胺碘酮对大鼠肥厚心肌细胞急性电生理作用的研究

The acute electrophysiological effects of amiodarone on normal and hypertrophied rat myocytes

目的研究胺碘酮对正常心肌与肥厚心肌细胞急性电生理作用的区别,探讨胺碘酮在病态心肌应用中的合理性。方法SPRAGUEDAWLAY(SD)大鼠缩窄腹主动脉,建立左心室肥厚模型。应用膜片钳技术,选用不同浓度胺碘酮灌流正常心肌细胞和肥厚心肌细胞,观察内向电流:钠流(INA)、L型钙流(ICAL)和外向电流:延迟整流性钾流(IK)、瞬间复极钾流(ITO)、内向整流性钾流(IK1)。以多非利特(DOFETILIDE)阻滞延迟整流性钾流的快速成分(IKR),所测IK代表延迟整流性钾流的缓慢成分(IKS)。结果(1)肥厚心肌细胞电重构特征为肥厚心肌INA、ICAL与正常心肌相近,但肥厚心肌的外向电流较正常心肌减小,表现在IK、IKS、ITO和IK1的电流密度降低。(2)胺碘酮50ΜMOL/L抑制正常心肌细胞(59.0±4.4)%的ICAL,对肥厚心肌ICAL的抑制不明显,仅抑制(16.7±8.0)%的ICAL;胺碘酮抑制正常心肌细胞和肥厚心肌细胞INA的半抑制浓度(IC50)分别为9.2ΜMOL/L和5.9ΜMOL/L;胺碘酮50ΜMOL/L阻滞正常心肌细胞和阻滞肥厚心肌细胞ITO分别为(55.9±5.5)%和(23.0±2.8)%;胺碘酮对正常心肌细胞或肥厚心肌细胞IK1的影响较小;胺碘酮对IKS阻滞程度,肥厚心肌大于正常心肌,胺碘酮10ΜMOL/L抑制正常心肌和肥厚心肌IKS分别为(21.6±5.6)%和(42.7±9.2)%。提示胺碘酮阻滞肥厚心肌细胞INA、IKS的敏感性大于正常心肌细胞,阻滞ICAL、ITO、IK1的敏感性又低于正常心肌细胞。结论胺碘酮对电重构的肥厚心肌细胞急性电生理反应,有利于其在抗心律失常中的应用。

Objective The aim of the present study was to investigate the acute action of amiodarone （AM） on the inward currents INa, Ica-L and outward currents Ik , Ik1, Ito in hypertrophied and normal rat ventricular myocytes. Methods The pressure overload hypertrophy rat model was established by partial ligation of ascending aorta for 4 weeks. Ventricular myocytes were exposed to 0, 01,0, 1,1,10 and 50 Ixmol/L AM and whole cell patch clamp technique was used to study the acute effects of AM on the inward currents INa/Ca-L and outward currents Ik , Ikl,Ito . Results （ 1 ） Compared with the normal ventficular myocytes, the current density of Ik ,lk, ,I,o and Ik1 were all decreased in hypertrophied myocytes, but IN, and Ica-L remained unchanged. （2） ICa-L was blocked by 59. 0% ±4. 4% in normal myocytes but only blocked by 16. 7% ± 8. 0% in hypertrophied myocytes after 50μmol/L AM application;IC5o of INa were 9. 2μmol/L and 5.9 μmol/L in normal and in hypertrophied myocytes, respectively;Ito was blocked by 55.9% ± 5. 5% in normal myocytes and 23.0% ± 2.8% in hypertrophied myocytes after 50 μmol/L AM application. Ik1 was not affected by AM in both normal and hypertrophied myocytes;Ik, was blocked by 21.6% ± 5. 6% in normal myocytes and 42. 7% ± 9. 2% in hypertrophied myocytes after 10μmol/L AM application. Conclusion Our results show that the sensitivity of hypertrophied myocytes to AM on INa、Iks. were higher than that of normal myocytes, while the sensitivity on/Ca-L Ik1、Ito were lower than that of normal myocytes favoring the use of AM on hypertrophied myocardium for antiarrythmic therapy.