Zmudka K, Dubiel J, Pieniazek P, Dudek D, Kocurek A, Trebacz J, Grodecki J, Flameng W, de Geest H
Department of Hemodynamics and Angiocardiography, Jagiellonian University, Cracow, Poland.
J Physiol Pharmacol. 1998 Sep;49(3):333-52.
To evaluate the extent to which the protective effect of metoprolol was accompanied by changes in myocardial oxygen consumption and metabolism, thrombotic occlusion of coronary artery followed by infusion of metoprolol or placebo was performed in twenty four German Shepherds. To restore a coronary blood flow rt-PA was administered. Plasma levels of oxygen, glucose, lactic acid, non esterified fatty acids, triacylglyceride and adenosine breakdown products were measured before and at the end of the occlusion and in the early and late reperfusion periods. Regional myocardial blood flow was measured by means of radioactive tracer microspheres. Infarct size was estimated after perfusion and staining of excised hearts with Evans blue. Plasma levels of metoprolol were determinated before the end of occlusion and during reperfusion and therapeutic concentrations were confirmed. The infarct size was smaller in dogs receiving metoprolol (21.6 +/- 20.7 vs 43.0 +/- 17.3% p. < 0.02). Coronary collateral blood flow was greater in metoprolol than in placebo dogs (18.68 +/- 7.58 vs 11.05 +/- 6.10 ml/min/100g, p. < 0.01). As a consequence of myocardial ischemia a shift toward carbohydrate utilization, the myocardial lactate release and the accompanying symptoms of diminished myocardial lipid uptake were observed. A washout of adenosine degradation products during early reperfusion was also noticed. In beta 1 blocked animals the reduction of myocardial oxygen consumption and preserved myocardial uptake of lactate and non esterified fatty acids were documented.
为评估美托洛尔的保护作用在多大程度上伴随着心肌氧消耗和代谢的变化,对24只德国牧羊犬进行冠状动脉血栓闭塞,随后输注美托洛尔或安慰剂。为恢复冠状动脉血流,给予重组组织型纤溶酶原激活剂(rt-PA)。在闭塞前、闭塞结束时以及再灌注早期和晚期测量血浆中的氧、葡萄糖、乳酸、非酯化脂肪酸、三酰甘油和腺苷分解产物的水平。通过放射性示踪微球测量局部心肌血流量。在用伊文思蓝灌注和染色切除的心脏后估计梗死面积。在闭塞结束前和再灌注期间测定美托洛尔的血浆水平,并确认治疗浓度。接受美托洛尔的犬梗死面积较小(21.6±20.7对43.0±17.3%,p<0.02)。美托洛尔组的冠状动脉侧支血流量大于安慰剂组犬(18.68±7.58对11.05±6.10 ml/min/100g,p<0.01)。由于心肌缺血,观察到向碳水化合物利用的转变、心肌乳酸释放以及伴随的心肌脂质摄取减少的症状。在再灌注早期还注意到腺苷降解产物的清除。在β1受体阻断的动物中,记录到心肌氧消耗减少以及心肌对乳酸和非酯化脂肪酸摄取的保留。