Shibuya N, Hatakeyama N, Yamazaki M, Masuda A, Ito Y, Momose Y
Department of Anesthesiology, Faculty of Medicine, Toyama Medical and Pharmaceutical University.
Masui. 1993 Sep;42(9):1306-12.
We studied the effects of bupivacaine on the contractility and membrane potentials in isolated dog papillary muscle. Bupivacaine (10(-6)-10(-4) M) produced dose-dependent depression of twitch tension elicited by electrical stimulation. These inhibitory effects were greater at high frequencies of stimulation (2, 3 Hz) than at low frequencies (less than 1 Hz). Bupivacaine did not alter the resting membrane potential, but produced a reduction in Vmax of the action potentials, in a dose-dependent and reversible manner (concentrations from 10(-6) to 10(-4) M). Bupivacaine 10(-4) M often blocked the fast action potentials in normal Tyrode's solution. In high K+ (26 mM) Tyrode's solution, bupivacaine inhibited both slow action potentials and associated contractions in the presence of isoproterenol. These results suggest that low concentrations of bupivacaine decreases the contraction mainly due to Na+ channel block, whereas at higher concentration, this anesthetic may block Ca2+ channels. In addition, isoproterenol may be clinically effective in the treatment of bupivacaine cardiotoxicity due to stimulation of Ca2+ mediated slow action potentials through beta-receptors.
我们研究了布比卡因对离体犬乳头肌收缩性和膜电位的影响。布比卡因（10⁻⁶ - 10⁻⁴ M）对电刺激诱发的抽搐张力产生剂量依赖性抑制。这些抑制作用在高频刺激（2, 3 Hz）时比低频刺激（小于1 Hz）时更强。布比卡因不改变静息膜电位，但以剂量依赖性和可逆方式（浓度范围为10⁻⁶至10⁻⁴ M）降低动作电位的最大上升速率（Vmax）。10⁻⁴ M的布比卡因在正常台氏液中常阻断快速动作电位。在高钾（26 mM）台氏液中，布比卡因在异丙肾上腺素存在的情况下抑制慢动作电位及相关收缩。这些结果表明，低浓度布比卡因主要通过阻断钠通道降低收缩，而在较高浓度时，这种麻醉药可能阻断钙通道。此外，异丙肾上腺素可能通过β受体刺激钙介导的慢动作电位，在临床上对布比卡因心脏毒性的治疗有效。
