Developmental differences in the electrophysiological response of isolated canine Purkinje fibers to adrenergic stimulation during simulated ischemia.
Developmental differences in adrenergic responsiveness may cause age-related changes in the cellular response to ischemia. Standard microelectrode techniques were used in isolated young and adult canine Purkinje fibers to determine the effect of simulated ischemia ([K+]o = 10 mM, pH 6.7, pO2 < 25 mm Hg) alone or with adrenergic stimulation on the rhythmic activity in spontaneously beating Purkinje fibers and on transmembrane potentials and delayed afterdepolarizations in paced Purkinje fibers (basic cycle length = 800-300 ms). The adrenergic agonists used were phenylephrine (5 x 10(-8) M) and isoproterenol (1 x 10(-6) M). For all automatic fibers studied, the control maximum diastolic potential in adults (-96 +/- 1 mV, n = 37) and in the young (-98 +/- 1 mV, n = 36) went to -62 +/- 1 mV during ischemia in both groups and returned to -96 +/- 2 mV with reperfusion. The incidence of rhythmic activity (expressed as percent) during ischemia alone was similar at both ages: adults, 22%; young, 25%. The incidence of ectopic activity with phenylephrine superfusion during ischemia for adults was 63%, an effect blocked by prazosin (1 x 10(-6) M) but not by propranolol (2 x 10(-7) M); the incidence for the young was 25%. Isoproterenol caused ectopic rhythms in 86% of young fibers and 17% of adult fibers (p < 0.05 young vs. adult). During reperfusion the return to control rhythm was slower in adults after ischemia alone or ischemia + alpha-adrenergic stimulation with phenylephrine. There were no age-related differences in the transmembrane potential response of paced fibers to ischemia or reperfusion, and there were no delayed afterdepolarizations with interruption of pacing at 800, 500, or 300 ms in either group. These data suggest that age-related differences in adrenergic responses alter the cellular response to an ischemic insult. To the extent that an ectopic beat may initiate an abnormal rhythm, these differences in sensitivity to adrenergic agonists may lead to developmental differences in arrhythmogenic potential during ischemia.
Fenrich
A
A
Department of Pediatrics, Baylor College of Medicine, Houston, Tex.
Hamra
M
M
D000200:Action Potentials / Q000187:drug effects; D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D011690:Purkinje Fibers / Q000187:drug effects* / Q000254:growth & development*; D013268:Stimulation, Chemical
D018663:Adrenergic Agents