Progressive depolarization: a unified hypothesis for defibrillation and fibrillation induction by shocks.

Experimental studies of defibrillation have burgeoned since the introduction of the upper limit of vulnerability (ULV) hypothesis for defibrillation. Much of this progress is due to the valuable work carried out in pursuit of this hypothesis. The ULV hypothesis presented a unified electrophysiologic scheme for linking the processes of defibrillation and shock-induced fibrillation. In addition to its scientific ramifications, this work also raised the possibility of simpler and safer means for clinical defibrillation threshold testing. Recent results from an optical mapping study of defibrillation suggest, however, that the experimental data supporting the ULV hypothesis could instead be interpreted in a manner consistent with traditional views of defibrillation such as the critical mass hypothesis. This review will describe the evidence calling for such a reinterpretation. In one regard the ULV hypothesis superseded the critical mass hypothesis by linking the defibrillation and shock-induced fibrillation processes. Therefore, this review also will discuss the rationale for developing a new defibrillation hypothesis. This new hypothesis, progressive depolarization, uses traditional defibrillation concepts to cover the same ground as the ULV hypothesis in mechanistically unifying defibrillation and shock-induced fibrillation. It does so in a manner consistent with experimental data supporting the ULV hypothesis but which also takes advantage of what has been learned from optical studies of defibrillation. This review will briefly describe how this new hypothesis relates to other contemporary viewpoints and related experimental results.

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.

Animated images of cardiac membrane voltage during defibrillation.

Optical recording using voltage-sensitive dyes has been used to investigate the mechanisms of defibrillation because it (1) is immune to the artifacts produced by high-voltage shocks, (2) provides the time course of the membrane action potential, and (3) can be used to make simultaneous recordings at many sites. The authors used the laser scanning technique to optically record action potentials from 100 sites with 1-ms resolution on the surface of the isolated, perfused rabbit heart during defibrillation. The data were typically analyzed by constructing maps of impulse propagation and examining individual recordings from sites of interest. Described here is a new analysis method that creates millisecond-by-millisecond images of the spatial distribution of membrane potentials. The experimental protocol applied a test shock to the fibrillating heart, followed by a rescue shock and a paced beat. Optical recordings were calibrated to yield membrane voltage as a percentage of the resting and overshoot levels of the postrescue stimulated action potential. The positions of the recording sites and the membrane voltage levels for all 100 sites during a single 1-ms interval were used to interpolate membrane voltage levels at points within a 128 x 128 pixel frame using the biharmonic interpolation method. The level of membrane potential was encoded by pixel color and surface elevation. Sequential frames were viewed as a face-on two dimensional or as a three-dimensional perspective of the colored surface. Animation of membrane voltage distributions enabled the visualization of the interaction between the shock-induced electrophysiologic response and the propagation of electrical activity preceding and following a defibrillation shock. Successful defibrillation shocks synchronized repolarization across the surface of the heart following the shock.