Reperfusion Arrhythmias and Sudden Cardiac Death

Abstract

The observation that ventricular fibrillation may occur within seconds after restoration of blood flow to myocardium turned ischemic by a period of coronary occlusion (reperfusion) was originally made in the experimental laboratory in the 19th century by Cohnheim and Von Schulthess-Rechberg1 and later confirmed in the early 20th century by Tennant and Wiggers.2 In fact, it was found in subsequent laboratory experiments that ventricular fibrillation may occur more frequently after reperfusion than after coronary artery occlusion.3 It took until the latter part of the 20th century for these early laboratory studies to be translated to clinical medicine. It was noticed that only a minority of those individuals who have been successfully resuscitated from sudden ventricular fibrillation associated with coronary artery disease subsequently developed a myocardial infarction,4,5 suggesting that, if indeed myocardial ischemia caused by coronary occlusion was involved, it was transient. Reperfusion must have occurred. This proposed relationship between transient ischemia, reperfusion, and arrhythmias was corroborated by studies in patients with transient coronary artery spasm in whom ventricular arrhythmias, including ventricular fibrillation, occurred within minutes after the beginning of electrocardiographic signs of myocardial ischemia caused by the spasm6 but also after ST segment changes had returned to normal, when reperfusion had occurred.6–9 What is the mechanism responsible for this occurrence of fibrillation? This is a subject that has been pursued in more than a century of experimentation with slow but continued progress. The most recent advance, now in the 21st century, is the article by Cascio et al10 in this issue of Circulation Research . The initial information on mechanisms of reperfusion arrhythmias came from experiments on in situ hearts of large animals subjected to periods of coronary artery occlusion followed by release of the occlusion that allowed reperfusion. In these experiments, the …