamp electrode, to a desired location within the body. As is known, forceps similar to laparoscopic forceps 1200 can be inserted into the body through the mouth, nose, or other body orifice, such as, but not limited to, the anus, or can be inserted through a laparoscopic trocar. In other embodiments, laparoscopic forceps 1200 are used to implant expandable electrodes intravascularly.

Figure 13A shows an expandable electrode 1302 with a lead 1306 within a catheter 1304 for placement within a blood vessel. As shown, an expandable electrode 1302 coupled to lead 1306 is inserted into catheter 1304 for placement of electrode 1302 within a blood vessel. Figure 13B shows the electrode 1302 of Figure 13A in an expanded configuration and extending from the catheter 1304 for placement within a blood vessel. Lead 1306 also extends out of catheter 1304 and electrode 1302 has been expanded to contact the vessel wall. Catheter 1304 is similar to catheters known in the art for accessing the vascular system or placing pacemaker leads.

FIG. 14A shows a catheter 1404 having an expandable electrode 1402 positioned within a blood vessel 1408 according to an embodiment of the present specification. As shown, an expandable electrode 1402 coupled to lead 1406 is inserted into catheter 1404 for placement of electrode 1402 within blood vessel 1408. Catheter 1404 is used to pierce blood vessel 1408 to place electrode 1402 therein. In various embodiments, blood vessel 1408 can be any artery or vein in need of bleeding treatment. FIG. 14B shows the electrode 1402 of FIG. 14A extending from the catheter 1404 and expanding within the blood vessel 1408. As shown in Figure 14B, electrode 1402 extends out of distal end 1410 of catheter 1404 and expands. FIG. 14C shows an electrode 1402 positioned within a blood vessel 1408 according to an embodiment of the present specification. Prongs 1402a and 1402b of electrode 1402 expand to contact walls 1408a, 1408b of blood vessel 1408, and catheter 1404 is removed from the body lumen containing blood vessel 1408, leaving lead 1406 to connect electrode 1402 to the pulse generator. FIG. 14D shows electrode 1402 of FIG. 14C connected to implantable pulse generator (IPG) 1411 via lead 1406 . Once electrode 1402 has been positioned such that tips 1402a and 1402b of electrode 1402 contact walls 1408a, 1408b of blood vessel 1408, lead 1404 is connected to the IPG. Thus, electrodes 1402 can be used to provide electrical stimulation of a desired frequency/amplitude to blood vessel 1408 at desired intervals for a desired period of time. In some embodiments, microprocessor 1412 is operably connected to IPG 1411 and controls stimulation parameters generated by the IPG and administered by electrodes 1402.

In one embodiment, electrical stimulation can be used to induce vasoconstriction in a blood vessel (eg, an artery) prior to arterial transplantation. Figure 14E shows electrical stimulation applied to a femoral artery with an obstruction in a human leg. As shown, occlusion 1420 exists in femoral artery 1422 proximal to popliteal artery 1424 in human leg 1426. Electrodes 1428 are placed within the femoral artery 1422 and current of the desired amplitude and frequency is supplied for the desired time interval via an electrical signal generator (ESG) 1430, which is also connected to the application to the proximal femoral artery. Grounding pad 1432 for the skin of 1422 . The ground pad provides a return path for the current applied through electrode 1402, eliminating the need to place a second electrode within the artery. Electrical stimulation applied to the femoral artery 1422 via the electrode 1428 causes vasoconstriction of the femoral artery 1422 and prevents bleeding therefrom when the femoral artery 1422 is cut for application of the skin implant. Figure 14F shows arterial graft 1434 applied after vasoconstriction of femoral artery 1422 in human leg 1426 as described with reference to Figure 14E. Vasoconstriction is achieved by electrical stimulation of the femoral artery 1422 provided by electrodes 1428 connected to the ESG 1430, which also has a ground pad 1432. Once vasoconstriction has occurred, an arterial implant 1434 connecting the femoral artery 1422 and the popliteal artery 1424 is applied to bypass the occlusion 1420 without allowing significant blood loss from the femoral artery 1422. At the end of the procedure, electrical stimulation was discontinued and blood supply under the vascular access was restored.

Figure 14G shows the arterial and venous structure of blood vessels in the human leg. As shown, the human leg includes the femoral artery 1450, the popliteal artery 1452, the anterior tibial artery 1454, the posterior tibial artery 1456, the peroneal artery 1458, the dorsal foot artery 1460, and the arch 1462. The human leg also contains external iliac vein 1464, femoral vein 1466, perforating vein 1468, great saphenous vein 1470, lesser saphenous vein 1472, anterior tibial vein 1474, posterior tibial vein 1476, and dorsal venous arch 1478. As described with reference to Figures 14A-14F, electrical stimulation may be applied by placing electrodes near (or within) any of the arteries and veins shown in Figure 14G to induce vasoconstriction and prevent blood loss from vascular structures.

In another embodiment, electrical stimulation can be applied by placing electrodes near (or within) any of the arteries and veins shown in Figure 14G to induce vasodilation and increase blood flow in these vascular structures to Treat low blood flow conditions such as peripheral vascular disease. FIG. 14H shows a catheter 1401 having an expandable electrode 1403 covering an expandable balloon 1405 located within a blood vessel 1407 according to an embodiment of the present specification. As shown, an expandable electrode 1403 coupled to lead 1409 is inserted through catheter 1401 with balloon 1405 such that when balloon 1405 is in a deflated state (as shown in Figure 14H ), electrode 1403 is not expanded to allow the electrode to be removed 1403 and balloon 1405 are placed within vessel 1407. The catheter 1401 is used to puncture the blood vessel 1407 to place the electrodes 1403 and balloon 1405 within the blood vessel 1407. In various embodiments, blood vessel 1407 can be any artery or vein in need of bleeding treatment.

