Effect of electroporation on cardiac electrophysiology.

Defibrillation shocks are commonly used to terminate life-threatening arrhythmias. According to the excitation theory of defibrillation, such shocks are aimed at depolarizing the membranes of most cardiac cells, resulting in resynchronization of electrical activity in the heart. If shock-induced transmembrane potentials are large enough, they can cause transient tissue damage due to electroporation.

Computer three-dimensional reconstruction of the atrioventricular node.

Because of its complexity, the atrioventricular node (AVN), remains 1 of the least understood regions of the heart. The aim of the study was to construct a detailed anatomic model of the AVN and relate it to AVN function. The electric activity of a rabbit AVN preparation was imaged using voltage-dependent dye.

Autonomic control and innervation of the atrioventricular junctional pacemaker.

Background: The main physiologic function of the AV junction is control of timing between atrial and ventricular excitation. However, under pathologic conditions, the AV junction may become the pacemaker of the heart. Unlike the well-characterized sinoatrial node (SAN), autonomic control of the AV junctional pacemaker has not been studied.

Three-dimensional panoramic imaging of cardiac arrhythmias in rabbit heart.

Cardiac fluorescent optical imaging provides the unique opportunity to investigate the dynamics of propagating electrical waves during ventricular arrhythmias and the termination of arrhythmias by strong electric shocks. Panoramic imaging systems using charge-coupled device (CCD) cameras as the photodetector have been developed to overcome the inability to monitor electrical activity from the entire cardiac surface. Photodiode arrays (PDAs) are known to have higher temporal resolution and signal quality, but lower spatial resolution compared to CCD cameras.

Atrioventricular conduction with and without AV nodal delay: two pathways to the bundle of His in the rabbit heart.

The electrophysiological properties of atrioventricular (AV) nodal dual pathways have traditionally been investigated with premature stimuli delivered with right atrial pacing. However, little is known about the functional characteristics of AV nodal inputs outside of this context. Superfused rabbit triangle of Koch preparations (n = 8) and Langendorff-perfused hearts (n = 10) were paced throughout the triangle of Koch and mapped electrically and optically for activation pattern, electrogram and optical action potential morphologies, stimulation thresholds, and stimulus-His (S-H) intervals.

Direct measurements of membrane time constant during defibrillation strength shocks.

Background: Defibrillation shocks impose significant energy demand on implantable cardioverter-defibrillators (ICDs). Several modeling studies have been devoted to optimizing shock parameters, and a large number of these studies treat the heart as a simplified lumped network. The time constant of membrane polarization (tau(m)) is a key variable for such modeling efforts.

Gene printer: laser-scanning targeted transfection of cultured cardiac neonatal rat cells.

Heterogeneous gene expression in cardiac cells and tissues which requires targeted delivery of foreign DNA into selected cells or regions is needed for the development of novel therapies. Several techniques have been employed for targeted transfection, such as direct microinjection into cells or targeted electroporation. However, these techniques have limited bandwidth or spatial resolution of transfection.

Mechanisms of unpinning and termination of ventricular tachycardia.

High-energy defibrillation shock is the only therapy for ventricular tachyarrhythmias. However, because of adverse side effects, lowering defibrillation energy is desirable. We investigated mechanisms of unpinning, destabilization, and termination of ventricular tachycardia (VT) by low-energy shocks in isolated rabbit right ventricular preparations (n = 22).

Fluorescence imaging for real-time monitoring of high-intensity focused ultrasound cardiac ablation.

Side effects and limitations of radio-frequency ablation of cardiac arrhythmias prompted search for alternative energy sources and means of their application. High-intensity focused ultrasound (HIFU) is becoming an increasingly attractive modality for ablation because of its unique ability for non-invasive or minimally invasive, non-contact focal ablation in 3D volume without affecting intervening and surrounding cells. The purpose of this study is to develop a real-time monitoring technique to elucidate HIFU-induced modifications of electrical conduction in cardiac tissues and to investigate the HIFU cardiac ablation process to help to achieve optimal HIFU ablation outcome.

Optical mapping of the atrioventricular junction.

In the normal heart, the atrioventricular node (AVN) is part of the sole pathway between the atria and ventricles, and is responsible for the appropriate atrial-ventricular delay. Under normal physiological conditions, the AVN controls appropriate frequency-dependent delay of contractions. The AVN also plays an important role in pathology: it protects ventricles during atrial tachyarrhythmia, and during sinoatrial node failure the atrioventricular (AV) junction assumes the role of pacemaker.

Hibernator Citellus undulatus maintains safe cardiac conduction and is protected against tachyarrhythmias during extreme hypothermia: possible role of Cx43 and Cx45 up-regulation.

