Stephen M. Dillon

Optical recordings in the rabbit heart show that defibrillation strength shocks prolong the duration of depolarization and the refractory period.

The present data were obtained using the technique of optical recording with the voltage-sensitive dye WW781. This technique, unlike electrical methods, was able to provide uninterrupted recordings free of artifacts during defibrillation shocks. Optical recordings were made from sites on the ventricular epicardium of perfused rabbit hearts during electrical pacing. Continuous recordings of the electrophysiological responses of an intact heart to defibrillation threshold-strength shocks were made. It was shown that these shocks were able to stimulate normal-appearing action potentials in nonrefractory myocardium. A new and unexpected finding was that defibrillation threshold-strength shocks were also able to evoke a sustained, depolarizing response from myocardium already undergoing an action potential. This prolonged the time that the myocardium remained in the depolarized state. Prolongation of the depolarized state was accompanied by an equal prolongation of the refractory period. There was no indication that this depolarizing shock response was due to damage of the myocardium by the shock, to heterogeneous electrical responses in the optical recording area, or to the methods used in this study. It is hypothesized that these shocks were able to elicit a new action potential in already depolarized myocardium by hyperpolarizing portions of the myocardiums cellular membranes and, in so doing, to reactivate the fast sodium current. This effect, if prevalent in a fibrillating ventricle, could play a role in the defribillation process by effectively resynchronizing electrical activity.

Synchronized repolarization after defibrillation shocks. A possible component of the defibrillation process demonstrated by optical recordings in rabbit heart.

BackgroundIt is currently believed that defibrillation shocks act primarily by stimulating excitable myocardium to abolish wave fronts. Recent studies have shown that shocks applied during pacing not only stimulate excitable myocardium but also prolong the depolarization and refractoriness of myocardium already in a depolarized state. This study investigates the effects of shocks on fibrillation action potentials. Methods and ResultsRecordings of membrane action potentials free of shock artifact were obtained using the voltage-sensitive dye WW781 during defibrillation of isolated rabbit hearts. These records showed that the shocks caused an additional phase of depolarization beginning with an initial rapid depolarization of the optical signal followed by a slow phase of repolarization. This occurred throughout all phases of the fibrillation action potential from just after completion of the upstroke to a time of near maximal repolarization. Defibrillation shocks, however, had the additional effect of causing the myocardium to repolarize at a constant time after the shock regardless of its prior electrical activity-the constant repolarization time response. This effect was not dependent on the presence of D600 (methoxyverapamil) or continuous coronary perfusion. It was accompanied by a similar constancy in the return of myocardial excitability. Recordings taken from multiple adjacent recording sites also showed a constant repolarization time among them. ConclusionsA simple model of reentry is used to illustrate how the constant repolarization response, in addition to wave front termination and refractoriness extension, could play a role in the successful termination of fibrillation by electrical shock.

Shock-Induced Depolarization of Refractory Myocardium Prevents Wave-Front Propagation in Defibrillation

The elimination of most, if not all, propagating wave fronts of electrical activation by a shock constitutes a minimum prerequisite for successful defibrillation. However, the factors responsible for the prevention of postshock propagating activity are unknown. We investigated the determinants of this effect of defibrillation shocks in 23 Langendorff-perfused rabbit hearts by optically mapping cardiac cellular electrical activity by means of laser scanning. The optical action potentials obtained by this method were continuously recorded from 100 ventricular epicardial sites before, during, and after shock delivery during fibrillation. Analysis of activation maps showed that postshock propagating activity arose from areas depolarized by the shock. In 273 shock episodes, 898 sites at the border of shock-depolarized areas (BSDAs) from which wave-front propagation could have arisen were identified. The incidence of postshock propagation from BSDA sites was inversely related to refractoriness, as indexed by coupling interval (CI) or the optical takeoff potential (Vm). Specifically, there was a near-zero probability of postshock propagation if the shock caused depolarization at CIs < 50% of the fibrillation cycle length or from myocardium still depolarized to > or = 60% of the amplitude of a paced action potential (APA). Furthermore, incidences of wave-front propagation following shocks were consistently lower than the propagation incidences of naturally occurring unshocked fibrillation wave fronts, at comparable CIs and Vms. We conclude that the incidence of postshock wave-front propagation decreases with increasing refractoriness at the BSDA and that shock-induced depolarization of effectively refractory myocardium (ie, depolarized to > or = 60% APA) is required to guarantee the cessation of continued wave-front propagation in defibrillation.

