Nakaya H, Kimura S, Nakao Y, Kanno M
Eur J Pharmacol. 1984 Sep 17;104(3-4):335-44. doi: 10.1016/0014-2999(84)90410-2.
The electrophysiological effects of K-351 (0.3-300 microM), a new beta-adrenoceptor blocking drug, on canine Purkinje and ventricular muscle fibers were examined and compared with those of propranolol (0.3-30 microM) and sotalol (3-300 microM) using standard microelectrode techniques. K-351 and propranolol dose dependently reduced the maximum upstroke velocity of phase 0 and action potential amplitude in both cardiac tissues. Action potential durations (APD) of Purkinje fibers were shortened by both propranolol and K-351 but prolonged by sotalol. However, in ventricular muscle fibers K-351 and sotalol significantly prolonged APD and effective refractory periods which contrasted with the unchanged APD after propranolol. These results suggest that K-351 is a beta-blocking drug possessing a membrane stabilizing action (class I antiarrhythmic properties) and in ventricular muscles it can also exert an APD-prolonging effect (class III antiarrhythmic properties).
使用标准微电极技术,研究了新型β-肾上腺素受体阻断药物K-351(0.3 - 300微摩尔)对犬浦肯野纤维和心室肌纤维的电生理效应,并与普萘洛尔(0.3 - 30微摩尔)和索他洛尔(3 - 300微摩尔)进行了比较。K-351和普萘洛尔均剂量依赖性地降低了两种心脏组织中0期的最大上升速度和动作电位幅度。普萘洛尔和K-351均缩短了浦肯野纤维的动作电位持续时间(APD),但索他洛尔使其延长。然而,在心室肌纤维中,K-351和索他洛尔显著延长了APD和有效不应期,这与普萘洛尔作用后APD不变形成对比。这些结果表明,K-351是一种具有膜稳定作用(I类抗心律失常特性)的β阻断药物,在心室肌中它还可发挥延长APD的作用(III类抗心律失常特性)。