胺碘酮对左室肥厚家兔跨室壁Cx43异质性的影响

Effects of amiodarone on transmural heterogeneous of Cx43 in rabbits with left ventricular hypertrophy

目的观察胺碘酮片剂对左室肥厚(LVH)家兔三层心肌间Cx43表达的差异,探讨LVH恶性室性心律失常(MVA)的机制及处理措施。方法将20只家兔按随机数字法分成胺碘酮治疗组和LVH对照组,每组各10只。两组家兔均采用传统的腹主动脉缩窄术后继续喂养8周以制备LVH模型。治疗组手术后给予经口喂服盐酸胺碘酮片,每日50 mg/kg,连续4周,然后继续喂养4周并进行实验;对照组喂养生理盐水8周后进行实验。分别检测两组家兔心外膜下、中层心肌和心内膜下心肌细胞的单相动作电位复极90%时程(APD90)、跨室壁复极离散度(TDR)以及左心室三层心肌Cx43蛋白表达的差异。结果 (1)治疗组家兔心内、外膜下、中层心肌的APD90分别为(275.30±11.42)ms、(251.50±10.98)ms和(295.40±12.41)ms,均较LVH对照组的(236.30±16.51)ms、(217.69±14.25)ms和(265.12±20.01)ms显著延长,差异具有显著统计学意义(P<0.01),但是治疗组的TDR为(38.96±10.91),明显小于对照组的(48.56±11.23),差异有统计学意义(P<0.05)。(2)治疗组家兔三层心肌的Cx43蛋白表达分别为(0.60±0.07)、(0.48±0.05)和(0.57±0.06),均较对照组的(0.53±0.04)、(0.31±0.06)和(0.48±0.04)明显提高(P<0.05),但以中层心肌的增加更为明显,从而缩小了三层心肌间Cx43蛋白表达的差异,△Cx43减少[(0.14±0.06)vs(0.23±0.08),P<0.01]。结论胺碘酮能改善左室肥厚的跨室壁Cx43表达异质性,缩小左心室心肌跨室壁复极不均一性,这可能是其减少MVA发作的生理机制。

Objective To observe the effects of feeding amiodarone on heterogeneity of Cx43 expression in the rabbit model with left ventricular hypertrophy(LVH), and investigate the mechanisms of amiodarone on malignant ventricular arrhythmias(MVA) induced by LVH. Methods Twenty rabbits were randomly divided into LVH group(n=10) and amiodarone group(n=10). LVH model was produced with traditional abdominal aortic coarctation in the both group. Rabbits in the LVH group were continuing to feed for 8 weeks after surgery, and given feeding amiodarone tablets [50 mg/(kg·d)] for four consecutive weeks after surgery in the amiodarone group. 90% monophasic action potential repolarization duration(APD90) of subepicardial, midmyocardial and subendocardial myocardium, transmural dispersion of repolarization(TDR) and Cx43 protein expression in three layers of myocardium were measured in both groups. Results(1) APD90 of endomyocardial, epimyocardial and midmyocardiallayers in the amiodarone group were(275.30 ± 11.42) ms,(251.50 ± 10.98) ms and(295.40 ± 12.41) ms respectively, which significantly prolonged than those in the LVH group of(236.30 ± 16.51) ms,(217.69 ± 14.25) ms and(265.12 ± 20.01) ms(P<0.01). However, TDR were significantly decreased in the amiodarone group [(38.96 ± 10.91) vs(48.56 ± 11.23), P<0.05].(2) Three myocardial Cx43 protein expression in the amiodarone group were(0.60±0.07),(0.48±0.05) and(0.57±0.06) respectively, which significantly increased compared to those in the LVH group [(0.53±0.04),(0.31±0.06) and(0.48±0.04)], P<0.05. Increasing of midmyocardial Cx43 was more significant, so difference of Cx43 among three myocardium reduced and △Cx43 decreased [(0.14±0.06) vs(0.23±0.08), P<0.01]. Conclusion Amiodarone can reduce MVA in LVH by decreasing ransmural heterogeneity of Cx43 protein expression and improving transmural dispersion of repolarization.