Background. The mechanisms underlying repetitive activity during reperfusion of ischemic myocardium are thought to include triggered responses elicited at short pacing cycle lengths. The potential to generate repetitive responses at longer pacing cycle lengths under similar conditions, however, has not been explored. Thus, the present study examined the role of cycle length on the cellular electrical changes produced during recovery from ischemic-like conditions and identified the major component precipitating nondriven, repetitive activity. Methods and Results. Transmembrane potentials were recorded in vitro from isolated rabbit Purkinje fibers exposed to hypoxia (defined as Po2<30 mm Hg, high [K+]0, and zero glucose) plus lactic acidosis (pH 6.7) for 45 minutes and during recovery in normal Tyrode's solution (pH 7.4). Compared with control, action potential duration (90% repolarization) during recovery increased transiently by 40.9±11.8 and 241.0±51.1 msec at respective basic cycle lengths of 1,000 and 3,000 msec (both p<0.005). In 81% of preparations, action potential prolongation was accompanied by early afterdepolarizations and triggered activity generated from low (positive to -40 mV) or high (negative to -40 mV) membrane potentials. In 62% of experiments, brief periods of abnormal automaticity also occurred. Triggered responses were 1) unaffected by 1 μg/ml anodine, 2) abolished by pacing at short basic cycle lengths or by exposing tissues to 2.5 μg/ml lidocaine, and 3) more easily induced at long basic cycle lengths or by superfusing 2.5 μg/ml quinidine. When tissues were conditioned with hypoxia alone (pH 7.4), action potential prolongation on recovery was comparatively small, and nondriven responses did not develop. Conversely, addition of 10-20 μM amiloride to the hypoxic, acidic test solution augmented recovery-induced action potential prolongation. Conclusions. We conclude that acidosis, as a component of ischemia, plus slow pacing frequencies may mediate the genesis of early afterdepolarizations and triggered activity in Purkinje fibers on recovery, long after extracellular pH has been restored to normal. These data may have clinical relevance to the mechanisms of reperfusion arrhythmias in the intact human heart.
- Early afterdepolarizations
- Purkinje fibers
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)