胺碘酮对大鼠肥厚心肌细胞急性电生理作用的研究

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。

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

OBJECTIVE: The aim of the present study was to investigate the acute action of amiodarone (AM) on the inward currents I(Na), I(Ca-L) and outward currents I(k), I(k1), I(to) 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 micromol/L AM and whole cell patch clamp technique was used to study the acute effects of AM on the inward currents I(Na), I(Ca-L) and outward currents I(k), I(k1), I(to). RESULTS: (1) Compared with the normal ventricular myocytes, the current density of I(k), I(ks), I(to) and I(k1) were all decreased in hypertrophied myocytes, but I(Na) and I(Ca-L) remained unchanged. (2) I(Ca-L) was blocked by 59.0% +/- 4.4% in normal myocytes but only blocked by 16.7% +/- 8.0% in hypertrophied myocytes after 50 micromol/L AM application; IC(50) of I(Na) were 9.2 micromol/L and 5.9 micromol/L in normal and in hypertrophied myocytes, respectively; I(to) was blocked by 55.9% +/- 5.5% in normal myocytes and 23.0% +/- 2.8% in hypertrophied myocytes after 50 micromol/L AM application. I(k1) was not affected by AM in both normal and hypertrophied myocytes; I(ks) was blocked by 21.6% +/- 5.6% in normal myocytes and 42.7% +/- 9.2% in hypertrophied myocytes after 10 micromol/L AM application. CONCLUSION: Our results show that the sensitivity of hypertrophied myocytes to AM on I(Na), I(ks) were higher than that of normal myocytes, while the sensitivity on I(Ca-L), I(k1), I(to) were lower than that of normal myocytes favoring the use of AM on hypertrophied myocardium for antiarrythmic therapy.