SU1301414A1 - Method of determining individual sensitivity to cardiotrop preparation - Google Patents

Abstract

To speed up the determination of individual sensitivity to a cardiotropic drug and reduce the risk of complications while testing several drugs (P), a papillary muscle fragment of a pathologically modified mitral valve is isolated from patients with acquired heart defects during surgery for its prosthesis, stripes are cut out of the muscle stretched in chambers, perfused with saline. Myocardial strips are stimulated with an electrostimulator with rectangular pulses of 5 ms duration. For each P, a threshold value of the stimulus is selected, at which the induced contractile responses occur. Upon reaching the stationary amplitude of the induced contractile responses, further stimulation is carried out by pulses 1.2-1.5 times higher than the threshold value. Then, the test Ps are added to the perfusate and, by increasing the amplitude of the contractions and the time to attaining the maximum amplitude increase, individual sensitivity to P. 6 tab. a 4 4

Description

The invention relates to medicine, namely cardiology, and can be used to select drug therapy, taking into account the individual sensitivity of the heart muscle of patients to drugs.

The purpose of the invention is to accelerate and reduce the risk of complications while simultaneously testing several drugs by conducting testing on the cardiac muscle of a patient outside his body.

The method of drying is as follows.

A fragment of the papillary muscle of the pathologically modified mitral valve of patients with acquired heart defects during surgery, regarding its prosthesis, was isolated. Strips are cut out of the muscle, stretched in the chambers, perfused with saline. For each drug, a threshold is selected for rectangular electrical stimuli at which contractions occur. After the stationary amplitude of the induced contractile responses is reached, further stimulation of the drying is effected by pulses 1.2–1.5 times higher than the threshold value, then test drugs are added to the perfusate and the changes in the amplitude of contractions caused by different preparations are compared. drugs of different strengths, choose the most adequate to the patient in the postoperative period.

ten

After receiving full abbreviations (myocardium stripes were refined for 100 minutes for the excitatory responses, and further studies continued to be stimulated. At the same time, with stimulus amplitudes, the jj threshold in Table 1 was determined and corrected the magnitude of the stimuli, set it at 20% above the threshold. After the pre-After completion of the preparation of the strips

the contraction of the stationary amplitude of the sokra-myocardium, and to the experiment on the first of them

Example 1. Patient B., 45 years old. Final clinical diagnosis: rheumatic mitral disease, aortic insufficiency, calcification of the mitral valve of the IV degree, atrial fibrillation, circulatory disorder of the II B degree. Patient's complaints of shortness of breath, pain in the heart area, palpitations were noted. An aortic and mitral valve replacement was performed with an artificial blood circulation apparatus. In the course of the operation, acute heart failure and cardiac arrhythmia were noted.

From the mitral valve removed

papillary muscle was quickly isolated, then three strips with a diameter of up to 1 mm and a length of 2-3 mm were cut out of it. Myocardial fragments were placed in Plexiglas bioblocks, in which a channel of Tyrode standard solution was maintained (pH 7.5; T 28 ° WITH). The preparations were fixed with ligatures to electromechanical sensors and stretched by about 30% of the initial length. Next, the myocardial stripes were stimulated by an electric field using an electrically stimulated torus with rectangular pulses of 5 ms duration. At the same time, for each drug, the threshold value of the stimulus was selected, at which the induced contractile responses occurred. Fragment activity

patient's myocardium and threshold stimulus values for example 1 are presented in table. one.

Table 1

Drop in amplitude of contractions

Stationary

amplitude

abbreviations

Digoxin was fed at a concentration of 4-10 g / ml, and the second was treated with 4X XloV / ml. The maximum increase in the amplitude of the strip No. 1 under the influence of digoxin 71% was achieved 130 minutes after the start

Digoxin Korglikon

2236 2305

To check the correctness of the prediction obtained on the papillary muscle strips before surgery in patient B., the change in the minute volume of the heart under the influence of digoxin and corglycon was investigated. The drugs were administered with an interval of 48 hours. MiDigoxin 0.5

7.7

Korglion 0.2

6.5

Example 2. Patient K-, 31 years old. Zaklyu-55 serd, mitral valve calcification IV

strong clinical diagnosis: rheumatism, atrial fibrillation. During the posterior mitral stenosis of the IV degree, the thromus-the last time, the state of sharp deterioration of the left atrium and the right ear was set: shortness of breath, palpitations appeared.

la effect of substance. Similar values for strip No. 2 under the action of Korglikon, respectively, 114% and 120 min. The absolute values of the increments of the amplitude of contractions are given in Table. 2

table 2

71

114

130 120

The volume was recorded using tetrapolar rheography. In the patient, the increase in the minute volume under the influence of Korglikon, as in the testing on the bands, was higher than with the same dose of digoxin (Table 3).

