title: Mechanisms of ventricular arrhythmias in acute ischemia and reperfusion.
abstract: Coronary occlusion leading to nearly total absence of myocardial perfusion is the major cause of lethal ischemic arrhythmia in humans. In this setting, intracellular acidosis rapidly develops and leads to accelerated K+ efflux from the myocyte. Other metabolites, including lipid amphiphiles such as LPC, also rapidly accumulate in the ischemic zone. Elevated extracellular K+ and LPC cause membrane depolarization, which leads to slow conduction and increased refractoriness. These electrophysiologic changes contribute to the development of re-entrant rhythms, which predominate during early ischemia (phase 1a). Diffusion of extracellular K+ from the ischemic zone and release of endogenous catecholamines result in improvement in electrophysiologic parameters and are associated with a short arrhythmia-free interval, which occurs approximately 10 minutes after coronary occlusion. A second phase of arrhythmia (1b) then occurs and may be due in part to catecholamine-mediated triggered activity. Irreversible cell injury occurs 15 to 20 minutes after coronary occlusion and is associated with cell Ca++ overload, loss of gap junctions, and impaired cell coupling. This may lead to re-entrant arrhythmias. Reperfusion of ischemic myocardium leads to arrhythmia predominantly mediated by non re-entrant mechanisms. In humans, these reperfusion arrhythmias are usually relatively benign.
authors.forename: S P
authors.initials: SP
authors.lastname: Sedlis
mesh_terms: D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D003327:Coronary Disease / Q000150:complications* / Q000378:metabolism; D004594:Electrophysiology; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006329:Heart Conduction System / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D050356:Lipid Metabolism; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D011188:Potassium / Q000378:metabolism
chemical_list: D005947:Glucose; D011188:Potassium