Andersson B, Lomsky M, Waagstein F
Wallenberg Laboratory for Cardiovascular Research, Salgrenska Sjukhuset, University of Göteborg, Sweden.
Eur Heart J. 1993 Oct;14(10):1375-85. doi: 10.1093/eurheartj/14.10.1375.
The present study was performed to find possible mechanisms linking the early effects of beta-blockade with the observed long-term effects in patients with heart failure. In 57 patients with heart failure, 13 +/- 3.1 mg of metoprolol was given intravenously. The patients were investigated by invasive haemodynamics (n = 34), including collection of myocardial metabolic data during atrial pacing stress (n = 16), by radionuclide angiography during physiological atrial pacing (n = 13), and by a bedside evaluation (n = 10). Diastolic function, measured by early peak filling rate, followed changes in heart rate, but was similar when heart rate was held constant by atrial pacing before and after beta-blockade. Following beta-blockade and slower heart rates, diastolic filling volumes were redistributed to late diastole. Metoprolol induced a parallel decrease in coronary sinus flow and myocardial oxygen consumption. Myocardial oxygen consumption following beta-blockade decreased both during spontaneous rhythm (25 +/- 15 to 16 +/- 8.8 ml min-1; P = 0.006), and during atrial pacing stress (30 +/- 13 to 23 +/- 11 ml.min-1; P = 0.004). Cardiac index decreased owing to reduction of heart rate (2.3 +/- 1.0 to 1.9 +/- 0.64 l.min-1.m2; P = 0.0003), while left ventricular filling pressure was unchanged. Ejection fraction and ventricular volumes were unaltered following atrial pacing or beta-blockade. There was a reflex increase in noradrenaline concentration after beta-blockade injection (0.96 +/- 0.66 to 1.20 +/- 0.91 nmol.l-1; P = 0.002), whereas myocardial noradrenaline overflow was unchanged. There was a trend towards an increase in myocardial lactate consumption after beta-blockade administration during atrial pacing stress. It is suggested that the surprisingly good tolerability seen after acute administration of beta-blockers to patients with severe heart failure may be explained by prolongation of the diastolic filling phase, which outweighs the negative inotropic effects. The reduced myocardial metabolic demand may allow the failing myocardium to recover and explain the excellent long-term effect on heart function following beta-blockade treatment.
本研究旨在探寻β受体阻滞剂早期效应与心力衰竭患者所观察到的长期效应之间可能的关联机制。对57例心力衰竭患者静脉注射13±3.1毫克美托洛尔。通过有创血流动力学检查（n = 34）对患者进行研究，包括在心房起搏应激期间收集心肌代谢数据（n = 16），通过生理性心房起搏期间的放射性核素血管造影（n = 13）以及床边评估（n = 10）。以早期峰值充盈率测量的舒张功能随心率变化，但在β受体阻滞剂前后通过心房起搏使心率保持恒定时则相似。在β受体阻滞剂治疗且心率减慢后，舒张期充盈量重新分布至舒张晚期。美托洛尔使冠状窦血流和心肌氧耗平行降低。β受体阻滞剂治疗后，在自主心律期间（从25±15降至16±8.8毫升·分钟-1；P = 0.006）以及在心房起搏应激期间（从30±13降至23±11毫升·分钟-1；P = 0.004）心肌氧耗均降低。由于心率降低，心脏指数下降（从2.3±1.0降至1.9±0.64升·分钟-1·平方米；P = 0.0003），而左心室充盈压未改变。心房起搏或β受体阻滞剂治疗后射血分数和心室容积未改变。注射β受体阻滞剂后去甲肾上腺素浓度有反射性升高（从0.96±0.66升至1.20±0.91纳摩尔·升-1；P = 0.002），而心肌去甲肾上腺素溢出未改变。在心房起搏应激期间给予β受体阻滞剂后，心肌乳酸消耗有增加趋势。提示对重度心力衰竭患者急性给予β受体阻滞剂后所观察到的惊人良好耐受性，可能是由于舒张期充盈期延长，这一作用超过了负性肌力作用。心肌代谢需求降低可能使衰竭心肌得以恢复，并解释了β受体阻滞剂治疗后对心脏功能的出色长期效果。