FIG. 14I shows the electrode 1403 of FIG. 14H extending from the catheter 1401 and inflated due to the expansion/inflation of the balloon 1405 within the blood vessel 1407. As shown in Figure 14I, the balloon 1405 is extended out of the distal end 1413 of the catheter 1401 and expanded/inflated, causing the electrode 1403 to also expand around the balloon 1405. Figure 14J shows an electrode 1403 placed within a blood vessel 1407 in a dilated state and covering a dilation balloon 1405, according to an embodiment of the present specification. The expanded balloon 1405 places electrodes 1403 covering the balloon 1405 in contact with the wall of the blood vessel 1407 to deliver electrical stimulation. Once balloon 1405 and electrodes 1403 are expanded within vessel 1407 , catheter 1401 is removed from the body lumen containing vessel 1407 , leaving lead 1409 to connect electrode 1403 to implantable pulse generator (IPG) 1415 . As can be seen in Figures 14I and 14J, the expansion of the balloon 1405 within the blood vessel 1407 restricts the flow of blood therein, providing a mechanical means of preventing bleeding in the blood vessel 1407. Also, the extension electrodes 1403 are used to provide electrical stimulation of the desired frequency/amplitude to the blood vessel 1407 at desired time intervals for the desired time period, thereby further impeding blood flow.

Abnormal uterine bleeding (formerly known as dysfunctional uterine bleeding or DUB) is irregular uterine bleeding that occurs in the absence of identifiable pelvic pathology, general medical illness, or pregnancy. It reflects a disruption of the normal circulatory pattern of ovulation hormone stimulation of the endometrial lining. Bleeding is unpredictable in many ways. It may be too heavy or too light, and it may be prolonged, frequent, or random.

The blood supply to the uterus originates primarily from the uterine artery. These arteries originate from the hypogastric artery and swing toward the uterus where they divide into descending and ascending branches. The descending branch runs down the side wall of the cervix and vagina. The ascending branch passes up the parauterine and continues below the fallopian tubes. Frequent anterior and posterior branches enter the vagina, cervix, and uterus. In one embodiment, the present specification provides a method of treating uterine bleeding by applying electrical stimulation near the hypogastric artery, uterine artery, or a branch of the uterine artery or to the nerves supplying the hypogastric or uterine artery to prevent uterine bleeding conduct. In various embodiments, continuous or intermittent stimulation can be applied. In one embodiment, the stimulus applied is controlled by an algorithm that predicts the onset of menstrual bleeding and is applied before or during menstrual bleeding to prevent uterine bleeding. Figure 15A shows the application of electrical stimulation to the uterine artery 1504 to prevent uterine bleeding. As shown, electrodes 1502 are applied to the uterine artery 1504, which connects to the internal ileac artery 1506 and supplies blood to the uterus 1508. Electrodes 1502 are connected to pulse generator 1510 by means of connecting leads 1512 to provide electrical stimulation to cause uterine artery contractions 1504. In some embodiments, the patient uses her menstrual cycle map to trigger stimulation. In other embodiments, a software application or external device running on a mobile device such as a smartphone predicts the onset of the patient's menstrual cycle and triggers the onset of stimulation. In other embodiments, either the patient's premenstrual symptoms or the first occurrence of bleeding can be used to trigger stimulation. Since most DUBs occur around the time of a patient's normal menstrual bleeding, such timed stimulation would eliminate the need for stimulation during non-"at-risk" periods.

In another embodiment, uterine bleeding is controlled by applying electrical stimulation to the uterine wall. Figure 15B shows the application of electrical stimulation to the uterine wall 1536 to prevent uterine bleeding. Electrodes 1520 are inserted into the uterus 1526 via the vagina 1530, the external orifice 1528 of the cervical os, the cervix 1534, and the internal orifice 1532 of the cervical os, coupled to a lead 1522, which in turn is coupled to a pulse generator 1524 to provide electrical stimulation. Within the uterus 1526, the electrodes 1520 are expanded into contact with the uterine wall 1536 to provide electrical stimulation to the wall 1536 to control uterine bleeding. The same electrodes can then be used at a later time to provide thermal therapy to the uterine cavity without removing the electrodes.

In one embodiment, an inflatable balloon catheter with surface electrodes as known in the art is inserted into the uterine cavity and then inflated so that the electrodes are in contact with the uterine wall. Electrical stimulation of the uterine wall is applied via surface electrodes to stop uterine bleeding. Figure 15C shows the use of balloon catheter 1540 to apply electrical stimulation to uterine cavity wall 1546 to prevent uterine bleeding. As shown, a balloon catheter 1540 with a plurality of surface electrodes 1542 is placed in the uterine cavity 1544, and the balloon 1540 is inflated so that the electrodes 1542 are in contact with the uterine wall 1546. In one embodiment, a non-thermal current is applied to the electrode 1542 to cause vasoconstriction without coagulation resulting in hemostasis or reduced blood flow. Additional coagulation current may be applied through the same electrodes 1542 to further aid in hemostasis. In some embodiments, the balloon is inflated to a pressure where, in addition to electrical vasoconstriction and hemostasis, it causes occlusion of uterine bleeding. The same electrodes can then be used at a later time to provide thermal therapy to the uterine cavity without removing the electrodes.

Figure 15D shows an expandable balloon catheter 1550 having an expandable electrode 1552 for controlling bleeding according to embodiments of the present specification. Balloon 1550 contains bipolar electrodes 1552 that expand when balloon 1550 is expanded to contact the body surface. Balloon 1550 is shown in an unexpanded state in Figure 15D. Once inserted into the body lumen by any suitable device (eg, via an endoscope), the balloon 1550 is inflated to fill the lumen, thereby bringing the electrodes 1552 into physical contact with the body lumen wall, eg, as shown in Figure 15C. In various embodiments, the balloon is made of latex, silicone, flexible polyvinyl chloride (PVC), PTFE, ePTFE, polyester (PET), polyethylene terephthalate, cross-linked polyethylene, nylon or PET or Other material compositions known in the art. in various embodiments. The electrodes are composed of gold, platinum, iridium, titanium, stainless steel, cobalt-based alloys, or combinations thereof, or any other electrode material known in the art. In various embodiments, the volume of the balloon is between 1 cc and 500 cc.