Anisotropic reentry in the epicardial border zone of myocardial infarcts.

In a currently used classification of arrhythmogenic mechanisms, there are two major classes of reentry-anatomical and functional. The former is dependent on anatomically defined reentrant pathways that may course around an obstacle as originally shown in Mines”-* and Garrey’s3 studies on excised rings of cardiac muscle. It is exemplified in the intact heart by bundle branch reentry,4 reentry utilizing an accessory AV pathway in the preexcitation syndrome5 and reentry in the ring of muscle around the tricuspid valve causing atrial flutter.6 On the other hand, functional reentry is dependent on heterogeneities of the electrophysiological properties of the cardiac fibers caused by local differences in the transmembrane action potentials, for example, resting potentials, time course of repolarization, and recovery of excitability. It does not require an anatomically defined reentrant pathway. The mechanism for functional reentry that has been characterized in the most detail is the “leading circle mechanism” that can occur in normal atrial tissue.’ Recent studies indicate that the anatomy of cardiac muscle may be important for reentry in a way other than simply providing a road over which the reentrant impulse travels. Anatomy may participate in determining functional properties of cardiac muscle, since the structural characteristics of heart muscle can influence both conduction and refractor ine~s.~.~ These structural characteristics include the orientation of the myocardial fibers and the way the fibers or bundles of fibers are connected to each other. The influence of structure on functional properties is described by the concept of anisotropy (see paper by Spach et al., this volume).

Overdrive stimulation of functional reentrant circuits causing ventricular tachycardia in the infarcted canine heart. Resetting and entrainment.

Background. Clinical electrophysiology studies have used, for the most part, models of anatomic reentrant circuits to explain entrainment of ventricular tachycardia. Our studies use activation maps to directly determine mechanisms of entrainment of functional circuits that cause tachycardia. Methods and Results. Electrograms were recorded from 192 sites on reentrant circuits in the epicardial border zone of canine myocardial infarcts during sustained ventricular tachycardia. Overdrive stimulation from different sites and at different cycle lengths was investigated. The reentrant circuits were shown to be functional, yet stimulated impulses could enter and repetitively reset the circuits (entrainment), demonstrating the presence of an excitable gap. Entrainment could occur from different stimulation sites with the stimulated impulses from each site activating the circuit with a different pattern. Entrainment, however, did not occur when the stimulated wave fronts obliterated the lines of functional block in the circuit. Fusion on the ECG occurred during entrainment when the stimulated impulses activated the ventricles concurrently with a previous stimulated impulse leaving the reentrant circuit at a different site. The first postpacing QRS was captured but not fused because it was caused by the last stimulated impulse emerging from the circuit. The first postpacing cycle length on the ECG was either equal to or longer than the overdrive cycle length depending on whether there was a fusion QRS during overdrive. The first postpacing cycle length at sites in the reentrant circuit equaled the pacing cycle length. At an appropriately short overdrive cycle length, stimulated impulses blocked in the circuit to terminate reentry. Conclusions. Functional reentrant circuits causing ventricular tachycardia can be reset and entrained. Activation maps directly show the mechanisms. (Circulation 1993;87:1286‐1305)

Prolongation of Ventricular Refractoriness by Defibrillation Shocks May be Due to Additional Depolarization of the Action Potential

Shock‐Induced Refractoriness Prolongation in Canines. Introduction: A comparison of the effects of shock timing and strength on the effective refractory periods (ERPs) of open chest canine hearts to the duration of depolarization in optically recorded action potentials from the rabbit heart was conducted in order to investigate the mechanism of ERP prolongation in the canine.

