Ventricular fibrillation is the most important immediate cause of sudden cardiac death, which is the main source of mortality in developed countries. Currently, the only practical method for treating ventricular fibrillation is electrical defibrillation. External defibrillators accessible to public and implantable devices are becoming more widespread, reducing the risk of sudden cardiac death. Nevertheless, current defibrillation techniques have significant drawbacks. Shocks can be detrimental by causing pain, tissue damage, and reinducing arrhythmias.1 In addition, shocks may fail, which requires multiple shock application,2 or fibrillation can be terminated but normal heartbeat and blood circulation not restored.3,4 Therefore, there is a need to increase defibrillation efficacy and reduce its side effects, which underlies the continuing search for better defibrillation techniques. This search would have higher chances for success if it were guided by the exact knowledge of the defibrillation mechanism. Significant advances in understanding defibrillation were made in recent years using sophisticated electrical and optical mapping techniques as well as advanced mathematical models of cardiac excitation that provided a wealth of new information about the effects of electrical fields on cardiac tissue. Despite these efforts the defibrillation mechanism still remains a mystery. One of the main unresolved questions is why an electrical shock causes any significant effect on the heart at all; the other question is how exactly the shock affects the heart and stops abnormal electrical activity. Fibrillation is generally considered a distributed process, which is maintained by multiple reentrant circuits or randomly wandering wavelets in various parts of the heart.5-7 To interrupt such fibrillation, all reentrant wavefronts have to be extinguished. According to the excitatory hypothesis of defibrillation, this is achieved by simultaneous activation of cardiac tissue in the excitable and relatively refractory states.8,9 The newly depolarized tissue presents functional obstacles to excitation waves, blocking their propagation and, therefore, arresting fibrillation. An important requirement of defibrillation is that abnormal activity must be stopped in a critical mass of ventricular myocardium estimated at 80-90% of the total mass.9,10 This means that the shock must change membrane potential (V m) of nearly all cardiac cells across the ventricular wall. How this global shock effect is achieved is not presently known. The classical cable model of cardiac muscle indicates that shock-induced V m changes should be restricted only to the tissue near shock electrodes or muscle surface,11 leaving the intramural bulk of the myocardium unaffected by the shock. This model's prediction about the locality of shock effects is in stark contradiction with the distributed nature of fibrillation. This contradiction was recognized about 20 years ago. 12-14 To resolve it, a so-called secondary source hypothesis was proposed, which linked shock effects with the microscopic tissue structure. More specifically, it was postulated that shocks cause widespread changes of V m due to numerous microscopic discontinuities in the tissue structure, such as cell boundaries.12-14 © 2009 Springer US.