[Variations in arrhythmogenic response to catecholamines in acute myocardial ischemia]

Several studies have demonstrated that focal mechanisms contribute to arrhythmogenesis during acute myocardial ischemia in vivo. However, the biochemical derangements during ischemia may either potentiate or depress the electrophysiological mechanisms leading to focal arrhythmias. In the study presented here we have characterized the consequences of various levels of cellular depression and of alterations in the extracellular environment on the development of early (EADs) and delayed (DADs) afterdepolarizations induced by catecholamines. Adult canine myocytes were exposed to: normoxia; hypoxia (pO2 less than 10 mmHg); hypoxia + high K+ or cyanide infusion. Early and delayed afterdepolarizations were induced by alpha or beta adrenergic stimulation in the different experimental conditions by infusing isoproterenol (10(-8)-10(-6) M) or phenylephrine (10(-7)-10(-5) M) + the betablocker nadolol. Hypoxia did not modify EADs or DADs induced by beta stimulation and potentiated DADs induced by alpha stimulation; hypoxia + high K+ blunted DADs induced by both types of stimulation and cyanide infusion completely prevented and suppressed them. Thus, triggered arrhythmias dependent upon adrenergic stimulation can either be potentiated or inhibited by the biochemical derangements of acute ischemia. Focal arrhythmias are more likely to occur in the borderline ischemic cells where cellular depression and extracellular K+ accumulation are less marked.