Igor Efimov
Washington University in St. Louis, Biomedical Engineering, Faculty Member
Cardiomyopathy is associated with cardiac Na+ channel downregulation that may contribute to arrhythmias. Previously, we have shown that elevated intracellular NADH causes a decrease in cardiac Na+ current (INa) signaled by an increase in... more
Cardiomyopathy is associated with cardiac Na+ channel downregulation that may contribute to arrhythmias. Previously, we have shown that elevated intracellular NADH causes a decrease in cardiac Na+ current (INa) signaled by an increase in mitochondrial reactive oxygen species (ROS). In this study, we tested whether the NADH–mitochondria ROS pathway was involved in the reduction of INa in a nonischemic cardiomyopathic model and correlated the findings with myopathic human hearts.
Journal of Molecular and Cellular Cardiology, Volume 33, Issue 6, Pages A85, June 2001, Authors:Vladimir Nikolski; Aleksandre Sambelashvill; Igor Efimov.
Abstract Optical mapping has become an increasingly important tool to study cardiac electrophysiology in the past 20 years. Multiple methods are used to process and analyze cardiac optical mapping data, and no consensus currently exists... more
Abstract Optical mapping has become an increasingly important tool to study cardiac electrophysiology in the past 20 years. Multiple methods are used to process and analyze cardiac optical mapping data, and no consensus currently exists regarding the optimum methods. The specific methods chosen to process optical mapping data are important because inappropriate data processing can affect the content of the data and thus alter the conclusions of the studies.
Abstract The development of human cardiovascular systems physiology is inhibited by the lack of multiscale functional physiological data, which represents human heart physiology at the molecular, cellular, tissue, organ, and system... more
Abstract The development of human cardiovascular systems physiology is inhibited by the lack of multiscale functional physiological data, which represents human heart physiology at the molecular, cellular, tissue, organ, and system levels. We have developed an experimental approach to study explanted human hearts in vitro at multiple physiological scales with a wide array of imaging modalities.
Abstract Stability of a vortex was studied in a modified cellular automation model. The model includes dependence of wave velocity of excitation interval and front curvature. Two kinds of vortex instability are observed, as found also in... more
Abstract Stability of a vortex was studied in a modified cellular automation model. The model includes dependence of wave velocity of excitation interval and front curvature. Two kinds of vortex instability are observed, as found also in models based on partial differential equations: meandering of the vortex and vortex drift in a heterogeneous medium.
Abstract: Using Optical Coherence Tomography (OCT), an emerging imaging modality, we have produced both 3D and 4D images of cardiac architecture. We captured 3D images of rabbit Purkinje fiber networks and we also created a 4D... more
Abstract: Using Optical Coherence Tomography (OCT), an emerging imaging modality, we have produced both 3D and 4D images of cardiac architecture. We captured 3D images of rabbit Purkinje fiber networks and we also created a 4D representation of a beating stage 28 chicken embryo heart. For the 4D reconstruction, we generated a movie by employing a gated reconstruction technique.
Abstract The response of cardiac cells to the external electrical field is a crucial factor contributing to the success and failure of defibrillation. We aimed to determine a possible contribution of electroporation to optically recorded... more
Abstract The response of cardiac cells to the external electrical field is a crucial factor contributing to the success and failure of defibrillation. We aimed to determine a possible contribution of electroporation to optically recorded response during high-intensity shocks. We applied 10 ms anodal and cathodal stimuli of different intensities to the rabbit heart epicardium during plateau phase of the action potential with 6-mm-diameter electrode.
Abstract Recently published optical mapping studies of larger mammals, including humans, have identified functionally discrete sinoatrial exit pathways of activation. This is in line with earlier mapping studies of the dog and the human... more
Abstract Recently published optical mapping studies of larger mammals, including humans, have identified functionally discrete sinoatrial exit pathways of activation. This is in line with earlier mapping studies of the dog and the human but in contrast with findings in the mouse and the rabbit, wherein a propagation wave front pattern of activation has been described.
Abstract There is a need for accurate measurements of mechanical strain and motion of the heart both in vitro and in vivo. We have developed a new structured-light imaging system capable of epicardial shape measurement at 333 fps at a... more
Abstract There is a need for accurate measurements of mechanical strain and motion of the heart both in vitro and in vivo. We have developed a new structured-light imaging system capable of epicardial shape measurement at 333 fps at a resolution of 768× 768 pixels. Here we present proof-of-concept data from our system applied to a beating rabbit heart in vitro to measure epicardial mechanics.
