a-Adrenergic Receptor Stimulation During Simulated Ischemia and Reperfusion in Canine Cardiac Purkinje Fibers

We studied the effects of a-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+], (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` M, increased the incidence of the automatic rhythm during ischemia to 44%; this efrect was blocked by prazosin but not by propranolol. During reperfusion after simulated ischemia at 2.7 mM [Ca2+]L, automatic rhythm and maximum diastolic potential returned toward control values; after simulated ischemia at 10.8 mM [Ca2+1L, automatic rates were greater than those seen after normal Ca2+ ischemia and were associated with sustained membrane depolarization. Phenylephrine (5x 10-8 M) at 2.7 mM [Ca2+]0 rapidly restored membrane potential during reperfusion, an effect that was blocked by prazosin. At 10.8 mM [Ca2+10, phenylephrine also restored membrane potential during reperfusion and blunted the increase in reperfusion rate induced by high [Ca211L 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 a-adrenergic receptor antagonists and that rhythms occurring during reperfusion have a0and P-adrenergic receptor components. (Circulation 1988;78:1495-1502)