Alterations in Repolarization of Cardiac Purkinje Fibers Recovering from Ischemic‐like Conditions:

Abstract

Triggered activity initiated from delayed after-depolarizations has been proposed as a possible cause of arrhythmias during reperfusion of ischemic myocardium. However, the potential for abnormal repolarization and early afterdepolarizations (EADs) to develop under similar conditions has not been fully explored. Repolarization of the cell membrane during recovery from ischemic-like conditions was analyzed from transmembrane recordings in isolated rabbit Purkinje fibers paced at different basic cycle lengths. Preparations were exposed to conditions of hypoxia (defined as oxygen tension < 30 mmHg, high potassium, and zero substrate) plus lactic acidosis (pH 6.7) for 45 minutes followed by recovery in normal Tyrode's solution. Compared to control, action potentials during recovery at basic cycle length 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 increase in plateau duration (P < 0.05); and (3) 0.29 +/- 0.07 V/sec slowing of the maximum rate of terminal repolarization (phase 3; P < 0.01). These changes were larger when 10 to 20 microM amiloride was added to the hypoxic, acidotic test solution but were smaller when tissues were conditioned with hypoxia alone (zero lactate, pH 7.4). Following hypoxia plus acidosis, with or without amiloride, repolarization at long basic cycle lengths was often accompanied by EADs predominantly generated from potentials positive to -40 mV. These afterpotentials were blocked by Ca2+ channel antagonists and exhibited an activation threshold of -26.3 +/- 1.8 mV (n = 7). These data are consistent with the hypothesis that the combined negative voltage shift in the plateau and increase in its duration lead to the genesis of low membrane potential EADs by allowing reactivation of Ca2+ channels. Moreover, these results suggest that bradycardia-dependent EADs in Purkinje tissue may underlie arrhythmias in the intact heart during reperfusion of ischemic myocardium by mechanisms that are related in part to the acidosis established during the preceding ischemic conditions.