Jain P, Lillis O, Cohn P F
Department of Medicine, State University of New York, Stony Brook 11794-8171.
Am Heart J. 1994 Apr;127(4 Pt 1):764-73. doi: 10.1016/0002-8703(94)90542-8.
The effects of metoprolol on early infarct expansion after acute myocardial infarction were studied in rats (n = 54) that underwent either left coronary artery ligation (MI) or sham operation. Immediately after surgery, the rats received either metoprolol (M) by mouth, which had been dissolved in drinking water, for 72 hours supplemented with three intraperitoneal doses over the first 24 hours or no treatment (H2O). Three days after the initial surgery, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressure-volume curves were obtained. The hearts were then fixed at a constant pressure and analyzed morphometrically. Infarct size was nonsignificantly lower in the metoprolol-treated group compared with the untreated group (38% +/- 5% MI-M vs 48% +/- 3% MI-H2O, p = 0.10) Compared with infarcted untreated rats, infarcted metoprolol-treated rats had a lower heart rate (322 +/- 13 beats/min MI-M vs 452 +/- 19 beats/min MI-H2O, p < 0.001), lower left ventricular systolic pressure (63 +/- 4 mm Hg MI-M vs 90 +/- 6 mm Hg MI-H2O, p = 0.004), and lower +dp/dt (1340 +/- 169 mm Hg/sec MI-M vs 2872 +/- 273 mm Hg/sec MI-H2O, p < 0.001), but left ventricular end-diastolic pressure and cardiac index did not differ between the two groups. Left ventricular weight corrected for body weight was higher in infarcted rats treated with metoprolol compared with infarcted untreated rats (2.76 +/- 0.07 gm/kg MI-M vs 2.41 +/- 0.09 gm/kg MI-H2O, p < 0.05). The initial slope of the pressure-volume relationship Ki, an index of operative volume stiffness, was lower in infarcted rats treated with metoprolol compared with infarcted untreated rats (p = 0.03). There were, however, no significant differences in the expansion index, thinning ratio, or left ventricular volume between the two infarcted groups. Thus metoprolol therapy begun in the immediate postinfarction period promotes an increase in left ventricular weight and reduces operative volume stiffness but has no significant effect on indexes of early infarct expansion.
在接受左冠状动脉结扎（心肌梗死，MI）或假手术的大鼠（n = 54）中研究了美托洛尔对急性心肌梗死后早期梗死扩展的影响。手术后立即给予大鼠口服溶解于饮用水中的美托洛尔（M），持续72小时，并在最初24小时内额外给予三次腹腔注射剂量，或不进行治疗（H2O）。初次手术后三天，在容量负荷前后进行血流动力学测量。处死大鼠，取出心脏，获得被动压力-容积曲线。然后将心脏固定在恒定压力下并进行形态计量学分析。与未治疗组相比，美托洛尔治疗组的梗死面积略低（MI-M组为38%±5%，MI-H2O组为48%±3%，p = 0.10）。与未治疗的梗死大鼠相比，美托洛尔治疗的梗死大鼠心率较低（MI-M组为322±13次/分钟，MI-H2O组为452±19次/分钟，p < 0.001），左心室收缩压较低（MI-M组为63±4 mmHg，MI-H2O组为90±6 mmHg，p = 0.004），+dp/dt较低（MI-M组为1340±169 mmHg/秒，MI-H2O组为2872±273 mmHg/秒，p < 0.001），但两组之间的左心室舒张末期压力和心脏指数无差异。与未治疗的梗死大鼠相比，美托洛尔治疗的梗死大鼠经体重校正后的左心室重量更高（MI-M组为2.76±0.07 g/kg，MI-H2O组为2.41±0.09 g/kg，p < 0.05）。压力-容积关系的初始斜率Ki（手术容积硬度指数）在美托洛尔治疗的梗死大鼠中低于未治疗的梗死大鼠（p = 0.03）。然而，两个梗死组之间的扩展指数、变薄率或左心室容积无显著差异。因此，在心肌梗死后立即开始的美托洛尔治疗可促进左心室重量增加并降低手术容积硬度，但对早期梗死扩展指标无显著影响。
