ＫＷ‐３０４９（新規Ｄｉｈｙｄｒｏｐｙｒｉｄｉｎｅ‐ｔｙｐｅＣａきっ抗剤）の心臓に対する電気生理学的作用

Abstract

Effects of KW-3049 on electrophysiological properties of the heart were examined using Langendorff-perfused hearts and superfused sinus nodal tissues of rabbits and superfused guinea-pig ventricular muscles. In rabbit hearts, KW-3049 at concentrations above 10(-7) M caused a dose-related prolongation of atrio-His bundle conduction time (AH), whereas His bundle-ventricular conduction time (HV) was unaffected. In spontaneously firing rabbit sinus nodal tissues, KW-3049 at concentrations above 10(-8) M prolonged cycle length significantly. At 10(-6) M, amplitude and the maximum upstroke velocity of sinus nodal action potential were decreased as well. In normally polarized guinea-pig ventricular muscles under 4 mM [K+]0, KW-3049 at concentrations above 10(-6) M shortened the action potential duration without affecting the resting membrane potential and the maximum upstroke velocity of action potential (Vmax). The Vmax of slow action potentials induced by isoproterenol at 10(-7) M was inhibited significantly by additional application of KW-3049 at concentrations above 10(-9) M. At above 10(-8) M, the amplitude and duration of slow action potentials were reduced significantly. The potency of this slow action potential inhibition by KW-3049 was slightly less than that of nifedipine, while it was 10 to 100 times greater than that of verapamil. Spontaneous activity of ventricular muscles induced by BaCl2 at 1 mM was abolished completely at 16 min after application of KW-3049 at 10(-7) M. These results suggest that KW-3049 may have a potent and selective inhibitory action on cardiac slow calcium channels.