Summary Technological advances often precede scientific breakthroughs that have led to leaps in our understanding of human physiology. The advent of the electrical galvanometer Was a landmark advancement that enabled careful study of the... more
Summary Technological advances often precede scientific breakthroughs that have led to leaps in our understanding of human physiology. The advent of the electrical galvanometer Was a landmark advancement that enabled careful study of the electrical activation of the heart.
Optical imaging of voltage and calcium in the heart, which we pioneered 2 decades ago, 1–3 is indeed an important and increasingly more valuable technique in the investigation of arrhythmia mechanisms, and we concur that significant... more
Optical imaging of voltage and calcium in the heart, which we pioneered 2 decades ago, 1–3 is indeed an important and increasingly more valuable technique in the investigation of arrhythmia mechanisms, and we concur that significant advances in the field justify a review of recent progress. In their recent review of the topic, Herron et al tackle a presentation of the essential components that are necessary to build state-of-the-arts optical mapping instruments.
We thank Drs Selvaraj and Nair for the opportunity to discuss the clinical relevance of our recent findings in explanted human hearts and to bridge the gap between clinical and basic electrophysiology research methodologies. Using the... more
We thank Drs Selvaraj and Nair for the opportunity to discuss the clinical relevance of our recent findings in explanted human hearts and to bridge the gap between clinical and basic electrophysiology research methodologies. Using the basic science methodology of optical mapping, which is not yet available in clinical electrophysiological laboratories, we have recently found that end-stage heart failure results in anatomically heterogeneous repolarization remodeling in humans.
It has recently been suggested that patients with severe heart failure and wide QRS benefit from cardiac resynchronization therapy. 1− 4 The suggested mechanism is an improved and shorter activation of the ventricles resulting in temporal... more
It has recently been suggested that patients with severe heart failure and wide QRS benefit from cardiac resynchronization therapy. 1− 4 The suggested mechanism is an improved and shorter activation of the ventricles resulting in temporal resynchronization of the left ventricular (LV) walls. However, whether the LV alone or both ventricles need to be paced simultaneously to obtain this effect remains controversial.
A method for extinguishing a cardiac arrhythmia utilizes destructive interference of the passing of the reentry wave tip of an anatomical reentry through a depolarized region created by a relatively low voltage electric field in such a... more
A method for extinguishing a cardiac arrhythmia utilizes destructive interference of the passing of the reentry wave tip of an anatomical reentry through a depolarized region created by a relatively low voltage electric field in such a way as to effectively unpin the anatomical reentry. Preferably, the relatively low voltage electric field is defined by at least one unpinning shock (s) that are lower than an expected lower limit of vulnerability as established, for example, by a defibrillation threshold test.
Biventricular Shocking Leads: Introduction: A single lead active can configuration has been widely used in patients with life-threatening ventricular arrhythmias. Occasionally, however, such a defibrillation lead configuration may not... more
Biventricular Shocking Leads: Introduction: A single lead active can configuration has been widely used in patients with life-threatening ventricular arrhythmias. Occasionally, however, such a defibrillation lead configuration may not achieve adequate defibrillation thre.shold (DFT). The purpose of this stndy was to determine whether addition of a left ventricular (LV) lead can improve defihrillation efficacy.
Abstract A highly parallel autowave method for pattern analysis and topological feature detection is presented. It is invariant against translations, rotations and scaling of the input pattern. The method yields an increase in... more
Abstract A highly parallel autowave method for pattern analysis and topological feature detection is presented. It is invariant against translations, rotations and scaling of the input pattern. The method yields an increase in computational speed of 3 to 6 orders of magnitude in comparison with a sequential (von Neumann) computer. The method can be realized in principle using only one chip with simple uniform connections of elements.
Heart Rhythm, Volume 2, Issue 5, Pages S257, May 2005, Authors:Blanca Rodriguez, PhD; Li Li, MS; James C. Eason, PhD; Igor R. Efimov, PhD; Natalia A. Trayanova, PhD.
Conclusion: In experiments and simulations, the helical rotation of epicardial excitation isochrones caused by pacing at increasing depth in the myocardium correlated with the helical three-dimensional architecture of ventricular fibers.... more
Conclusion: In experiments and simulations, the helical rotation of epicardial excitation isochrones caused by pacing at increasing depth in the myocardium correlated with the helical three-dimensional architecture of ventricular fibers. In contrast, repolarization was independent of the activation sequence and was mainly guided by spatial differences in APDs between apex and base.
