胺碘酮慢性作用对兔心室肌细胞L型钙通道电流和跨壁动作电位相关性研究  

Effects of chronic amiodarone therapy on L-type calcium current recovery and action potential duration of rabbit ventricular myocytes

作　　者：赵晓静[1] 郭东林 邬颖 刘腾先 严干新 

机构地区：[1]西安交通大学医学院第二附属医院急诊科,710004 [2]美国杰弗逊大学MLH心脏中心实验室

出　　处：《中华心血管病杂志》2009年第6期528-531,共4页Chinese Journal of Cardiology

摘　　要：目的从单个心室肌细胞L型钙通道电流时间常数（τ）和组织块跨壁动作电位复极90％时程（APD90），探讨胺碘酮慢性作用抗心律失常的可能细胞电生理机制。方法健康兔口服胺碘酮80mg·kg^-1·d^-1共4周，记录离体兔带血管心室肌组织块跨膜心室肌细胞动作电位后分离心室肌细胞，记录单细胞L型钙通道电流τ，比较对照组、胺碘酮组及索他洛尔组干预下τ与APD90比值（τ／APD90）变化。结果对照组τ为（98±8）ms（n=10）、APD90为（220±10）ms（n=5）、τ／APD90为0．44±0．03。与对照组相比，胺碘酮组τ明显延长[为（164±8）ms，n=8，P〈0．05]，APD90亦明显延长[为（321±12）ms，n=5，P〈0．05]，τ／APD90较对照组增加（分别为0．51±0．03与0．44±0．03，P〈0．05）。索他洛尔（3×10^-5mmol／L）组与对照组相比，τ明显延长[为（128±7）ms，n=8，P〈0．05]，但因APD90延长较著[为（405±13）ms，n=4，P〈0．01]，使τ／APD90较对照组明显减少（分别为0．32±0．05与0．44±0．03，P〈0．05）。索他洛尔＋胺碘酮组的τ为（150±12）ms、APD90为（355±11）ms（n=4），与索他洛尔组比较，τ／APD90增加（为0．44±0．02，P〈0．05），与对照组相比，差异无统计学意义（P〉0．05）。结论心室肌细胞膜L型钙通道电流的τ／APD90大小与胺碘酮慢性作用相关，这为胺碘酮慢性作用的安全性提供了一种可能解释。Objective To investigate the effects of chronic amiodarone therapy on L-type calcium current recovery and action potential duration of rabbit ventricular myocytes. Methods Healthy rabbits （ 1.6 - 1.8 kg） were treated with amiodarone （ 80 mg · kg^-1·d^-1 ） for four weeks. Action potential duration （APD） was recorded under isolated arterially perfused left ventricular wedge preparation, then single myocytes were isolated using enzyme digestion. L-type calcium current recovery （time constant, τ） were determined by fitting data with monoexponential. τ/APD90 were compared in cells treated with saline, amioderone and sotalol（3 × 10^-5 mmol/L）. Results In chronic amiodarone treated myocytes, τ[ （ 164 ± 8） ms vs. （98±8） ms,P〈0.05], APD90[（321±12）ms vs. （220±10） ms,P〈0.05] and τ/APD90 （0. 51 ± 0.03 vs. 0. 44 ± 0. 03, P 〈 0. 05 ） were significantly increased than those in control myocytes. Sotalol significantly increased τ[ （128±7） ms vs. （98±8）ms, P〈0. 05] and ADP90[ （405 ± 13）ms vs. （ 220 ± 10 ） ms, P 〈 0. 05 ] while reduced the τ/APD90 （ 0. 32 ± 0. 05 vs. 0. 44 ± 0. 03, P 〈 0. 05 ） compared to control myocytes. Condusion The differential effect of amiodarone and sotalol on ventricular myocytes τ/APD90 ratio might be responsible for the safety profile of these two drugs.

关 键 词：胺碘酮 钙通道 动作电位 

分 类 号：R686[医药卫生—骨科学]