Tornado in a dish: revealing the mechanisms of ventricular arrhythmias in engineered cardiac tissues.

Ventricular tachycardia and fibrillation (VT/VF) are the leading, immediate causes of death in the developed world. Investigation of the mechanisms of VT/VF spans over a century and a half. However, despite a long and exciting history of discovery in the field, we are still asking the same questions posed by Carl J. Wiggers in 1940 [1]: ‘‘As to the fundamental mechanisms of fibrillation we have plenty of theories, but none is universally accepted. . . we may note in passing that they all center around two ideas, viz., (a) that the impulses arise from centers, or pacemakers, or (b) that the condition is caused by the re-entry of impulses and the formation of circles of excitation. Each of these views, again, has two groups of exponents, viz., (a) those who believe that a single focus, or excitation ring, occurs, and (b) those who favor the idea that multiple foci, or numerous circus rings, are developed.’’ In addition to these fundamental questions, we can also ask: (a) Is VF neurogenic or myogenic in nature? (b) Is VF maintained by the ‘‘mother rotor’’ or ‘‘multiple wavelet’’ mechanism? (c) Is there a ‘‘critical mass’’ of VF? The initial discovery of VT/VF produced by ‘‘faradisation’’ in Carl Ludwig’s laboratory [2] during studies of autonomic control of the heart led to the domination of the neurogenic theory of VF. Yet, subsequent studies of Vulpian [3] and MacWilliam [4] laid to rest the neurogenic theory. They put forward a myogenic theory of VF that remained dominant for over a century. The triumph of this theory was