In one embodiment, the present specification provides a method of treating a tumor by modulating blood flow to the tumor. A condition called ischemia-reperfusion results in damage to normal organs, especially those with high metabolic rates. It is reasonable to assume that ischemia-reperfusion can also lead to damage to cancerous cells with very high metabolic rates. However, it is difficult to generate reversible ischemia followed by reperfusion using standard embolization, which is often irreversible. Therefore, it is desirable to reversibly control blood flow to the tumor, thereby causing ischemia, followed by reperfusion to produce tumor cell damage and cell death. Also, the higher metabolic rate of cancerous cells compared to surrounding normal tissue may allow selective damage to cancerous cells with less damage to surrounding non-cancerous cells supplied by the same blood vessels. Intermittent mechanical clamping has been shown to protect tumors from accelerated tumor growth. Intermittent mechanical clamping also results in protection against liver damage caused by ischemia or reperfusion. However, the process of intermittent mechanical clamping is cumbersome and time consuming during surgery. Reversible electrically mediated clamping of blood vessels can be achieved by electrical stimulation of vascular structures through reliable and reversible control of blood flow to the organ. In one embodiment, the present specification provides a method of regulating blood flow to an organ during tumor surgery by applying electrical stimulation to the blood vessels of the organ to induce changes in vascular tone. In one embodiment, the present specification also provides a method of modulating blood flow to the liver during hepatobiliary surgery by applying electrical stimulation to the hepatic artery to induce changes in hepatic artery tone.

Blood flow can be modulated or altered by supplying electrical stimulation to the blood vessels supplying the tumor or to the nerves that innervate the blood vessels supplying the tumor. In the case of cancerous cells, the blood supply can be altered for various durations, which then allow normal blood flow, leading to tumor reperfusion and damage to the cancerous cells. The durations are selected by defining the duration of ischemia or altered blood flow required to cause cancerous cell damage and the duration of ischemia or altered blood flow required to cause noncancerous cell damage, and stimulating blood vessels to reach Duration within two defined durations to selectively destroy cancerous cells. Figure 16 shows the treatment of tumors in the liver by applying electrical stimulation according to embodiments of the present specification. The tumor 1602 in the liver 1604 can be treated by applying electrical stimulation to the hepatic artery 1606, which supplies blood to the liver 1604. Electrodes 1608 are connected to pulse generator 1610 via connecting leads 1612 to provide electrical stimulation. In various embodiments, the electrodes are placed inside the hepatic artery in electrical contact with the intima or on the hepatic artery in electrical contact with the adventitia or one of the branches of the hepatic artery or the nerve supplying the hepatic artery. In various embodiments, the electrodes are placed using standard laparoscopic, radiological, endoscopic, or stereotaxic techniques. In various embodiments, the electrical stimulation therapy is combined with any one or a combination of chemotherapy, radiation therapy, arterial embolization, chemoembolization, or radio-embolization. The concomitant use of electrical stimulation with embolization can help vary the size of the embolic particles required for improved efficacy.

The liver is divided into segments for the purpose of research and to provide medical treatment. Figure 17A shows a segment of a human liver. Liver 1700 includes right anterior superior and inferior portions 1708s, 1708i and corresponding right posterior superior and inferior portions 1702s, 1702i located between right hepatic vein 1704 and intermediate hepatic vein 1706. In addition, the liver 1700 is segmented into left upper and lower parts 1710s, 1710i, a middle part 1712 and a caudate process 1713. The liver can also be treated by defining various parts or lobes. Figure 17B shows a lobe of a human liver. Liver 1700 includes left 1714 and right 1716 lobes, square lobe 1718 near gallbladder 1720, and caudate lobe 1722 near inferior vena cava 1724.

In one embodiment, bleeding in a liver segment can be controlled by applying electrical stimulation to one or more vessels supplying blood to the segment, thereby stopping bleeding. Figure 17C shows control of hepatic hemorrhage by applying electrical stimulation according to embodiments of the present specification. As shown in Figure 17C, a pair of electrodes 1730 are placed proximate to blood vessels 1732 supplying blood to segments 1702s, 1702i, 1708s, and 1708i. Electrodes 1730 are placed proximate the hemorrhagic segment and the blood vessels 1732 supplying them, and are coupled to a pulse generator 1736 via leads 1734 to apply electrical stimulation to the blood vessels 1734 to control hemorrhage in the liver segment.

In another embodiment, the presence in liver segments can also be controlled by placing one or more electrodes on the surface or in the parenchyma of one or more segments of the liver and applying electricity to blood vessels in the liver parenchyma Stimulate to stop bleeding. Figure 17D shows control of hepatic hemorrhage by applying electrical stimulation according to another embodiment of the present specification. As shown in FIG. 17D , a pair of electrodes 1740 are placed on the surface or in the parenchyma of the actively bleeding liver segment 1708s to apply electrical stimulation to generate an electric field, which in turn is stimulated by wires 1742 connected to a pulse generator 1744 Blood vessels within liver segment 1708s to control bleeding.

Figure 18A shows the anchor 1802 used to hold the lead 1804 within the vessel. In various embodiments, an electrode coupled to a lead is inserted into a blood vessel to place the electrode within the blood vessel, eg, as shown in Figures 14A-14D. A blood vessel can be any artery or vein that needs bleeding treatment. Figure 18A shows anchors 1802 used to hold the lead 1804 of the electrode 1806 in a desired location within the vessel and close to the vessel wall, thereby preventing clot formation on the lead wall. Lead 1804 terminates in connector 1807 for connection to a pulse generator (not shown), enabling electrical stimulation of the blood vessel.

In various embodiments, the electrode 1806 coupled to the lead 1804 is inserted into the intravascular catheter to place the electrode 1806 within the blood vessel. A catheter is used to pierce the blood vessel to place the electrodes 1806 therein. In one embodiment, the anchor 1802 also includes a patch 1808 for sealing the puncture site at the point where the catheter enters the blood vessel to prevent bleeding or hematoma formation. In various embodiments, the patch is composed of PTFE, silicone, or other materials known in the art for creating intravascular stent implants. In various embodiments, the patch size ranges from 2 to 200 times the diameter of the intravascular catheter, which in turn determines the size of the puncture opening.

