Alpha-adrenergic receptor stimulation during simulated ischemia and reperfusion in canine cardiac Purkinje fibers.
We studied the effects of alpha-adrenergic receptor stimulation and calcium on automaticity of isolated canine Purkinje fibers during simulated ischemia and reperfusion. Ischemia included acidosis (pH 6.7), hypoxia (PO2 = 10-25 mm Hg), hyperkalemia (10 mM K+), and either normal or elevated [Ca2+]o (2.7 or 10.8 mM). Control automatic rate and maximum diastolic potential were 18 +/- 2 beats/min and -94 +/- 1 mV, respectively. Simulated ischemia led to depolarization (to -60 +/- 1 mV), cessation of normal automaticity, and in 21% of fibers, bursts of an abnormal automatic rhythm. Phenylephrine, 5 X 10(-8) M, increased the incidence of the automatic rhythm during ischemia to 44%; this effect was blocked by prazosin but not by propranolol. During reperfusion after simulated ischemia at 2.7 mM [Ca2+]o, automatic rhythm and maximum diastolic potential returned toward control values; after simulated ischemia at 10.8 mM [Ca2+]o, automatic rates were greater than those seen after normal Ca2+ ischemia and were associated with sustained membrane depolarization. Phenylephrine (5 X 10(-8) M) at 2.7 mM [Ca2+]o rapidly restored membrane potential during reperfusion, an effect that was blocked by prazosin. At 10.8 mM [Ca2+]o, phenylephrine also restored membrane potential during reperfusion and blunted the increase in reperfusion rate induced by high [Ca2+]o alone. These effects were blocked by propranolol but not by prazosin. Our results show that the effects of phenylephrine on automatic rhythms during simulated ischemia are blocked by alpha-adrenergic receptor antagonists and that rhythms occurring during reperfusion have alpha- and beta-adrenergic receptor components.
Hamra
M
M
Department of Pharmacology, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Rosen
M R
MR
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D004285:Dogs; D006329:Heart Conduction System / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D015425:Myocardial Reperfusion; D010656:Phenylephrine / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects / Q000503:physiopathology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D002118:Calcium