Background: Most mammals experience cardiac arrest during hypothermia. In contrast, hibernators remain in sinus rhythm even at body temperatures of 0 degrees C.

Objectives: The purpose of this study was to quantify electrical activity and connexin expression in the heart of hibernating Siberian ground squirrel Citellus undulatus.

Electroporation of the heart.

Defibrillation shocks are commonly used to terminate life-threatening arrhythmias. According to the excitation theory of defibrillation, such shocks are aimed at depolarizing the membranes of most cardiac cells resulting in resynchronization of electrical activity in the heart. If shock-induced changes in transmembrane potential are large enough, they can cause transient tissue damage due to electroporation.

Mechanisms of superiority of ascending ramp waveforms: new insights into mechanisms of shock-induced vulnerability and defibrillation.

Monophasic ascending ramp (AR) and descending ramp (DR) waveforms are known to have significantly different defibrillation thresholds. We hypothesized that this difference arises due to differences in mechanisms of arrhythmia induction for the two waveforms. Rabbit hearts (n = 10) were Langendorff perfused, and AR and DR waveforms (7, 20, and 40 ms) were randomly delivered from two line electrodes placed 10 mm apart on the anterior ventricular epicardium.

The Gurvich waveform has lower defibrillation threshold than the rectilinear waveform and the truncated exponential waveform in the rabbit heart.

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, i.

Structure-function relationship in the AV junction.

In the normal heart, the atrioventricular node (AVN) is part of the sole pathway between the atria and ventricles. Under normal physiological conditions, the AVN controls appropriate frequency-dependent delay of contractions. The AVN also plays an important role in pathology: it protects ventricles during atrial tachyarrhythmia, and during sinoatrial node failure an AV junctional pacemaker can drive the heart.

Optical imaging of the heart.

Optical techniques have revolutionized the investigation of cardiac cellular physiology and advanced our understanding of basic mechanisms of electrical activity, calcium homeostasis, and metabolism. Although optical methods are widely accepted and have been at the forefront of scientific discoveries, they have been primarily applied at cellular and subcellular levels and considerably less to whole heart organ physiology. Numerous technical difficulties had to be overcome to dynamically map physiological processes in intact hearts by optical methods.

Virtual electrode theory explains pacing threshold increase caused by cardiac tissue damage.

The virtual electrode polarization (VEP) effect is believed to play a key role in electrical stimulation of heart muscle. However, under certain conditions, including clinically, its existence and importance remain unknown. We investigated the influence of acute tissue damage produced by continuous pacing with strong current (40-mA, 4-ms biphasic pulses with 4-Hz frequency for 5 min) on stimulus-generated VEPs and pacing thresholds.

Site of origin and molecular substrate of atrioventricular junctional rhythm in the rabbit heart.

During failure of the sinoatrial node, the heart can be driven by an atrioventricular (AV) junctional pacemaker. The position of the leading pacemaker site during AV junctional rhythm is debated. In this study, we present evidence from high-resolution fluorescent imaging of electrical activity in rabbit isolated atrioventricular node (AVN) preparations that, in the majority of cases (11 out of 14), the AV junctional rhythm originates in the region extending from the AVN toward the coronary sinus along the tricuspid valve (posterior nodal extension, PNE).

Nonlinear effects in subthreshold virtual electrode polarization.

Introduction of the virtual electrode polarization (VEP) theory suggested solutions to several century-old puzzles of heart electrophysiology including explanation of the mechanisms of stimulation and defibrillation. Bidomain theory predicts that VEPs should exist at any stimulus strength. Although the presence of VEPs for strong suprathreshold pulses has been well documented, their existence at subthreshold strengths during diastole remains controversial.

Cx43 and dual-pathway electrophysiology of the atrioventricular node and atrioventricular nodal reentry.

Fluorescent imaging has revealed that posterior nodal extensions provide the anatomical substrate for the dual-pathway electrophysiology of the atrioventricular (AV) node during normal conduction and reentry. The reentry can be intranodal, or as well as the posterior nodal extensions, it can involve an endocardial layer of atrial/atrial-nodal (A/AN) cells as part of the AV nodal reentry (AVNR) circuit. Using fluorescent imaging with a voltage-sensitive dye and immunolabeling of Cx43, we mapped the electrical activity and structural substrate in 3 types of AVNR induced by premature atrial stimulation in 8 rabbit hearts.

Mechanisms of make and break excitation revisited: paradoxical break excitation during diastolic stimulation.

Onset and termination of electric stimulation may result in "make" and "break" excitation of the heart tissue. Wikswo et al. (30) explained both types of stimulations by virtual electrode polarization.