Figure 18B shows another embodiment of an anchor 1850 for retaining lead 1824 within a blood vessel. Anchors 1850 are used to hold the lead 1824 of the electrode 1826 in the desired location within the vessel. In various embodiments, the anchors 1850 are partially or fully covered with PTFE 1851 or similar material for intravascular implants and function in positioning the wire body and sealing the puncture site. Lead 1824 terminates in connector 1827 for connection to a pulse generator (not shown), enabling electrical stimulation of the blood vessel.

In one embodiment, articulating jaws are used to provide electrical stimulation to the blood vessel in order to control bleeding from the blood vessel. An electrical stimulation device with articulating jaws can be passed through the patient's body via an endoscope and can be placed proximate to a vascular structure to apply electrical stimulation to the vascular structure. 19A shows a surgical device 1902 having articulating jaws 1904 that can operate as a forceps, similar to hot biopsy forcep operation, from an opening 1906 in the tip 1908 of an endoscope 1910 Prominent, close to blood vessel 1912 with hemorrhage. The surgical device 1902 that provides electrical stimulation may be monopolar or bipolar, and in one embodiment, includes an impedance sensor that measures impedance to control the delivery of electrical stimulation to the blood vessel 1912.

Figure 19B shows electrical stimulation applied to a blood vessel via articulating jaws 1904 in accordance with embodiments of the present specification. Electrical stimulation causes vasoconstriction of blood vessel 1912 without coagulation. In one embodiment, additional coagulation current may also be applied to the vessel 1912 after vasoconstriction to seal the vascular structure. In various embodiments, the coagulation current has a frequency of >100 kHz, and is preferably in the range of 300 kHz to 3 MHz. As shown in Figure 19B, articulating jaws 1904 are used to grasp the vascular structure prior to application of electrical stimulation to induce mechanical tamponade, thereby assisting in vasoconstriction.

In various embodiments, one or more active or passive wireless microdevices are permanently implanted adjacent to the vascular structures supplying the patient's limb. In the case of traumatic injury to a limb, the device is activated with an external device, such as a hand-held remote control device, to deliver electrical stimulation to control bleeding from vascular structures, as explained earlier in this specification. In various embodiments, the implantable microdevice comprises an inert passive device or an active microstimulator as known in the art. Figure 20A shows a site within a human body for implantation of an active or passive wireless microdevice according to embodiments of the present specification. As shown, microdevices 2002 and 2004 were implanted near (or within) the right subclavian vein 2006, and microdevice 2008 was implanted near (or within) the left subclavian vein 2010. Similarly, microdevice 2012 is implanted near (or within) right femoral vein 2014 extending from right external iliac vein 2016 and microdevice 2018 is implanted near left external iliac vein 2020 (or within it) implanted. As will be apparent to those skilled in the art, the implantation locations of the microdevices shown in FIG. 20A are exemplary only, and the microdevices used to provide electrical stimulation may be implanted in various other blood vessels in the human body. Figure 20B shows an exemplary implantable microdevice 2019 for delivering electrical stimulation to a blood vessel, according to embodiments of the present specification. Microdevice 2019 can be implanted using needle 2021.

20C shows an exemplary handheld remote control device 2022 for activating an implanted microdevice to deliver electrical stimulation to a blood vessel, according to embodiments of the present specification. The hand-held remote control can be operated by the patient or another person receiving electrical stimulation. Figure 20D shows another exemplary handheld remote control device 2024 for activating an implanted microdevice to deliver electrical stimulation to a blood vessel, according to another embodiment of the present specification. In one embodiment, the remote control device 2024 may be a smartphone with a predefined application for activating an implanted micro-device running on it. As shown in Figure 20D, in some embodiments, the screen of the remote control 2024 displays a list of various implanted microdevices located in different areas of the body, and based on the site of the injury, specific microdevices can be activated via the remote control 2024 to Electrical stimulation is delivered to defined body areas.

Figure 20E shows an exemplary implantable microdevice 2030 for delivering electrical stimulation to a blood vessel in accordance with embodiments of the present specification. Microdevice 2030 includes a communication antenna 2032 for communicating with a handheld remote control device, such as those shown in Figures 20C and 20D, to activate microdevice 2030. The communication antenna 2032 is coupled to a battery 2034 or any mechanism for storing energy, such as a capacitor used to power the microdevice 2030. The electronic circuitry of the microdevice 2030 includes a magnetic sensor 2036 coupled to a charging coil 2038, which in turn is coupled to one or more biopotential and temperature sensors 2040, all located on an ASCI chip 2042, which is 2042 is coupled to analog capacitors 2044 and analog electrodes and communication antennas 2046. Figure 20F shows an exemplary circuit diagram 2050 of a microdevice for delivering electrical stimulation to a blood vessel in accordance with embodiments of the present specification.

Figure 20G shows another exemplary implantable microdevice 2060 for delivering electrical stimulation to a blood vessel in accordance with embodiments of the present specification. Microdevice 2060 includes an elongated silicon substrate 2062 that includes stimulation electrodes 2064 and reference electrodes 2066 placed proximally and distally, respectively. The portion of substrate 2062 between the proximal and distal ends includes electronic circuits such as tank capacitors 2068, power conditioning circuits 2070 coupled to recirculating coil antenna 2072, and output stage 2074 and control electronics 2076, It is coupled with a hybrid charge storage chip capacitor 2078 as shown. The entire substrate 2062 containing all electrodes 2064, 2066 and all electronic circuits is packaged in a glass capsule 2080 or any other hermetically sealed package.

