In vitro electrophysiologic properties of amrinone in mammalian cardiac tissue

We studied the actions of amrinone on transmembrane electrical activity in isolated normal and physiologically compromised mammalian cardiac Purkinje and ventricular tissues. No arrhythmogenic effects of amrinone were identified in canine Purkinje tissue superfused with concentrations of 18.7 and 187 micrograms/ml (10(-4) and 10(-3) M) or in feline papillary tissue at concentrations of 18.7 and 56.1 micrograms/ml (10(-4) and 3 X 10(-4)M). In K+-depolarized canine Purkinje tissue, amrinone at 100 micrograms/ml (5.3 X 10(-4) M) failed to restore excitability; however, in norepinephrine-activated, K+-depolarized Purkinje tissue, amrinone significantly increased slow potential upstroke velocity and action potential amplitude and duration at doses ranging from 10 to 300 micrograms/ml. In K+-depolarized canine trabecula carneae, amrinone initiated slow potentials in the absence of norepinephrine and produced dose-dependent increases in slow potential upstroke velocity and in action potential amplitude and duration over a dose range of 30-300 micrograms/ml. Amrinone at 100 micrograms/ml did not influence transmembrane electrical activity of Purkinje tissue with tetracaine-depressed Na+-channel function. Amrinone did not produce oscillatory afterpotentials, influence ouabain-induced afterpotentials, or alter overdrive-induced depolarization. Amrinone caused no distinctly arrhythmia-producing effects in a heterogeneous population of depolarized canine Purkinje tissues removed from canine myocardial infarction, although small changes were observed in some tissues exhibiting slow channel action potentials. These experiments show that amrinone did not influence either Na+-dependent inward currents or Na+-K+ exchange mechanisms. Instead, amrinone facilitated slow channel action potentials in cardiac tissue and thereby could alter cardiac contractility, as well as conduction within reentry circuits in hearts which possess appropriate pathophysiologic substrates.