Cardiac electrophysiologic effects of AHR 5360C

We used microelectrode and blood superfusion techniques to study the cardiac electrophysiologic effects of a new drug, AHR 5360C, which has antihypertensive and calcium channel blocking properties in several experimental models. AHR 5360C, 10(-7) M significantly depressed the amplitude of the slow response action potential in canine Purkinje fibers. The fast response action potential was also depressed in a dose-dependent fashion, but with a threshold concentration of 5 X 10(-6) M. AHR 5360C decreased normal automaticity and barium-induced abnormal automaticity at concentrations of 5 X 10(-6) and 10(-5) M respectively, as well as ouabain-induced delayed afterdepolarizations at a threshold concentration of 10(-6) M. In blood superfusion studies; i.v. administration of AHR 5360C, 0.3 mg/kg, significantly reduced blood pressure. Doses of 1.0 mg/kg induced a high degree of A-V block, further reduction of blood pressure, and no physiological changes in heart rate and in the blood superfused fibers. In conclusion, AHR 5360C has calcium blocking properties that depress A-V conduction at concentrations that do not affect the sodium-dependent fast response action potential.