卡维地洛对陈旧性心肌梗死大鼠离体心脏单相动作电位和心室不应期的影响

Effect of carvedilol on monophasic action potential and refractory period of isolated heart in rats with healed myocardial infarction

目的观察陈旧性心肌梗死（HMI）大鼠离体心脏单相动作电位（MAP）及心室有效不应期（ERP）的变化及卡维地洛对其影响。方法制作大鼠MI模型，术后24h存活大鼠24只随机分为卡维地洛组（Car组）和HMI组，分别给予卡维地洛（10mg·kg^-1·d^-1）及安慰剂。另行假手术为对照组（n=10），只穿线不结扎。HMI组和假手术组大鼠给予等量蒸馏水灌胃。8周后行血流动力学测定；Langendorff离体心脏灌流，记录大鼠左心室前壁梗死边缘区（IBZ）的MAP，测量动作电位振幅（APA及20％、50％和90％MAP复极时程（MAPD20、MAPD50和MAPD90）；测定心室ERP。数据用均数±标准差（x^-±s）表示，统计分析采用单因素方差分析，组间比较采用SNK法，以P〈0．05为差异具有统计学意义。结果与假手术组（5．02±1．92）mmHg相比，HMI组左室舒张末压（LVEDP）（29．66±5．57）mmHg显著增加，左室内压最大收缩和舒张速率（±dp／dmax）显著降低；MAPD20（17．2±3．8）ms、MAPD50（43．7±7．8）ms、MAPD50（94．8±7．9）ms及ERP（75．6±10．7）ms均明显延长，APA（3．75±0．70）mV下降。给予卡维地洛后，与HMI组相比，LVEDP显著降低，±dp／dtmax显著升高；MAPD20、MAPD50、MAPD50及ERP均较HMI组缩短，APA较HMI组增加。Vmax在各组差异无显著性。结论卡维地洛能改善大鼠MI后的血流动力学变化，抑制MI后MAP20、MAPD50、MAPD50及ERP延长，可能是其防治恶性室性心律失常的机制。

Objective To investigate the changes of monophasic action potential and refractory period and the effect of carvedilol on them of isolated hearts in rats with healed myocardial infarction （HMI）. Method MI models were induced by ligating left anterior descending coronary branch. After 24 hours, 24 survival rats were randomly divided into carvedilol group （Car group） and HMI group. Rats in the sham group had left thoracotomy but without coronary artery ligation. Car group were administrated with carvedilol 10 mg· kg^- 1· d^- 1 HMI and sham group were administrated with the same doses of distilled water. Eight weeks after therapy, hemodynamics were measured by inserting catheters. After that, hearts were isolated and perfused by Langendorff instrument. With the monophasic action potential （MAP） recording technique, the MAP of infarction border zone （IBZ） in the anterior left ventricular wall of rat hearts were recorded. Action potential amplitude （APA）, MAP duration （MAPD） at 20%, 50% and 90% repolarization （MAPD2o, MAPDso and MAPDgo）, effective refractory periods （ERP） were measured. Data were expressed as mean ± SE （x^-± s）. One-way analysis of variance was used for comparison among groups, and SNK test for comparison between two groups. Statistical significance was set at P 〈0.05. Results The left ventricle end diastolie pressure （LVEDP） in HMI group [ （29.66± 5.57） mmHg] was inereased signifieanfly eompared with those in sham group[（5.02±1.92） mmHg], maximal late of systolie and diastolie （±dp/dmax） of LV pressure decreased signifieanfly. MAPD20 [（17.2±3.8） ms], MAPD50 [ （43.7 ± 7.8） ms], MAPD50[ （94.8±7.9） ms] and ERP ] （75.6± 10.7） ms] inereased signifieanfly in the HMI group eompared with the sham group, while APA [ （3.75 ± 0.70） my] deereased signitieantly. In comparison with the HMI group, the LVEDP decreased significantly, ± dp/dtmax increased signifieantly in earvedilol group. At the same time, MAPD20, MAPD20, MAPD50 and ERP decreased signifieantly and APA inereased signifieantly in earvedilol group. While there were no differenees of Vmax in eaeh group. Conclusions Carvedilol eould improve not only hemodynamies in rats＇ hearts with HMI, but also shorten the abnormal prolongation of MAPD and effeedve refraetory period. These may he the mechanisms of earvedilol in preventing arrhythmia in HMI.