胺碘酮及其代谢产物去乙基胺碘酮对离体心肌电生理特性的影响。
Effects of amiodarone and its metabolite, desethylamiodarone, on the electrophysiologic properties of isolated cardiac muscle.
作者信息
Yabek S M, Kato R, Singh B N
出版信息
J Cardiovasc Pharmacol. 1986 Jan-Feb;8(1):197-207. doi: 10.1097/00005344-198601000-00029.
The electrophysiologic (EP) effects of chronically administered amiodarone (AM) is known, but the nature of its acute effects are unclear. Whether the delayed onset of AM action is due to its metabolite, desethylamiodarone (DAM), is also uncertain. By standard microelectrode techniques in isolated canine ventricular muscle (VM) and Purkinje fibers (PF) and in rabbit sinoatrial (SA) node and atrium, we therefore studied the comparative effects of AM and DAM, 10(-6) M (0.68 micrograms/ml), 10(-5) M (6.8 micrograms/ml), and 5 X 10(-5) M (34 micrograms/ml), dissolved in ethanol and homologous serum. In VM, PF, and atria stimulated at 1 Hz, AM and DAM had no effect on Vmax, action potential amplitude (APA), or resting membrane potential. At 2-4 Hz, AM exerted a marked use-dependent effect in VM and PF. In atria, 5 X 10(-5) M, AM and DAM increased (p less than 0.01) action potential duration at 90% repolarization (APD90); the effective refractory period (ERP) increased by 10.5% (p less than 0.05 for AM) and 21.6% (p less than 0.01 for DAM). In VM, AM increased APD90 by 9.6% (p less than 0.01) at 10(-6) M, 13.7% (p less than 0.01) at 10(-5) M, and 16.9% (p less than 0.01) at 5 X 10(-5) M. The corresponding values for DAM were 5.6% (NS), and 7.3% (p less than 0.01), respectively. The ERP in VM was increased significantly by AM but not by DAM at all 3 drug concentrations without a change in APD90/ERP ratio. In PF, AM and DAM decreased APD50 and APD90; the effects were greater than those produced by the superfusion medium, but the degree of shortening in ERP induced by AM and DAM was not. AM and DAM (10(-5) and 5 X 10(-5) M) increased spontaneous cycle length of rabbit SA node. AM significantly decreased slope of phase 4 depolarization (10.4% at 10(-6) M, p less than 0.05; 14.5% at 10(-5) M, p less than 0.01; 24.0% at 5 X 10(-5) M, p less than 0.01). At 5 X 10(-5) M, AM significantly decreased APA, maximum diastolic potential and threshold potential with an insignificant effect on APD100.(ABSTRACT TRUNCATED AT 400 WORDS)
长期服用胺碘酮（AM）的电生理（EP）效应是已知的，但其急性效应的本质尚不清楚。AM作用延迟起效是否归因于其代谢产物去乙基胺碘酮（DAM）也不确定。因此，我们采用标准微电极技术，在离体犬心室肌（VM）和浦肯野纤维（PF）以及兔窦房结（SA）和心房中，研究了溶解于乙醇和同源血清中的AM和DAM在10⁻⁶M（0.68微克/毫升）、10⁻⁵M（6.8微克/毫升）和5×10⁻⁵M（34微克/毫升）浓度下的比较效应。在以1Hz刺激的VM、PF和心房中，AM和DAM对最大上升速率（Vmax）、动作电位幅度（APA）或静息膜电位均无影响。在2 - 4Hz时，AM在VM和PF中表现出明显的频率依赖性效应。在心房中，5×10⁻⁵M的AM和DAM使90%复极化时的动作电位时程（APD90）增加（p<0.01）；有效不应期（ERP）分别增加10.5%（AM，p<0.05）和21.6%（DAM，p<0.01）。在VM中，10⁻⁶M的AM使APD90增加9.6%（p<0.01），10⁻⁵M时增加13.7%（p<0.01），5×10⁻⁵M时增加16.9%（p<0.01）。DAM的相应值分别为5.6%（无显著性差异）和7.3%（p<0.01）。在所有3种药物浓度下，VM中的ERP均显著增加，而DAM则无此作用，且APD90/ERP比值无变化。在PF中，AM和DAM使APD50和APD90缩短；其效应大于灌流液所致，但AM和DAM诱导的ERP缩短程度并非如此。AM和DAM（10⁻⁵和5×10⁻⁵M）增加了兔SA结的自发周期长度。AM显著降低4期去极化斜率（10⁻⁶M时为10.4%，p<0.05；10⁻⁵M时为14.5%，p<0.01；5×10⁻⁵M时为24.0%，p<0.01）。在5×10⁻⁵M时，AM显著降低APA、最大舒张电位和阈电位，而对APD100影响不显著。（摘要截于400字）
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