Table 3

Within method error

120

thirty

thirty

general weakness, enlarged liver. An operation was performed: thrombectomy from the left, auricles and an auricle of the right auricle, prosthetics of the mitral valve with an artificial blood circulation apparatus. During the operation, the valve is excised completely, the disc prosthesis “EMIX MSh-29.

The papillary muscle was quickly removed from the removed mitral valve, then three strips with a diameter of 4 mm and a length of 4-5 mm were cut out of it, myocardial fragments were placed in Plexiglas bioblocks, in which the flow of the solution was maintained

21

thirty

sixteen

After receiving complete contractile responses, the myocardial strips continued to be stimulated. At the same time, every 5-10 min. The excitation threshold was determined and the value of stimuli was corrected, setting it at 10% above the threshold. After reaching the steady-state amplitude of contractions (100 min), the excitation threshold was established and further studies were continued with the amplitudes of the stimuli listed in Table. four.

After completing the preparation of myocardial strips for the experiment on the first one

Digoxin Korglikon

1738 4323

Tyrode standard composition (pH 7.5, temperature 28 ° C). The preparations were fixed with ligatures to electromechanical sensors and stretched by about 30% of the initial length. Next, the myocardial stripes were stimulated by an electric field using an electrostimulator with rectangular pulses of 5 ms duration. At the same time, for each drug, a threshold value of the stimulus was selected at which contractile responses occurred. The contractile activity of the patient's myocardial fragment and the values of the threshold stimuli for example 2 are presented in Table. four.

Table 4

Stationary

amplitude

abbreviations

Drop in amplitude of contractions

Digoxin was applied at a concentration, and the second was treated with 4X X10L / ml.

The maximum increase in the amplitude of the strip No. 1 under the influence of digoxin was 237% and was reached 160 minutes after the onset of action of the substance. Similar values for strip No. 2 under the action of Korglikon, respectively, 136% and 140 min. The absolute values of the amplitude increments of the indicated reductions are given in Table. five.

T a

faces

237,136

160,140

To check the correctness of the prediction obtained on the papillary muscle strips before the operation in patient K-, the change in the minute volume of the heart under the influence of digoxin and corglycone was investigated. The drugs were administered at intervals of 48 hours. The minute volume was recorded using tetrapolar rheography. Patient K. has an increase in the minute volume of the heart under influence of digoxin 0.53

Korglion 0.25

80

The use of the proposed method for the individualization of cardiotropic drugs allows, based on a comparison of the magnitude of the inotropic effect of different drugs of unidirectional action, to make a prediction on the ratio of their effectiveness to the contractile function of the patient's heart in the postoperative period.

In contrast to the known method, 10–20 drugs can be subjected to simultaneous testing, because, due to their small size (diameter 0.1–1 mm, length 2–5 mm), the number of strips that can be cut from the papillary muscle fragment is not limiting. Thus, the proposed method significantly improves the productivity of research aimed at individualizing therapy, and makes it possible to test for the effectiveness of the previously inaccessible number of drugs.

The proposed method completely eliminates the risk of any complications, since the removal of papillary muscle fragments is dictated by the course of the operation, and the drug itself is tested outside the patient's body.

The use of digoxin was higher than with the introduction of the same dose of corglycon, which fully coincides with the estimate obtained in experiments on fragments of the papillary muscle of this patient.

A comparison of the change in the patient's minute volume of the patient under the influence of digoxin and corglycone is given in Table. 6

Table 6

136 60

120 60

The present invention can also be successfully used to predict life threatening patient's inhibition of the pumping function of the heart under the influence of the side effects of certain drugs (for example, a number of antiarrhythmics).

Claims (1)

Invention Formula The method of determining individual sensitivity to a cardiotropic drug by studying the effect of the drug on the heart muscle, characterized in that, in order to accelerate and reduce the risk of complications while simultaneously testing several drugs, during the operations on mitral valve replacement in patients with acquired heart defects, a fragment is isolated papillary muscles of the mitral valve, strip out of it, stretch them in the chambers, perfuse with saline, pick up the threshold rectangular electrical stimuli, at which contractions occur, reach a stationary amplitude due to contractile responses, further stimulation is carried out by pulses of contractions and time to reach 1.2–1.5 times the threshold value; for maximizing the amplitude of the optome, the test card is added to the perfusate to determine the individual sensitivity diotropic drugs and to increase the amp-k drug.