Hu K, Gaudron P, Ertl G
Medizinische Klinik II, Klinikum Mannheim der Universität Heidelberg, Germany.
J Am Coll Cardiol. 1998 Mar 1;31(3):692-700. doi: 10.1016/s0735-1097(97)00527-5.
This study was designed to assess the long-term effects of a beta1-selective beta-adrenergic blocking agent on mortality, in vivo hemodynamic function, left ventricular volume and wall stress in post-myocardial infarction (MI) rats.
Beta-blockers have shown beneficial results in clinical studies after MI. However, the underlying mechanism is not yet understood, and experimental studies have shown conflicting results.
Bisoprolol (60 mg/kg body weight per day) was given 30 min or 14 days after MI or sham operation.
The mortality rate was reduced only in early bisoprolol-treated rats (29% vs. 46% in untreated rats, p < 0.05). Heart rate was equally reduced in all treatment groups, and the maximal rate of rise of left ventricular systolic pressure (dP/dt(max)) decreased in sham rats and in rats with a small to moderate infarct size. Stroke volume index was unchanged in sham rats and in rats with a small to moderate infarct with early or late bisoprolol treatment and increased in rats with a large infarct in the late bisoprolol group. Left ventricular volume was increased by bisoprolol in sham rats and rats with a small infarct but not in rats with a large infarct.
Treatments starting early (30 min) or late (14 days) after coronary artery ligation with bisoprolol increased left ventricular volume in sham rats and in rats with a small infarct but not in rats with a large infarct. Late bisoprolol treatment improved stroke volume index, and early bisoprolol treatment reduced diastolic wall stress, in rats with a large myocardial infarct. Thus, bisoprolol effects on remodeling and cardiac performance after myocardial infarction strongly depend on infarct size and timing of treatment. This finding may explain previous controversial results that did not consider infarct size and timing of treatment.
本研究旨在评估β1选择性β肾上腺素能阻滞剂对心肌梗死后（MI）大鼠死亡率、体内血流动力学功能、左心室容积和壁应力的长期影响。
β受体阻滞剂在心肌梗死后的临床研究中已显示出有益效果。然而，其潜在机制尚未明确，且实验研究结果相互矛盾。
在心肌梗死或假手术后30分钟或14天给予比索洛尔（每天60毫克/千克体重）。
仅早期接受比索洛尔治疗的大鼠死亡率降低（29%对未治疗大鼠的46%，p<0.05）。所有治疗组的心率均同等降低，假手术大鼠和梗死面积小至中等的大鼠左心室收缩压最大上升速率（dP/dt(max)）降低。早期或晚期接受比索洛尔治疗的假手术大鼠和梗死面积小至中等的大鼠的每搏输出量指数未改变，而晚期比索洛尔组中梗死面积大的大鼠每搏输出量指数增加。比索洛尔使假手术大鼠和梗死面积小的大鼠左心室容积增加，但梗死面积大的大鼠未增加。
冠状动脉结扎后早期（30分钟）或晚期（14天）用比索洛尔治疗可使假手术大鼠和梗死面积小的大鼠左心室容积增加，但梗死面积大的大鼠未增加。晚期比索洛尔治疗可改善梗死面积大的大鼠的每搏输出量指数，早期比索洛尔治疗可降低梗死面积大的大鼠的舒张期壁应力。因此，比索洛尔对心肌梗死后重塑和心脏功能的影响强烈依赖于梗死面积和治疗时机。这一发现可能解释了以往未考虑梗死面积和治疗时机的有争议的结果。
