Frais M A, Silke B, Ahuja R C, Verma S P, Nelson G I, Taylor S H
J Cardiovasc Pharmacol. 1985 Jan-Feb;7(1):80-5. doi: 10.1097/00005344-198501000-00013.
In patients with acute myocardial infarction the haemodynamic relevance of the ancillary pharmacological properties of cardioselectivity and of intrinsic sympathomimetic activity (ISA) possessed by beta-blocking drugs is unclear. The dose-response effects of atenolol and acebutolol, two cardioselective compounds, the latter also possessing a degree of ISA, were therefore compared in a single-blind, dose-response, crossover study in patients within 18 h of suffering an uncomplicated acute myocardial infarction. The logarithmic cumulative dosage schedule achieved plasma concentrations in the clinical therapeutic ranges for both atenolol (0.05 +/- 0.04-0.19 +/- 0.03 micrograms/ml) and acebutolol (0.22 +/- 0.14-0.8 +/- 0.29 micrograms/ml). Incremental doses of intravenous atenolol (cumulative, 1-8 mg) resulted in significant decreases in systolic blood pressure, heart rate, cardiac output, stroke volume, and stroke work index (p less than 0.01 for each). Pulmonary artery occluded pressure (p less than 0.05) and systemic vascular resistance (p less than 0.01) increased. Incremental doses of intravenous acebutolol (cumulative, 10-80 mg) also resulted in significant decreases in systolic blood pressure, heart rate, cardiac output, stroke volume, and stroke work index (p less than 0.01 for each). Systemic vascular resistance increased (p less than 0.01); there was no consistent change in the pulmonary artery occluded pressure. Within the limits of the experimental protocol, the additional property of ISA possessed by acebutolol resulted in no statistically significant haemodynamic differences from atenolol. This may reflect either an insufficient degree of ISA possessed by acebutolol to confirm the original hypothesis, or its haemodynamic irrelevance in the presence of the increased sympathetic tone that is frequently present following acute myocardial infarction.
在急性心肌梗死患者中，β受体阻滞剂所具有的心脏选择性及内在拟交感活性（ISA）等辅助药理学特性对血流动力学的影响尚不清楚。因此，在一项单盲、剂量反应、交叉研究中，比较了两种具有心脏选择性的化合物阿替洛尔和美托洛尔的剂量反应效应，后者也具有一定程度的ISA，研究对象为发生无并发症急性心肌梗死18小时内的患者。对数累积剂量方案使阿替洛尔（0.05±0.04 - 0.19±0.03微克/毫升）和美托洛尔（0.22±0.14 - 0.8±0.29微克/毫升）的血浆浓度达到临床治疗范围。静脉注射递增剂量的阿替洛尔（累积剂量1 - 8毫克）导致收缩压、心率、心输出量、每搏量和每搏功指数显著降低（每项p均<0.01）。肺动脉闭塞压（p<0.05）和全身血管阻力（p<0.01）升高。静脉注射递增剂量的美托洛尔（累积剂量10 - 80毫克）也导致收缩压、心率、心输出量、每搏量和每搏功指数显著降低（每项p均<0.01）。全身血管阻力增加（p<0.01）；肺动脉闭塞压无一致变化。在实验方案的范围内，美托洛尔所具有的ISA附加特性与阿替洛尔相比，在血流动力学上无统计学显著差异。这可能反映了美托洛尔所具有的ISA程度不足以证实最初的假设，或者在急性心肌梗死后经常出现的交感神经张力增加的情况下，其血流动力学无关紧要。