Figure 21 is a flowchart showing steps for regulating blood flow by applying electrical stimulation to a blood vessel according to an embodiment of the present specification. At step 2102, at least one electrode is placed near an artery, vein, nerve or organ wall supplying the artery or vein. In various embodiments, any of the electrodes described with reference to Figures 6 and 10A-14D may be used. At step 2104, the electrodes are connected to an electrical pulse generator to provide electrical pulses of a desired frequency and amplitude for a desired duration. In one embodiment, the first electrical stimulation response threshold for vasoconstriction is predetermined. In addition, a second response threshold for thrombosis in the subject is predetermined. In one embodiment, the amplitude of the electrical pulse is below the predetermined response threshold for thrombus formation, but above the response threshold for vasoconstriction, such that stimulation produces an advantage of vasoconstriction over thrombus formation.

At step 2106, the electrodes are activated to provide electrical stimulation for regulating blood flow to organs supplied by arteries or veins. In one embodiment, the electrodes are activated and electrical stimulation is controlled via an algorithm running on a computing device coupled to an electrical pulse generator. In one embodiment, the algorithm may stimulate electrodes only when there is bleeding in the corresponding artery, vein or organ. In another embodiment, an algorithm may induce electrodes to apply a first stimulus that causes arterial/venous constriction such that greater than 50% or 75% or 90% of maximum blood flow is maintained and a second stimulus in the event of bleeding. % of baseline blood flow, the second stimulation reduces blood flow to less than 50%, 25% or 10% of maximum blood flow. In other embodiments, the electrical stimulation is applied for a duration wherein the change in blood flow is maintained for at least 1 minute after the electrical stimulation ceases. In other embodiments, the electrical stimulation is applied for another duration, wherein the change in blood flow is maintained for at least 5 minutes after the electrical stimulation ceases. In other embodiments, electrical stimulation is turned on and off intermittently to maintain adequate control of blood flow, thereby allowing adequate hemostasis without compromising the viability of organs supplied by blood vessels. The duty cycle in such cases ranges from 1% to 99%. In some embodiments, the ideal duty cycle range is 10%-90%. In other embodiments, stimulation parameters including specific duty cycles are configured to produce vasodilation.

In one embodiment, the present specification provides a method of treating bleeding by applying electrical stimulation at a predefined location, wherein the bleeding site is downstream of the stimulation location. Electrical stimulation can be provided by placing electrodes (connected to an electrical pulse generator) near (or within) the blood vessel to regulate blood flow downstream of the bleeding site.

In various embodiments, currents with frequencies up to 1000 KHz can be used to stimulate blood vessels without causing thermal damage to the vessel wall or coagulation. Electrical stimulation above 1000KHz usually produces some kind of heat that can damage blood vessels. In one embodiment, electrical stimulation can be applied to blood vessels supplying a body organ, causing vasoconstriction to prevent hemorrhagic conditions in the body organ during a surgical procedure. In embodiments, less than 25% vasoconstriction is non-therapeutic, while between 25% and 50% vasoconstriction is used to prevent hemorrhagic conditions. Also, use greater than 50% vasoconstriction to treat bleeding.

In various embodiments, each stimulation site serves a different bleeding site downstream of the stimulation site. In an exemplary embodiment, a stimulation site in a patient's upper extremity is used to regulate blood flow (thus treating a bleeding condition) throughout the limb downstream of the upper extremity stimulation site. Similarly, stimulation sites in a patient's lower extremities are used to regulate blood flow (thus treating bleeding conditions) throughout the limb downstream of the lower extremity stimulation sites.

Figure 22A illustrates providing stimulation to a blood vessel in a patient's upper extremity to control bleeding downstream of the stimulation site, in accordance with embodiments of the present specification. As mentioned earlier, nerves supplying blood vessels can also be stimuli to achieve the same desired therapeutic effect. As shown, the upper limb or arm 2200 contains blood vessels such as the subclavian artery 2202, axillary artery 2204, deep brachial artery 2206, brachial artery 2208, radial artery 2210, ulnar artery 2212, deep palmar arch 2214, and superficial palmar arch 2216. In the case of a hemorrhage in one of the blood vessels in the arm 2200, such as the exemplary hemorrhage in the brachial artery 2208 shown in FIG. 22A, electrical stimulation is applied to the blood vessel at a location upstream of the hemorrhage 2218. In an exemplary embodiment, stimulation is applied to the axillary artery 2204 by placing an electrode 2220 coupled to an implantable pulse generator 2222 via a lead 2221 in or near the axillary artery 2204. Electrodes 2220 activated via pulse generator 2222 provide electrical stimulation to constrict axillary artery 2204 and regulate blood flow downstream into hemorrhage 2218 in brachial artery 2208. In embodiments, electrodes 2220 may be placed proximate any living blood vessel at a location upstream of bleeding site 2218. In one embodiment, a palpable vascular region at a distance in the range of 0.5 to 5 cm from the blood vessel is identified for electrode 2220 placement, wherein the electrode placement site is at least 1 cm from the bleeding site 2218.

Figure 22B illustrates providing stimulation to a blood vessel in a patient's upper extremity to control bleeding downstream of the stimulation site, according to another embodiment of the present specification. As shown, the upper extremity or arm 2230 contains blood vessels, such as the subclavian vein 2232, axillary vein 2234, cephalic vein 2236, brachial vein 2238, radial vein 2240, ulnar vein 2242, deep palmar arch 2244, superficial palmar arch 2246, epicardial vein 2248, median cubital vein 2250, and median forearm vein 2252. In the case of a hemorrhage in one of the blood vessels of the arm 2230, such as the exemplary hemorrhage 2258 in the vitreous vein 2248 shown in FIG. 22B, electrical stimulation is applied to the blood vessel at a location upstream of the hemorrhage 2258. In an exemplary embodiment, stimulation is applied to the axillary vein 2234 by placing an electrode 2260 coupled to an implantable pulse generator 2262 via a lead 2261 in or near the axillary vein 2234. Electrodes 2260 activated by pulse generator 2262 provide electrical stimulation to constrict the axillary vein 2234 and regulate blood flow downstream to hemorrhage 2258 in the basal vein 2248. In embodiments, electrode 2260 may be placed proximate any living blood vessel at a location upstream of bleeding site 2258. In one embodiment, a palpable vascular region at a distance ranging between 0.5 and 5 cm from the skin surface is identified for placement of the electrode 2260, wherein the electrode placement site is at least 1 cm from the bleeding site 2258.

