胺碘酮急性和慢性给药对正常和肥厚心肌电生理作用的差别

The difference of electrophysiological effects during acute and chronic administration of amiodarone between normal and hypertrophic myocytes

目的研究胺碘酮对肥厚心肌与正常心肌急性和慢性电生理作用的差别。方法采用缩窄腹主动脉的SD大鼠为实验模型,4周后形成左室肥厚,应用酶解技术获得单个心室肌细胞;应用膜片钳技术检测内向电流INa、ICa-L和外向电流Ik、Ito、Ik1,应用多非利特阻滞Ikr,所测Ik代表Iks;急性实验采用不同浓度胺碘酮灌流心肌细胞,慢性试验采用胺碘酮100mg·kg-1·d-1灌胃4周。结果肥厚心肌细胞电重构特征为Ito、Ik、Iks、Ik1外向电流密度降低;胺碘酮对肥厚心肌急性电生理作用为INa、Iks阻滞强度大于正常心肌,但ICa-L阻滞弱于正常心肌;胺碘酮的慢性作用,正常心肌与肥厚心肌相似,表现Ito、Ik、Iks阻滞,对内向电流影响较小。结论胺碘酮对肥厚心肌细胞的急性和慢性电生理作用,均提示其有利于肥厚心肌的抗心律失常治疗。

Objective To compare the differences of amiodarone＇s （AM） electrophysiological effects between hypertrophic and normal ventricular myocytes, and then to investigate the rational antiarrythmic usage of AM on pathosis myocytes. Mehtods The pressure overload hypertrophy models of rats were established by partial ligation of ascending aorta for 4 weeks. To observe the short-term effects of amiodarone, cells were exposed acutely to 0.01, 0. 1, 1, 10, 50 μmol/L amidarone respectively. To observe the long-term effects of amiodarone, the hypertrophic and normal rats were administered by oral amiodarone （ 100 mg· kg^- 1· d^ -1 ） for 4 weeks before cell isolation. Whole cell patch-clamp techniques were used to study the acute and chronic effects of amiodarone on the inward currents ⅠNa, ⅠCa-L and outward currents Ⅰk , Ⅰk1 , Ⅰto in rat single ventricular myocytes isolated from normal and pressure overload rats. Then the current changes between before and after AM irrigation on a single cell and its differences between hypertrophic and normal group were compared. Results The electroreconstruction of hypertrophic myocytes mainly exhibited outward currents were decreased. The sensitivities of amiodarone＇s action on ⅠNa ,Ⅰks were higher than control, while the sensitivities on ⅠCa-L ,Ⅰk1 ,Ⅰto were lower than control. The chronic effects of AM were similar between normal and hypertrophic myocytes, but the chronic effects were different from the acute effects, which demostrated that the chronic action had little effects on inward currents, but mainly inhibited outward currents. Conclusion The electrophysiological effects of AM on hypertrophic heart are more fit for antiarrythmias therapy.