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Conclusion: Our data provide the first experimental support of the hypothesis implicating virtual electrode-induced phase singularity in defibrillation failure in the Langendorff-perfused rabbit heart. Optimal biphasic shock has a higher... more
Conclusion: Our data provide the first experimental support of the hypothesis implicating virtual electrode-induced phase singularity in defibrillation failure in the Langendorff-perfused rabbit heart. Optimal biphasic shock has a higher defibrillation efficacy because it does not produce virtual electrode-induced phase singularities.
Fluorescent Imaging of AV N. Introduction: We .sought to determine the precise pathways of engagement of the AV node during sinus rhythm. Methods and Results: Langendorff-perfused rabbit hearts were stained with 20 /xM of the... more
Fluorescent Imaging of AV N. Introduction: We .sought to determine the precise pathways of engagement of the AV node during sinus rhythm. Methods and Results: Langendorff-perfused rabbit hearts were stained with 20 /xM of the voltage-sensitive dye di-4-ANEPPS. Preparations containing the right atrium, sinoatrial (SA) and AV nodes, and interatrial septum were subsequently dissected and mapped in vitro using a 16 X 16 photodiode array with an adjustable resolution of 150 to 750 fim per diode.
It has been recently speculated that CEW pulses might cause a direct injury to cardiac or nerve cells [1, 2]. This injury is referred to as electroporation and is the subject of this chapter in which we will explore this phenomenon and... more
It has been recently speculated that CEW pulses might cause a direct injury to cardiac or nerve cells [1, 2]. This injury is referred to as electroporation and is the subject of this chapter in which we will explore this phenomenon and investigate the possibility of it occurring with CEW pulses.
Voltage-sensitive dyes and imaging techniques have proved to be indispensable tools for use in in vitro electrophysiological studies. To avoid motion artifacts in optical recordings, electromechanical uncouplers such as 2, 3-butanedione... more
Voltage-sensitive dyes and imaging techniques have proved to be indispensable tools for use in in vitro electrophysiological studies. To avoid motion artifacts in optical recordings, electromechanical uncouplers such as 2, 3-butanedione monoxime (BDM) are required. In this study, we sought to determine whether the voltage-sensitive dye RH421 had an effect on the contractility of heart muscle, either alone or in the presence of BDM.
Abstract Vagal stimulation results in complex changes of pacemaker excitability in the sinoatrial node (SAN). To investigate the vagal effects in the rabbit SAN, we used optical mapping, which is the only technology that allows resolving... more
Abstract Vagal stimulation results in complex changes of pacemaker excitability in the sinoatrial node (SAN). To investigate the vagal effects in the rabbit SAN, we used optical mapping, which is the only technology that allows resolving simultaneous changes in the activation pattern and action potentials morphologies. With the use of immunolabeling, we identified the SAN as a neurofilament 160-positive but connexin 43-negative region (n= 5).
Controlling cardiac chaos is often achieved by applying a large damaging electric shock-defibrillation. It removes all waves, without differentiating reentries and normal waves, anatomical and functional reentries. Anatomical reentries... more
Controlling cardiac chaos is often achieved by applying a large damaging electric shock-defibrillation. It removes all waves, without differentiating reentries and normal waves, anatomical and functional reentries. Anatomical reentries can be removed by anti-tachycardia pacing (ATP) as well. But ATP requires the knowledge of the position of the reentry, and an access to it with an invasive stimulating electrode.
Journal of Molecular and Cellular Cardiology, Volume 41, Issue 6, Pages 949-951, December 2006, Authors:Igor R. Efimov.
Page 1. 998 Reversal of Repolarization Gradient Does Not Reverse the Chirality of Shock-Induced Reentry in the Rabbit Heart YUANNA CHENG, MD. VLADIMIR NIKOLSKl. PH.D., and IGOR R. EFIMOV. PH.D. From the Department of Cardiology. Cleveland... more
Page 1. 998 Reversal of Repolarization Gradient Does Not Reverse the Chirality of Shock-Induced Reentry in the Rabbit Heart YUANNA CHENG, MD. VLADIMIR NIKOLSKl. PH.D., and IGOR R. EFIMOV. PH.D. From the Department of Cardiology. Cleveland Clinic Foundation. Cleveland. Ohio Chirality and Repolarization.