Effects of Pinacidil on Electrophysiological Properties of Epicardial Border Zone of Healing Canine Infarcts Possible Effects of K ATP Channel Activation

Background—KATP channels, activated by ischemia, participate in the arrhythmogenic response to acute coronary occlusion. The function of these channels in border zones of healing infarcts, where arrhythmias also arise, has not been investigated. Do these channels remain maximally activated during infarct healing, or do they downregulate after a period of time? Both might preclude further activation. Methods and Results—Myocardial infarction was produced in dogs by ligation of the left anterior descending coronary artery. Impulse propagation in the epicardial border zone (EBZ) of 4-day-old healing infarcts was mapped during administration of pinacidil, a KATP channel activator, directly into the EBZ coronary blood supply. Pinacidil restored conduction and excitability when the EBZ was initially inexcitable and had large regions of block (6 of 8 experiments). This allowed reentrant circuits to form in the EBZ, causing tachycardia (4 of 8 experiments ). In hearts with an initially excitable EBZ, pinacidil shortened the effective refractory period and abolished conduction block at short cycle lengths (7 experiments). This effect prevented initiation of reentry (1 of 2 experiments). Conclusions—The response to pinacidil indicates that KATP channels in the EBZ remain functional and can be activated to influence electrophysiological properties and arrhythmogenesis.

Reentrant Circuits and the Effects of Heptanol in a Rabbit Model of Infarction with a Uniform Anisotropic Epicardial Border Zone

Reentry in Rabbit Ventricles. Introduction: The purpose was to study reentry in a rabbit model of infarction.

Characterization of the Excitable Gap in Human Type I Atrial Flutter

OBJECTIVES We sought to characterize the excitable gap of the reentrant circuit in atrial flutter. BACKGROUND The electrophysiologic substrate of typical atrial flutter has not been well characterized. Specifically, it is not known whether the properties of the tricuspid valve isthmus differ from those of the remainder of the circuit. METHODS Resetting was performed from two sites within the circuit: proximal (site A) and distal (site B) to the isthmus in 14 patients with type I atrial flutter. Resetting response patterns and the location where interval-dependent conduction slowing occurred were assessed. RESULTS Some duration of a flat resetting response (mean +/- SD 40.1 +/- 20.9 ms, 16 +/- 8% of the cycle length) was observed in 13 of 14 patients; 1 patient had a purely increasing response. During the increasing portion of the resetting curve, interval-dependent conduction delay most commonly occurred in the isthmus. In most cases, the resetting response was similar at both sites. In three patients, the resetting response differed significantly between the two sites; this finding suggests that paced beats may transiently change conduction within the circuit or the circuit path, or both. CONCLUSIONS Some duration of a flat resetting response was observed in most cases of type I atrial flutter, signifying a fully excitable gap in all portions of the circuit. The isthmus represents the portion of the circuit most vulnerable to interval-dependent conduction delay at short coupling intervals.

Effects of High and Low Shock Energies on Sinus Electrograms Recorded via Integrated and True Bipolar Nonthoracotomy Lead Systems

Effects of Shock Energies on Electrograms. Introduction: The purpose of this investigation was to prospectively evaluate the voltage‐ and time‐dependent characteristics of a biphasic defibrillator discharge on the amplitude of the rate sensing electrogram recorded from two “integrated” and one true bipolar nonthoracotomy lead system. Prolongation of redetection time has been noted after a failed first shock with nonthoracotomy lead systems. However, prospective evaluation of the time‐ and voltage‐dependent effects of biphasic shocks on electrogram amplitude with clinically utilized lead systems has not been systematically performed.