ELECTROPHYSIOLOGICAL EFFECTS OF DEFIBRILLATION SHOCKS

The objective of this study is to understand the process of defibrillation by electrical shocks. It has been known for nearly a century that such shocks can terminate the deadly arrhythmia of ventricular fibrillation and promptly restore the heart to its normal rhythm. Electrical defibrillation has been widely used during the past several decades to treat this fatal malady. Despite the already essential role that electrical defibrillation plays in the prevention of sudden death there remains much to be learned about how electrical shocks terminate fibrillation. With the introduction of implantable defibrillators it is certain that this technique will be applied among an even wider patient population. It is therefore essential that we understand how electrical defibrillation works, not only to improve the design of implantable devices, but to also predict the circumstances in which it is best applied, its likely interactions with anti-arrhythmic drugs and to improve the safety and efficacy of the defibrillation process. Electrical defibrillation can be described as a sequence of discrete events: a shock gives rise to membrane voltage changes which in turn elicit electrophysiological responses that ultimately extinguish fibrillation wavefronts and restore the ventricle to electrical stability. This proposal aims to examine hypotheses concerning each of these steps. A perfused papillary muscle preparation will be used in conjunction with a voltage sensitive dye to optically record the cardiac action potential. This experimental preparation will permit the electrical interaction between the applied electrical field of the shock and the myocardial architecture to be studied in detail. The voltage sensitive dye technique permits uninterrupted recordings of cardiac electrical activity to be made in the presence of electrical shocks. The first specific aim is to test the predictions made by a linear cable model of the effects of electrical shocks on cardiac membrane potential and to see whether and how this hypothesis should be updated. The second aim is to elucidate the passive and active responses of the myocardial membrane to electrical shocks. It has been shown that not only do shocks stimulate action potentials but, when applied during the action potential plateau phase, that they also prolong the duration of the depolarized state. Neither the mechanism nor the ramifications of this latter action are known. The last specific aim is to describe in detail the process of wavefront extinction by defibrillation shocks. It has long been a central tenet of all defibrillation hypotheses that the elimination of most or all fibrillation wavefronts is essential for terminating fibrillation. While this process can be easily envisioned and ample evidence suggests that it occurs, it has not yet been demonstrated in detail. This proposal builds on the principle investigator's earlier work using voltage sensitive recording to study electrical defibrillation and is expected to yield valuable information regardless of which hypothesis proves correct.