Despite significant research efforts of investigators in academia, medicine, and the pharmaceutical industry, no effective pharmacological alternative to defibrillation by electric shock has been developed. Thus, defibrillation has evolved to become the only effective therapy against sudden cardiac death. Highly detailed knowledge of ion channel biophysics and cell signaling cascades has allowed for the development of numerous specific agonists and antagonists, but as of yet, has failed to deliver safe and effective antiarrhythmic therapy. In contrast to this approach, electrotherapy is steadily improving its efficacy and safety.

Despite major improvements over the past several decades, defibrillation is not free from side effects, which may include both contractile and electrical dysfunction.1-3 In addition to physical damage to the heart, defibrillation is also associated with psychological side effects.4'5 Therefore, reduction of defibrillation energy is highly desirable. However, the basic mechanisms of defibrillation still remain debatable a century after its inception, which has slowed further improvement of the therapy. This chapter explores one of the leading hypotheses of defibrillation, the virtual electrode hypothesis, which has emerged over the past decade through the successes of novel research methodologies, including optical mapping and bidomain modeling.

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