β2肾上腺素受体在心肌梗死大鼠离体心脏机械电反馈中的作用及机制

目的观察β2肾上腺素受体在心肌梗死（MI）大鼠离体心脏机械电反馈中的作用，并探讨其可能机制。方法制作大鼠MI模型，同时设立假手术组。8周后行Langendorff离体心脏灌流，自制球囊牵张左心室。记录左心室前壁单相动作电位（MAP），测量MAP时程（MAPD）、50％和90％MAP复极时程（MAPD50、MAPD50），计算牵张诱发心律失常（SIA）的发生率。分别给予选择性β2受体阻滞剂ICI118．551及Gi蛋白抑制剂百日咳毒素（PTX），观察牵张前后、给药前后各指标的变化。结果与假手术组相比，MI后MAPD、MAPD50、MAPD50分别延长15．2％，46．5％和25．4％（P〈0．01）。牵张后，假手术组MAPD、MAPD50、MAPD50分别缩短12．4％、18．0％和16．5％（P〈0．01），MI对照组分别缩短26．0％、53．1％和24．0％（P〈0．01），较假手术组显著。MI组SIA发生率较假手术组明显升高（分别为22．4％，10．3％；P〈0．05）。应用ICI118．551、PTX后，牵张对MAPD、MAPD50、MAPD50的影响明显下降，差异无统计学意义，SIA发生率下降（由22．44％分别下降至8．83％、12．2％；P〈0．01）。结论牵张可使MAPD、MAPD50、MAPD50缩短，且MI组更敏感。ICI118．551、PTX可抑制牵张引起的电生理改变，β2肾上腺素受体参与MI后的心脏机械电反馈过程可能与Gi蛋白有关。

The role and mechanism of β2-adrenoceptor in mechanoelectric feedback of isolated rat heart after myocardial infarction

Objective To investigate the role of β2- adrenoceptor in mechanoelectric feedback and its mechanism in isolated rat heart after myocardial infarction（MI）. Methods MI models were formed by ligating coronary artery. After 8 weeks, the hearts were isolated and perfused with Langendorff equipment. Balloon inflation of the left ventricle of isolated heart was performed to increase the left ventricular preload and dilate the left ventricle. With the monophasic action potential（MAP） recording technique , the MAP of the anterior left ventricular wall of rat hearts was recorded. MAP durations（MAPD） at 50% and 90% （MAPD50 and MAPD50） repolarization were measured and the incidence of arrhythmia induced by transient dilation of the left ventricle was counted. ICI118. 551 （1μmol/L） was administrated through Langendorff equipment. Gi protein inhibitor pertussis toxin（PTX）was administered at a dose of 25/μg/kg ip 48 h before the study. Results After MI, MAPD, MAPD50 and MAPD50 increased by 15.2% ,46.5% and 25.4% respeetively（P〈0. 01）. During stretch, MAPD, MAPD50 and MAPD50 in sham operation group decreased by 12.4%, 18.0% and 16.5% respectively（P〈0.01）. These parameters in MI group decreased by 26.0%, 53.1% and 24.0 % respectively（P〈0.01）, and the rate of the stretch-induced arrhythmias was increased obviously （22.4% vs 10.3%）. After administration of ICI118. 551 or PTX, MAPD, MAPD50 and MAPD50 remained unchanged and the incidence rate of stretch-induced arrhythmias was decreased. Conclusion With dilation of left ventricle by transient balloon inflation in rat infarcted hearts in vitro, MAPD50 and MAPD50 were shortened and arrhythmias were induced. These changes were more obvious in infarcted hearts than in sham operated ones. All these effects could be inhibited by ICI118. 551 or PTX, suggesting that β2-adrenoeeptor may be involved in this process and Gi protein may be one step of this process.