The Role of Phase Singularities in Determining Defibrillation Efficacy

Ventricular fibrillation (VF) is the most common cause of death in adults under the age of 65. The chaotic propagation of electrical activation wavefronts which characterize VF can be terminated by a strong electric shock. This therapy is often given by an implantable cardioverter/defibrillator (ICD) which has been shown to be more effective than antiarrhythmic drugs in preventing sudden death in a high risk patient population. While advances have been made in ICD therapies, the basic mechanisms by which these devices terminate an episode of VF are not well understood.

Investigations using experimental and computational techniques revealed that defibrillation shocks induce patterns of membrane hyperpolarization and depolarization on the surface of the heart. Further studies demonstrated how these patterns of membrane polarization depend upon the interactions between shock induced electric fields and tissue structure. However, neither the experiments nor current state-of-the-art models have been able to examine the myocardial tissue volume during VF and defibrillation, and neither can identify phase singularities at the core of the reentrant pathways. We propose to create a computational model which will allow detailed investigation of these quantities and their role in defibrillation.

Our specific aims are:

1. To develop and validate a computationally efficient, physiologically and anatomically accurate defibrillation model of the rabbit ventricles,

2. To identify the organizing centers of reentrant activity that cause defibrillation shocks to fail,

3. To provide mechanistic interpretations of experimental observations,

4. To evaluate the effects of pre- and postshock stimulation protocols on shock success.

Our research will provide important new insights into the process of defibrillation. It will reveal the factors which cause shocks to fail within the three dimensional volume of the heart and suggest future directions for advancements in defibrillation procedures. Ultimately, gaining these insights will lead to safer and more effective ICD designs for patients at risk of VF.