Figure 23 shows overstimulation of blood vessels in a patient's lower extremities to control bleeding downstream of the stimulation site, in accordance with embodiments of the present specification. As shown, lower extremity or leg 2300 contains blood vessels, including both arteries and veins, such as femoral artery 2302, popliteal artery 2304, anterior tibial artery 2306, posterior tibial artery 2307, peroneal artery 2308, dorsal pedis artery 2310, and arch 2312 , external iliac vein 2314, femoral vein 2316, perforating vein 2318, great saphenous vein 2320, small saphenous vein 2322, anterior tibial vein 2324, posterior tibial vein 2326 and dorsal venous arch 2328. In the case of a hemorrhage in one of the blood vessels in the leg 2300, such as the exemplary hemorrhage 2330 in the popliteal artery 2304 shown in FIG.

In an exemplary embodiment, stimulation is applied to the femoral artery 2302 by placing an electrode 2332 coupled to an implantable pulse generator 2334 via a lead 2333 in or near the femoral artery 2302. Electrodes 2332 activated via pulse generator 2334 provide electrical stimulation to constrict femoral artery 2302 and regulate blood flow downstream to hemorrhage 2330 in popliteal artery 2302. In embodiments, electrodes 2332 can be placed in electrical communication with any living blood vessel at a site upstream of bleeding site 2330. In one embodiment, a palpable vascular area at a distance ranging between 0.5 and 5 cm from the skin surface is identified for placement of electrodes 2332, wherein the electrode placement site is at least 1 cm from the bleeding site 2330.

In the case of a hemorrhage in one of the veins in the leg 2300, such as the exemplary hemorrhage 2336 in the saphenous vein 2320 shown in FIG.

In an exemplary embodiment, stimulation is applied to the external iliac vein 2314 by placing an electrode 2342 coupled to an implantable pulse generator 2340 via lead 2341 in or near the external iliac vein 2314. Electrodes 2342 activated via pulse generator 2340 provide electrical stimulation to constrict external iliac vein 2314 and regulate blood flow downstream into hemorrhage 2336 in saphenous vein 2320. In embodiments, electrodes 2342 can be placed in electrical communication with any living blood vessel at a site upstream of bleeding site 2336. In one embodiment, a palpable vascular area at a distance ranging between 0.5 and 5 cm from the skin surface is identified for placement of the electrode 2342, wherein the electrode placement site is at least 1 cm from the bleeding site 2336.

The embodiments described with reference to Figures 22A, 22B, and 23 are effective in treating bleeding that occurs after trauma to the upper and lower extremities, respectively, such as by accident.

Figure 24 shows stimulation of blood vessels in a patient's abdomen to control bleeding downstream of the stimulation site, according to embodiments of the present specification. As shown, via blood vessels such as phrenic artery 2402, celiac artery 2404, hepatic artery 2406, right gastric artery 2408, adrenal artery 2410, renal artery 2411, gonadal artery 2412, lumbar artery 2414, middle sacral artery 2416, abdominal aorta 2418, The splenic artery 2420, left gastric artery 2422, superior mesenteric artery 2424, inferior mesenteric artery 2426, and common iliac artery 2428 supply blood to the abdomen 2400. In the case of a hemorrhage in one of the vessels in the abdomen 2400, such as the exemplary hemorrhage 2430 in the lumbar artery 2414 shown in FIG. 24, electrical stimulation is applied to the vessel at a site upstream of the hemorrhage 2430. In an exemplary embodiment, stimulation is applied to the superior mesenteric artery 2424 by placing an electrode 2432 coupled to an implantable pulse generator via lead 2433 in or near the superior mesenteric artery 2424. Electrodes 2432 activated by pulse generator 2434 provide electrical stimulation to constrict the superior mesenteric artery 2424 and regulate blood flow downstream into the lumbar artery 2414 for hemorrhage 2430 . In embodiments, electrodes 2432 are placed proximate any living blood vessels at a location upstream of bleeding site 2430. In one embodiment, a palpable vascular region at a distance ranging between 0.5 and 5 cm from the skin surface is identified for placement of electrodes 2342, wherein the electrode placement site is at least 1 cm from the bleeding site 2430.

Since bleeding is commonly observed in the abdominal region as a result of surgical procedures, in embodiments, electrodes used to provide electrical stimulation are placed at one or more predetermined locations within the patient's abdominal cavity prior to the surgical procedure. During a surgical procedure, blood loss from a blood vessel can be controlled by activating electrodes placed near any blood vessel upstream of the bleeding to provide electrical stimulation, as explained with reference to FIG. 24 . Thus, in embodiments, vasoconstriction by applying electrical stimulation to the blood vessel for controlling blood loss functions as a real-time electronic tourniquet, and is used to prevent bleeding conditions during surgery. Such an approach is preferred over using physical fixtures in real time because it is faster and can be adjusted more easily.

Figure 25 is a flowchart showing steps for controlling bleeding in a patient's upper or lower extremity by applying electrical stimulation to blood vessels upstream of the bleeding site, according to embodiments of the present specification. At step 2502, stimulation therapy is assessed for a patient with bleeding in a blood vessel of an upper or lower extremity. At step 2504, at least one electrode is placed on the surface of the vessel proximate the upstream of the bleeding vessel and supplying the bleeding vessel. In various embodiments, the electrodes are placed at least 1 cm upstream of the bleeding site. In various embodiments, the blood vessel is an artery or a vein including at least one of the subclavian artery, axillary artery, deep brachial artery, brachial artery, radial artery, ulnar artery, deep palmar arch, and superficial palmar arch, whereby The veins include at least one of the subclavian vein, the axillary vein, the cephalic vein, the brachial vein, the radial vein, the ulnar vein, the deep palmar arch, the superficial palmar arch, the precious vein, the median cubital vein, and the median forearm vein. In other embodiments, the blood vessel is an artery or a vein, the artery including at least one of the femoral artery, the popliteal artery, the anterior tibial artery, the posterior tibial artery, the peroneal artery, the dorsal foot artery, and the plantar arch, the vein including the iliac artery At least one of the external vein, the femoral vein, the perforating vein, the great saphenous vein, the small saphenous vein, the anterior tibial vein, the posterior tibial vein, and the dorsal venous arch. At step 2506, the electrodes are connected to an electrical pulse generator. At step 2508, the pulse generator generates electrical stimulation applied to the upstream supply vessel to constrict the vessel and control bleeding in the bleeding vessel. The electrical stimulation has a pulse duration, pulse amplitude and pulse frequency selected such that the electrical stimulation is effective to induce vasoconstriction in the artery or the vein.

