雷米普利对兔心肌梗死后心室肌电生理的影响

Effects of Ramipril on Electrophysiology of Ventricular Myocytes After Myocardial Infarction in Rabbits

目的:探讨血管紧张素转化酶抑制剂雷米普利对兔心肌梗死后室性心律失常发生的影响及其可能机制。方法:24只家兔随机分为假手术组(SHAM)、心肌梗死组(MI)和雷米普利组(RAM)。3组均在无菌条件下开胸,其中心肌梗死组和雷米普利组分别结扎左冠状动脉前降支。雷米普利组术后第2天给予雷米普利[1mg/(kg.d)],3组共喂养12周。3组家兔分别在心肌梗死前、心肌梗死后12周记录左心室内、中、外膜层单相动作电位(MAP),并记录心肌梗死后12周诱发的恶性心律失常次数,及采用全细胞膜片钳技术记录L-型钙通道电流(Ica-L)的变化。结果:①RAM组明显降低心肌梗死后室性心动过速、心室颤动(VT/VF)的发生次数(2.6±0.8比12.4±2.9,P<0.05)。②心肌梗死后12周,MI组3层左心室肌APD90较心肌梗死前明显延长(258.2±21.1比230.1±23.2,278.0±23.8比245.8±25.4,242.6±22.7比227.0±21.7,P<0.05);RAM组3层心室肌APD90与心肌梗死前相比没有明显差异。而且,MI组跨壁复极离散度(TDR)较SHAM、RAM组明显延长(分别为36.2±10.2,18.7±6.2,24.9±8.7,P<0.05);RAM与SHAM组之间TDR比较无显著性差异。③假手术组、心肌梗死组和缬沙坦组Ica-L电流密度分别为(-6.29±0.65)pA/pF、(-9.12±0.73)pA/pF和(-7.05±0.68)pA/pF,心肌梗死组显著低于假手术组及雷米普利组(P<0.05);雷米普利组与假手术组比较无统计学差异。结论:雷米普利明显降低家兔心肌梗死后恶性室性心律失常的发生次数,其机制可能与抑制家兔心肌梗死后电重构有关。

Objective：To determine whether specific angiotensin-conventing enzyme inhibitor with ramipril would affect arrhythmia generation in rabbits after myocardial infarction（MI）,and to study the mechanism of its antiarrhythmic efficacy.Methods：Twenty-four rabbits were divided into three groups：sham-operated（SHAM） group（n=8）,MI group（n=8） and ramipril（RAM） group（n=8）.SHAM group rabbits received a median sternotomy without left ventricular coronary artery ligation.MI and RAM groups received a median sternotomy followed by left coronary artery ligation.After MI,RAM group rabbits were fed with ramipril（1 mg/kg per day） for 12 weeks.Ventricular tachycardia or fibrillation（VT/VF） episodes and monophasic action potential were recorded by a multichannel physiograph.L-type Ca2＋ current was recorded using whole-cell patch clamp technique.Results：VT/VF episodes were markedly decreased in RAM group than that in MI group after 12 weeks（2.6±0.8 vs 12.4±2.9,P0.05）.Twelve weeks after MI,the action potential duration of repolarization 90%（APD90） of three-tier ventricular myocytes in MI group was prolonged than that before MI（258.2±21.1 vs 230.1±23.2,278.0±23.8 vs 245.8±25.4,and 242.6±22.7 vs 227.0±21.7,respectively,all P0.05）;however,the APD90 had no changes 12 weeks after MI both in RAM and SHAM groups（P0.05）.The transmural dispersion of repolarization（TDR） was increased after MI,and the increase of TDR was reversed by ramipril（36.2±10.2,18.7±6.2,and 24.9±8.7 respectively in MI,RAM,and SHAM groups,P0.05）.The density of Ica-L was lower in MI group than in SHAM and RAM groups.Conclusion：Ramipril reduced the VT/VF episodes and the electrophysiologic heterogeneities in rabbits with myocardial infarction.This ability of ramipril may have relationship with inhibited electrical remodeling after MI.