Silke B, Thompson A, Riddell J G
University Department of Therapeutics and Pharmacology, Queen's University of Belfast, Northern Ireland.
Cardiovasc Drugs Ther. 1997 Mar;11(1):57-61. doi: 10.1023/a:1007799807554.
A double-blind, randomized, placebo-controlled comparison of metoprolol (50 mg) and celiprolol (200 mg) was undertaken in nine normal volunteers. Rest and exercise (supine bicycle) hemodynamics were assessed at 0, 2, 4, 6, and 8 hours following single oral doses of medication administered at weekly intervals. The influence of the ancillary pharmacological properties of metoprolol and celiprolol on cardiac pumping indices was assessed from heart rate and peak aortic acceleration (pkA-Exerdop). Following placebo, the heart rate and pkA increased progressively with exercise duration and workload. Following metoprolol 50 mg, the heart rate (-9.7 beat/min at 75 watts exercise) and pkA decreased. The blunting of acceleration was greater at higher exercise workloads (-6.7 m/sec2 at 75 watts exercise). Celiprolol reduced heart rate (-6.9 beat/min at 75 watts exercise) without a change in pkA. The heart rate/pkA relationship showed significant parallel displacement, downwards after metoprolol but upwards after celiprolol. Thus, for a given heart rate increment there was a greater decrease in pkA after metoprolol compared with celiprolol. The different ancillary pharmacological profiles of metoprolol and celiprolol resulted in contrasting hemodynamic profiles. The observed differences in the heart rate/pkA relationships may be attributable to the peripheral actions of these agents. The therapeutic relevance of the better maintained cardiac pumping indices on celiprolol for ischemic patients with impaired cardiac function warrants further investigation.
在9名正常志愿者中进行了一项美托洛尔(50毫克)和塞利洛尔(200毫克)的双盲、随机、安慰剂对照比较试验。在每周间隔单次口服药物后的0、2、4、6和8小时评估静息和运动(仰卧位自行车)血流动力学。从心率和主动脉峰值加速度(pkA-Exerdop)评估美托洛尔和塞利洛尔的辅助药理学特性对心脏泵血指标的影响。服用安慰剂后,心率和pkA随着运动持续时间和工作量的增加而逐渐升高。服用50毫克美托洛尔后,心率(运动75瓦时为-9.7次/分钟)和pkA降低。在较高运动负荷下,加速度的减弱更为明显(运动75瓦时为-6.7米/秒²)。塞利洛尔降低了心率(运动75瓦时为-6.9次/分钟),而pkA没有变化。心率/pkA关系显示出明显的平行位移,美托洛尔后向下,塞利洛尔后向上。因此,对于给定的心率增加,与塞利洛尔相比,美托洛尔后的pkA下降幅度更大。美托洛尔和塞利洛尔不同的辅助药理学特征导致了不同的血流动力学特征。观察到的心率/pkA关系差异可能归因于这些药物的外周作用。塞利洛尔对心功能受损的缺血患者更好地维持心脏泵血指标的治疗相关性值得进一步研究。