Electrophysiologic effects of a novel Ca antagonist, SA2572, in isolated rabbit and guinea pig hearts.

Cardiac effects of SA2572, a newly synthesized Ca antagonist, were evaluated in guinea pig and rabbit hearts with electrophysiologic technique. SA2572(10(-6)-10(-5) M) decreased the upstroke velocity (Vmax) and the duration of the action potential (APD30) in guinea pig papillary muscles in a concentration- and frequency-dependent manner without affecting the resting potential. The slow responses (high K+ + isoproterenol) were suppressed by SA2572 at 10(-6) M. In rabbit sinus node, SA2572(10(-7)-5 x 10(-6) M) caused a concentration-dependent decrease in the amplitude and Vmax of the action potential and tended to prolong the spontaneous cycle length. In Langendorff-perfused rabbit hearts electrically driven at 2 Hz, SA2572(5 x 10(-8)-10(-6) M) produced concentration-dependent prolongations of the atrio-His bundle conduction time (A-H interval) and the His bundle-ventricular conduction time (H-V interval) concomitantly with a reduction of the developed tension of the ventricular muscle. These effects of SA2572 on the A-H and H-V intervals were more pronounced at higher stimulation frequency. Enantiospecificity was observed in these actions of SA2572, (-)-isomer of SA2572 having more potent inhibitory effects on slow channel-dependent than on fast channel-dependent phenomena. These results indicate that SA2572 has characteristics of both slow and fast channel blockers, and that these inhibitory effects are frequency dependent.