Marked activation delay caused by ischemia initiated after regional K+ elevation in in situ pig hearts

Abstract

Background: Conduction mediated by the slow inward (Ca2+) current occurs in vitro under specific experimental conditions but has not been documented in ventricular muscle in vivo during regional myocardial ischemia, perhaps because certain constituents of ischemia (including hypoxia and acidosis) may inhibit the Ca2+ current in this setting. We hypothesized that slow conduction mediated by the Ca2+ current could occur during acute ischemia in situations in which the extracellular K+ rise was more marked relative to the degree of acidosis, as may occur at ischemic boundaries. Methods and Results: In open-chest, anesthetized swine, an arterial shunt from the carotid artery to the mid-left anterior descending coronary artery was created through which a solution of KCl was infused to raise extracellular K+ ([K+](e)) to approximately 9.4 mmol/L before the initiation of ischemia, which we termed 'K+-modified ischemia.' Ischemia initiated at a normal [K+](e) ('unmodified ischemia') resulted in a mean activation delay in the center of the ischemic zone of 55±26 milliseconds after 5 minutes of ischemia and a decrease in epicardial longitudinal conduction velocity from 53 to 21 cm/s before the onset of conduction block. K+-modified ischemia resulted in a mean activation delay in the center of the ischemic zone of 181±8 milliseconds and a decrease in epicardial longitudinal conduction to less than 10 cm/s. K+-modified ischemia was associated with ventricular fibrillation in 85% of episodes compared with 28% of episodes of unmodified ischemia (P