缬沙坦对家兔急性心肌梗死后左心室心肌电生理的影响

Effects of valsartan on the electrophysiology of left ventricular myocytes after myocardial infarction in rabbits

目的探讨血管紧张素II的1型受体拮抗剂缬沙坦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、心肌梗死组和缬沙坦组。3组均在无菌条件下开胸，其中心肌梗死组和缬沙坦组分别结扎左冠状动脉前降支。缬沙坦组术后第2天给予缬沙坦（10mg·kg^1·d^-1），3组均喂养12周。3组家兔分别在心肌梗死前、心肌梗死后5min及12周记录左心室内、中、外膜层单向动作电位时限（MAPD），并记录心肌梗死后12周诱发的恶性心律失常，及采用全细胞膜片钳技术记录短暂外向钾电流（Ito）的变化。结果心肌梗死组和缬沙坦组在心肌梗死后5min3层左心室肌APD90较心肌梗死前明显延长。心肌梗死后12周，心肌梗死组3层左心室肌APD90较心肌梗死前仍明显延长（P〈0．05），但缬沙坦组3层心室肌APD90与心肌梗死前相比差异无统计学意义（P〉0．05）；且心肌梗死组跨室壁复极离散度（TDR）较假手术组、缬沙坦组明显延长（P〈0．05），缬沙坦组与假手术组之间TDR比较差异无统计学意义（P〉0．05）。缬沙坦组明显降低心肌梗死后室性心动过速／心室颤动的发生率（缬沙坦组与心肌梗死组相比：15％对60％，P〈0．05）。假手术组、心肌梗死组和缬沙坦组，Ito电流密度分别为（8．56±0．72）pA／pF、（4．51±0．48）pA／pF和（7．24±0．68）pA／pF，心肌梗死组显著低于假手术组及缬沙坦组（P〈0．05）；缬沙坦组与假手术组比较差异无统计学意义（P〉0．05）。结论缬沙坦明显降低家兔心肌梗死后恶性室性心律失常的发生率，其机制可能与抑制家兔心肌梗死后电重构有关。

Objective The purpose of this study was to investigate whether specific angiotensin II type t receptor blockade with valsartan would affect arrhythmia generation in rabbits with myocardial iIffarction and discuss the mechanism of its antiarrhymic efficacy. Methods Twenty-four rabbits were divided into 3 groups： sham-operated （ SHAM ） group （ n = 8 ）, myocardial infraction （MI） group （ n = 8 ） and valsartan （VAL） group （ n = 8 ）. SHAM group received a median sternotomy without left ventricular coronary artery ligation. MI and VAL groups rabbits received a median sternotomy followed by left coronary artery ligation. After MI, VAL group rabbits were fed with valsartan （ 10 mg ·kg^-1 · d^-1 ） for 12 weeks. Myoeytes were isolated from the border zone of infracted left ventricular wall. Monophasic action potential duration was recorded by a multichannel physiograph and potassium current was recorded using whole-cell patch clamp technique. Results The action potential duration of repolarization 90% （APD90） of three-tier ventrieular myoeytes was prolonged after MI 5 min. Furthermore, in MI group ,the APD90 was prolonged than that before MI after MI 12w. However, in VAL group ,there was significant difference between before and after MI 12w. The transmural dispersion of repolarization （TDR） was increased after MI. The increase of TDR was reversed by valsartan. The incidence of ventricular tachycardia/fibrillation （VT/VF） was markedly decreased in VAL group than in MI group. The density of ho was lower in MI group than in SHAM and VAL groups [ （4.51±0. 48 ） pA/pF ,8.56 ±0. 72 ） pA/pF and （7.24±0. 68） pA/pF]. Conclusions Valsartan reduced the electrophysiologic heterogeneities and the VT/ VF in rabbits with myocardial infarction. This effect of valsartan may contribute to its antiarrhythmic efficacy.