ALTERATIONS IN REPOLARIZATION OF CARDIAC PURKINJE-FIBERS RECOVERING FROM ISCHEMIC-LIKE CONDITIONS - GENESIS OF EARLY AFTERDEPOLARIZATIONS

Introduction: Triggered activity initiated from delayed after depolari zations has been proposed as a possible cause of arrhythmias during re perfusion of ischemic myocardium. However, the potential for abnormal repolarization and early afterdepolarizations (EADs) to develop under similar conditions has not been fully explored. Methods and Results: R epolarization of the cell membrane during recovery from ischemic-like conditions was analyzed from transmembrane recordings in isolated rabb it Purkinje fibers paced at different basic cycle lengths. Preparation s were exposed to conditions of hypoxia (defined as oxygen tension < 3 0 mmHg, high potassium, and zero substrate) plus lactic acidosis (pH 6 .7) for 45 minutes followed by recovery in normal Tyrode's solution. C ompared to control, action potentials during recovery at basic cycle l ength of 3,000 msec (n = 11) were characterized by a: (1) -7.2 +/- 2.1 mV shift in plateau potential (P < 0.01); (2) 126.1 +/- 63.6 msec inc rease in plateau duration (P < 0.05); and (3) 0.29 +/- 0.07 V/sec slow ing of the maximum rate of terminal repolarization (phase 3; P < 0.01) . These changes were larger when 10 to 20 muM amiloride was added to t he hypoxic, acidotic test solution but were smaller when tissues were conditioned with hypoxia alone (zero lactate, pH 7.4). Following hypox ia plus acidosis, with or without amiloride, repolarization at long ba sic cycle lengths was often accompanied by EADs predominantly generate d from potentials positive to -40 mV. These afterpotentials were block ed by Ca2+ channel antagonists and exhibited an activation threshold o f -26.3 +/- 1.8 mV (n = 7). Conclusion: These data are consistent with the hypothesis that the combined negative voltage shift in the platea u and increase in its duration lead to the genesis of low membrane pot ential EADs by allowing reactivation of Ca2+ channels. Moreover, these results suggest that bradycardia-dependent EADs in Purkinje tissue ma y underlie arrhythmias in the intact heart during reperfusion of ische mic myocardium by mechanisms that are related in part to the acidosis established during the preceding ischemic conditions.