26A is a flowchart showing steps for preventing and/or controlling bleeding in a patient during abdominal surgery by applying electrical stimulation to blood vessels upstream of a potential bleeding site, according to embodiments of the present specification. At step 2602, surgery is initiated in the patient's abdominal region. At step 2604, at least one electrode is placed proximate to the blood vessel upstream of and supplying the blood vessel involved in the abdominal procedure. At step 2606, the electrodes are connected to an electrical pulse generator. Bleeding during the surgical procedure is identified at step 2608. At step 2610, the pulse generator generates electrical stimulation applied to the upstream supply vessel to constrict the vessel and control bleeding in the downstream vessel during surgery to prevent and/or control bleeding, wherein the electrical stimulation has a pulse duration, pulse amplitude and pulse frequency , and wherein the pulse duration, pulse amplitude, and pulse frequency are selected such that the electrical stimulation is effective to induce vasoconstriction.

Figure 26B is a flowchart showing steps for preventing prospective bleeding in a patient during abdominal surgery by applying electrical stimulation to blood vessels upstream of a potential bleeding site, according to embodiments of the present specification. At step 2620, a procedure is initiated in the patient's abdominal region, where initiation of the procedure is defined as exposing an area near the blood vessels involved in the procedure. At step 2622, prior to the formation of a bleed, at least one electrode of the stimulation device is placed in the abdominal region at a location upstream of a blood vessel and in electrical communication with blood vessels supplying the blood vessel. At step 2624, the at least one electrode is connected to an electrical pulse generator. The procedure then continues at step 2626. Before initiating a surgical technique in which an increased likelihood of bleeding is anticipated, at step 2628, the pulse generator generates electrical stimulation that is applied to the upstream vessel for a predetermined period of time, wherein the electrical stimulation has a pulse duration, a pulse amplitude, and a pulse frequency, and wherein The pulse duration, the pulse amplitude, and the pulse frequency are selected such that the electrical stimulation is effective to induce vasoconstriction of upstream vessels and reduce blood flow, thereby preventing or controlling bleeding in the involved vessels in the abdominal region. The surgical technique then continues at step 2630.

In various embodiments, the predetermined period of time during which electrical stimulation is administered prior to the surgical technique is equal to at least 30 seconds. In some embodiments, electrical stimulation is administered for at least 10 seconds during the surgical technique. In some embodiments, electrical stimulation is administered prior to beginning the surgical technique and for the duration of the remainder of the procedure. Furthermore, in some embodiments, such as in some high-risk situations, the at least one electrode is configured to remain in the abdominal region of the patient for a period ranging from 1 to 7 days and to administer electrical stimulation postoperatively for treatment Postoperative bleeding.

Figure 27 is a flow chart showing the steps of positioning a stimulation site on the skin surface and providing electrical stimulation to control bleeding in accordance with embodiments of the present specification. At step 2702, the physician identifies a palpable vascular area that is 0.5 to 5 cm from the patient's skin surface and at least 1 cm from the bleeding site. At step 2704, at least one electrode is placed proximate the palpable vessel region. At step 2706, the electrodes are connected to an electrical pulse generator. At step 2708, the pulse generator generates electrical stimulation applied to the palpable vascular region to constrict the blood vessel and control bleeding.

In other embodiments, it may be desirable to increase blood flow in blood vessels to treat conditions or diseases associated with decreased blood flow, such as peripheral vascular disease, Raynaud's disease, coronary artery disease, cerebrovascular disease, and the like. In various embodiments, this is accomplished by modifying the duty cycle of the stimulation algorithm so that electrical stimulation is delivered to the vessel at >25% duty cycle, and therapy is delivered >25% of the days.

The above examples merely illustrate the many applications of the system of this specification. Although only a few embodiments of the present invention have been described herein, it should be understood that the present invention may be embodied in many other specific forms without departing from the spirit or scope of the invention. Accordingly, the present examples and embodiments are considered to be illustrative and not restrictive, and the invention may be modified within the scope of the appended claims.

Unless otherwise specified, all headings are for the convenience of the reader and should not be used to limit the meaning of the text following the heading.

Claims (20)

