Interaction of BAY K-8644 with effects of digoxin in the dog heart-lung preparation

Abstract

Concentration-dependent effects of BAY K-8644, a dihydropyridine calcium channel agonist, on heart rate (HR), left atrial pressure (LAP) and maximal rate of left intraventricular pressure rise (+dP/dt max) were compared with those of isoproterenol and digoxin in dog heart-lung preparations during exposure to 0.8 vol% halothane. All there agents reduced LAP to nearly equal levels at maximally effective concentrations. Maximal increases in +dP/dt max induced by BAY k-8644 and digoxin were of similar magnitude (35 and 31%, respectively), and both agents increased HR slightly. Isoproterenol elevated both +dp/dt max and HR more than twice as much as the other agents. At a concentration which produced only small changes by itself, BAY K-8644 markedly increased the effects of digoxin on LAP and +dP/dt max. Furthermore, the same concentration of BAY K-8644 significantly reduced toxic effects of digoxin (arrhythmogenesis, elevation of LAP, reduction in systemic output). These data indicate that in the isolated blood-perfused heart digoxin's positive inotropic action may be enhanced by an appropriate concentration of BAY K-8644, while adverse effects are diminished.