Cardiac experimental electrophysiology is in need of a well-defined Minimum Information Standard for recording, annotating, and reporting experimental data. As a step towards establishing this, we present a draft standard, called Minimum... more
Cardiac experimental electrophysiology is in need of a well-defined Minimum Information Standard for recording, annotating, and reporting experimental data. As a step towards establishing this, we present a draft standard, called Minimum Information about a Cardiac Electrophysiology Experiment (MICEE).
Virtual electrode induced phase singularity hypothesis explains the origin of cardiac arrhythmias caused by artificial electrical induction of rotors, ie vortex-like self-sustained sources of activity. This mechanism is thought to... more
Virtual electrode induced phase singularity hypothesis explains the origin of cardiac arrhythmias caused by artificial electrical induction of rotors, ie vortex-like self-sustained sources of activity. This mechanism is thought to underlie both stimulus-induced arrhythmias and shock defibrillation therapy. In this paper, we extend this hypothesis to three dimensions using the bidomain model of cardiac tissue.
Pacing and defibrillation have become the leading therapeutic treatments of heart rhythm disorders, including bradycardia and tachycardia. The success of these therapies is largely due to centuries of scientific inquiry into the... more
Pacing and defibrillation have become the leading therapeutic treatments of heart rhythm disorders, including bradycardia and tachycardia. The success of these therapies is largely due to centuries of scientific inquiry into the fundamental mechanisms of bioelectric phenomena in the heart. History of successful development of bioelectric therapies includes development of experimental and theoretical methodologies, novel bioengineering approaches, and state-of-the-art clinical implantable device therapies.
Abstract The aim of this study is to examine how structural discontinuity and functional remodeling changes the susceptibility to alternans of action potential duration (APD) in a rabbit model of chronic myocardial infarction (MI).... more
Abstract The aim of this study is to examine how structural discontinuity and functional remodeling changes the susceptibility to alternans of action potential duration (APD) in a rabbit model of chronic myocardial infarction (MI). Optical mapping experiments using voltage-sensitive dyes were performed in 14 rabbit hearts.
Abstract Defibrillation efficacy is decreased in infarcted hearts, but the mechanisms by which infarcted hearts are more vulnerable to electric shocks than healthy hearts remain poorly understood. The goal of this study was to provide... more
Abstract Defibrillation efficacy is decreased in infarcted hearts, but the mechanisms by which infarcted hearts are more vulnerable to electric shocks than healthy hearts remain poorly understood. The goal of this study was to provide insight into the 3D mechanisms for the increased vulnerability to electric shocks in infarcted hearts. We hypothesized that changes in virtual electrode polarizations (VEPs) and propagation delay through the peri-infarct zone (PZ) were responsible.
Conclusion: Lidocaine increased MS ULV due to slowing of shock-induced break-excitation wavefronts, which resulted in enhanced probability of survival of virtual electrode induced phase singularity. Lidocaine had no effect on BS ULV... more
Conclusion: Lidocaine increased MS ULV due to slowing of shock-induced break-excitation wavefronts, which resulted in enhanced probability of survival of virtual electrode induced phase singularity. Lidocaine had no effect on BS ULV because no break excitation was induced by BS. Reduction of conduction velocity by lidocaine resulted in increased dispersion of repolarization and led to upper limit of VP increase for both MS and BS.(J Cardiovasc Electrophysiol, Vol. 14, pp. S237-S248, October 2003, Suppl.)
Implantable cardioverter defibrillator studies have established the superiority of biphasic waveforms over monophasic waveforms. However, external defibrillator studies of biphasic waveforms are not as widespread. Our objective was to... more
Implantable cardioverter defibrillator studies have established the superiority of biphasic waveforms over monophasic waveforms. However, external defibrillator studies of biphasic waveforms are not as widespread. Our objective was to compare the defibrillation efficacy of clinically used biphasic waveforms, ie, truncated exponential, rectilinear, and quasi-sinusoidal (Gurvich) waveforms in a fibrillating heart model.
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The atrioventricular conduction axis, located in the septal component of the atrioventricular junctions, is arguably the most complex structure in the heart. It fulfils a multitude of functions, including the introduction of a delay... more
The atrioventricular conduction axis, located in the septal component of the atrioventricular junctions, is arguably the most complex structure in the heart. It fulfils a multitude of functions, including the introduction of a delay between atrial and ventricular systole and backup pacemaking. Like any other multifunctional tissue, complexity is a key feature of this specialised tissue in the heart, and this complexity is both anatomical and electrophysiological, with the two being inextricably linked.