1. A method of preventing anticipated bleeding in an artery or vein of a patient's upper extremity using at least one electrode in electrical communication with a pulse generator, the method comprising: disposing the at least one electrode near the surface of the patient's arteries or veins, wherein the arteries are the subclavian, axillary, deep brachial, brachial, radial, ulnar, deep and superficial palmar arches At least one of or the veins is at least one of the subclavian vein, axillary vein, cephalic vein, brachial vein, radial vein, ulnar vein, deep palmar arch, superficial palmar arch, epiphysis, median cubital vein, and median forearm vein one, and wherein said location is at least 1 cm upstream of said location of expected bleeding; and causing the pulse generator to generate electrical stimulation applied to the artery or the vein through at least one electrode, wherein the electrical stimulation has a pulse duration, a pulse amplitude, and a pulse frequency, and wherein the pulse duration, the pulse duration, and the pulse frequency are selected. The pulse amplitude and the pulse frequency are such that the electrical stimulation is effective to induce vasoconstriction in the artery or vein, thereby preventing the expected bleeding. 2. The method of claim 1, wherein the pulse duration is in the range of 1 μsec to 500 msec, the pulse amplitude is in the range of 1 V to 250 V, and the pulse frequency is in the range of 1 Hz to 100 kHz. 3. The method of claim 1, wherein the at least one electrode is at least one of a cuff electrode and a clamp electrode, and wherein disposing the at least one electrode comprises attaching the cuff electrode Or the clamp electrode is placed in direct physical contact with the location. 4. The method of claim 1, wherein a radio frequency (RF) receiver is coupled to the at least one electrode, and an RF transmitter is coupled to the pulse generator and in wireless communication with the RF receiver, and wherein The method also includes causing the pulse generator to generate electrical stimulation to be administered by the at least one electrode and wirelessly transmitting the electrical stimulation from the RF transmitter to the RF receiver. 5. The method of claim 1, further comprising using a microprocessor operably connected to the pulse generator to selectively set the pulse duration, the pulse amplitude, and the pulse frequency. 6. A method of preventing anticipated bleeding in an artery or vein of a lower extremity of a patient using at least one electrode in electrical communication with a pulse generator, the method comprising: Disposing the at least one electrode at a location proximate to the surface of an artery or vein of the patient, wherein the artery is the femoral artery, the popliteal artery, the anterior tibial artery, the posterior tibial artery, the peroneal artery, the dorsal pedis artery, and the middle of the foot At least one of the or said veins is at least one of the external iliac vein, femoral vein, perforating vein, great saphenous vein, lesser saphenous vein, anterior tibial vein, posterior tibial vein and dorsal venous arch, and wherein said location is in all at least 1 cm upstream of the location of the expected bleeding; and causing the pulse generator to generate electrical stimulation applied to the artery or the vein through at least one electrode, wherein the electrical stimulation has a pulse duration, a pulse amplitude, and a pulse frequency, and wherein the pulse duration, the pulse duration, and the pulse frequency are selected. The pulse amplitude and the pulse frequency are such that the electrical stimulation is effective to induce vasoconstriction in the artery or vein, thereby preventing the expected bleeding. 7. The method of claim 6, wherein the pulse duration ranges from 1 μsec to 500 msec, the pulse amplitude ranges from 1 V to 250 V, and the pulse frequency ranges from 1 Hz to 100 kHz. 8. The method of claim 6, wherein the at least one electrode is a skin electrode or a clamp electrode, and disposing the at least one electrode comprises placing the skin electrode or the clamp electrode directly with the location physical contact. 9. The method of claim 6, wherein a radio frequency (RF) receiver is coupled to the at least one electrode, and an RF transmitter is coupled to the pulse generator and in wireless communication with the RF receiver, and The method also includes causing the pulse generator to generate electrical stimulation to be administered by the at least one electrode and wirelessly transmitting the electrical stimulation from the RF transmitter to the RF receiver. 10. The method of claim 6, further comprising using a microprocessor operably connected to the pulse generator to selectively set the pulse duration, the pulse amplitude and the pulse frequency. 11. A method of controlling bleeding in a patient prior to a planned surgical procedure, the method comprising: initiating surgery in the patient's abdominal region; arranging at least one electrode of the stimulation device at a location upstream of a blood vessel in the abdominal region and in electrical communication with a blood vessel supplying the blood vessel prior to the formation of the hemorrhage; connecting the at least one electrode to an electrical pulse generator; identify bleeding during the surgical procedure; and causing the pulse generator to generate electrical stimulation applied to an upstream vessel, wherein the electrical stimulation has a pulse duration, a pulse amplitude and a pulse frequency, and wherein the pulse duration, the pulse amplitude and the pulse frequency are selected, The electrical stimulation is made effective to cause vasoconstriction of the upstream vessels and reduce blood flow to control bleeding of the vessels in the abdominal region. 12. The method of claim 11, wherein the pulse duration is in the range of 1 μsec to 500 msec, the pulse amplitude is in the range of 1 V to 250 V, and the pulse frequency is in the range of 1 Hz to 100 kHz. 13. The method of claim 11, wherein the at least one electrode is a skin electrode or a clamp electrode, and disposing the at least one electrode comprises placing the skin electrode or the clamp electrode directly with the location physical contact. 14. The method of claim 11, wherein a radio frequency (RF) receiver is coupled to the at least one electrode, and an RF transmitter is coupled to the pulse generator and in wireless communication with the RF receiver, the The method also includes causing the pulse generator to generate electrical stimulation to be administered by the at least one electrode and wirelessly transmitting the electrical stimulation from the RF transmitter to the RF receiver. 15. The method of claim 11, further comprising selectively setting the pulse duration, the pulse amplitude and the pulse frequency using a microprocessor operably connected to the pulse generator. 16. A method of preventing bleeding in a patient prior to a planned surgical procedure, the method comprising: commencing surgery in the patient's abdominal region, wherein commencing surgery is defined as exposing an area proximate to blood vessels in the abdominal region involved in the surgery; arranging at least one electrode of the stimulation device at a location upstream of a blood vessel in the abdominal region and in electrical communication with a blood vessel supplying the blood vessel prior to the formation of the hemorrhage; connecting the at least one electrode to an electrical pulse generator; proceed with said operation; causing the pulse generator to generate electrical stimulation applied to an upstream vessel for a predetermined period of time, wherein the electrical stimulation has a pulse duration, a pulse amplitude, and a pulse frequency, prior to initiating a surgical technique that anticipates an increased likelihood of bleeding, and wherein said pulse duration, said pulse amplitude and said pulse frequency are selected such that said electrical stimulation is effective to cause vasoconstriction of said upstream blood vessels and reduce blood flow to prevent bleeding of blood vessels in said abdominal region; and Continue with the described surgical technique. 17. The method of claim 16, wherein the predetermined period of time is equal to at least 30 seconds. 18. The method of claim 16, wherein the electrical stimulation is administered for at least 10 seconds during the surgical procedure technique. 19. The method of claim 16, wherein the electrical stimulation is administered prior to initiating the surgical technique and during the remainder of the procedure. 20. The method of claim 16, wherein the at least one electrode is configured to remain in the abdominal region for a period ranging from 1 to 7 days, and wherein the electrical stimulation is administered postoperatively to treat postoperative bleeding.