Alpha 1-adrenoceptor regulation of delayed afterdepolarizations and triggered activity in subendocardial Purkinje fibers surviving 1 day of myocardial infarction

Abstract

Alpha 1-adrenoceptor agonists were shown to induce delayed afterdepolarizations (DADs) and triggered activity in the presence of elevated extracellular Ca 2+. We investigated the effects of alpha 1-adrenoceptor stimulation on DADs and triggered activity in canine Purkinje fibers that survived 1-day of myocardial infarction. Endocardial preparations were studied using standard microelectrode techniques. In quiescent preparations showing no DADs and in presence of propranolol (2 × 10 −7 m), phenylephrine (10 −6 m), an alpha 1-adrenoceptor agonist induced DADs ( n = 6) and differentially induced triggered activity in ischemic but not in normal Purkinje fibers ( n = 4). In 8 preparations that showed subthreshold DADs, phenylephrine increased the DAD amplitude from 4.0 ± 2.5 mV to 8.0 ± 3.3 mV ( P < 0.03) and from 3.2 ± 1.5 mV to 6.5 ± 3.7 mV ( P < 0.05) at paced cycle lengths of 800 and 400 ms, respectively. Phenylephrine caused subthreshold DADs to reach threshold and result in triggered activity ( n = 6). The effects of phenylephrine were abolished by 10 −6 m prazosin, an alpha 1-adrenoceptor blocker. Our results suggest that alpha 1-adrenoceptor stimulation regulates DADs and triggered activity seen in subendocardial Purkinje fibers surviving 1 day of myocardial infarction and may contribute to the spontaneous ventricular tachycardia seen in vivo at this stage.