Hemodynamic and electrocardiographic actions of the new intracellular calcium antagonist, KT-362, in the conscious dog

Effects of the intracellular calcium antagonist, KT-362, on systemic and coronary hemodynamics and the electrocardiogram were evaluated in chronically instrumented, awake dogs during intravenous infusion or bolus administration. Both methods of administration resulted in systemic hypotension, tachycardia and decreases in left ventricular pressure and peak positive left ventricular dP/dt. KT-362 produced a transient increase in mean coronary blood flow velocity only during bolus injection, while subendocardial segment shortening was depressed only by drug infusion. Prolongation of QRS duration and the QT interval (corrected for change in heart rate, QTc) also occurred during drug infusion. The results suggest that the hemodynamic effects of intracellular calcium antagonism by KT-362 are qualitatively similar to those of other calcium channel blocking agents which inhibit extracellular calcium influx. In contrast, the actions of KT-362 on cardiac conduction may be different from those of other slow channel calcium blocking agents.