Electrophysiologic Effects of a Novel Ca Antagonist, SA2572, in Isolated Rabbit and Guinea Pig Hearts

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Abstract
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 (.ovrhdot.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+ + isoporterenol) were suppressed by SA2572 at 10-6 M. In rabbit sinus node, SA2572(10-7-5 .times. 10-6 M) caused a concentration-dependent decrease in the amplitude and .ovrhdot.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 .times. 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.