Mechanisms of Defibrillation Failure

Since defibrillation by high-energy electric shocks is the only effective means for termination of ventricular fibrillation, defibrillation shocks are now widely used in clinical practice for prevention of sudden cardiac death. However, the high-energy shocks could result in myocardial dysfunction and damage (Runsio et al., 1997) and in psychological trauma (Maisel, 2006). Comprehensive understanding of the ventricular response to electric shocks as well as the mechanisms of defibrillation failure is the approach most likely to succeed in reducing shock energy. Recent experimental techniques, such as high-resolution mapping with multi-electrodes or optical recordings, have provided new characterizations of tissue responses to electric shocks. However, the mechanisms of the success and failure of defibrillation are not fully understood since the presently available experimental techniques, which provide detailed information about the myocardial surface (mostly epicardial) activity, are insufficient in resolving depth information during and after the electric shocks. Moreover, electrical or optical signal artifacts during the shock make it difficult for the researchers to get direct evidence regardig the mechanisms of electrical defibrillation. It has been demonstrated experimentally that after the delivery of shocks of strength near the defibrillation threshold (DFT) from an implantable cardioverter-defibrillator (ICD) device, the first global activation consistently arises focally on the left ventricle (LV) (Chattipakorn et al., 2001, 2003) following an isoelectric window (a quiescent period following the shock). Understanding the origins of the isoelectric window is thus of great importance for uncovering the mechanisms of defibrillation failure. Various hypothesis have been proposed for the existence of the isoelectric window, including virtual electrodeinduced propagated graded response (Trayanova et al., 2003), calcium sinkholes (Hwang et al., 2006), and activations emanating from Purkinje fibers (Dosdall et al., 2007); however, the mechanisms responsible for it remain inconclusive. In this context, we hypothesized that submerged “tunnel propagation” of postshock activation (PA) through shock-induced intramural excitable areas underlies both fibrillation induction and failed defibrillation by shocks as well as the existence of an isoelectric window. To test this hypothesis, we analyzed the global three-dimensional activity in ventricles with the use of a recently-developed realistic computer model of stimulation/defibrillation in the rabbit heart (Trayanova et al., 2002). Simulations with this