美托洛尔对急性心肌梗死大鼠心房重构的影响

Effects of metoprolol on atrial remodeling in rats with acute myocardial infarction

目的:探讨β1受体阻滞剂美托洛尔对急性前壁心肌梗死大鼠心房结构和电重构的影响。方法:通过结扎冠状动脉前降支制备前壁心肌梗死大鼠模型。将存活大鼠随机分为心肌梗死组(MI组,n=6)、美托洛尔组(MI+M组,n=6),另设假手术组(Sham组,n=6)。MI+M组术后24 h给予美托洛尔10 mg.kg-1.d-1灌胃,连续28 d。对各组大鼠行超声心动图及心房电生理检查。结果:术后28 d,MI组与Sham组相比,左室舒张末期内径(LVEDD)、左房内径(LAD)增大,缩短分数(FS)明显降低,且P波时限最大值(Pmax值)、P波离散度(Pd值)增加,心房有效不应期(AERP)减小,AERP-频率适应性消失,房性心律失常诱发率增高(P均<0.05)。MI+M组与MI组相比,上述超声指标均有改善,Pmax值增加,Pd值减小,AERP延长,AERP-频率适应性恢复,房性心律失常诱发率减低(P均<0.05)。结论:美托洛尔能改善心肌梗死大鼠的心房结构重构和电重构,减少心肌梗死后房性心律失常的发生率。

Objective：This study was to investigate whether metoprolol, a β1-blocker can improve atrial remodeling in rats after acute myocardial infarction （MI）. Methods： 12 rats underwent left coronary artery ligation and were randomized into M1 group （MI group, n = 6） and metoprlol treatment group （MI＋ M group, n = 6） in which metoprolol was given orally at 10 mg ·kg· d^-1 Another sham operated group （Sham group, n = 6） served as controls. After 28-day observation period, echocardiography, ECG and invasive electrophysiology were performed. Results：Twenty-eight days after MI, infarcted rats demonstrated dilated left ventricle and atrium as evidenced by increases in left ventricular end-diastolic dimension （LVEDD）, left atrial diameter （LAD） and lower fractional shortening （FS） compared with sham operated rats （ P〈0.05, respectively）. The structural changes in MI group were associated with longer maximal P wave duration （Pmax） and dispersion （Pd） compared with Sham group （P〈0.05, respectively）. Furthermore, shortened AERP and its impaired ratedaptation in MI group （ P〈0.05, vs. Sham group, respectively） led to increased incidence of atrial arrhythmias, including atrial fibrillation and flutter, which were induced by either atrial overdrive pacing or programmed stimulation, when compared with that in Sham group （P〈0.05）. Metoprolol not only resulted in reversal of LVEDD and LAD in MI rats, but also significantly improved rate-adaptation of AERP which in turn decreased the incidence of atrial arrhythmias （P〈0.05, respectively）. Conclusion： Atrial structural and electrical remodeling in rats after acute MI can be attenuated by metoprolol, which is associated with lower incidence of atrial arrhythymias after MI.