Mitrovic V, Mudra H, Bonzel T, Schmidt W, Schlepper M
Kerckhoff-Klinik, Bad Nauheim.
Z Kardiol. 1996 Nov;85(11):828-38.
The hemodynamic and neurohumoral effects of single and multiple doses of intravenous quinaprilat were assessed and compared with placebo in a double-blind design. The study group included 50 patients aged between 33 and 76 years with NYHA Class III and IV heart failure. The patients were randomized into three treatment groups to receive low (0.5 and 1.0 mg), medium (1.0 and 2.5 mg), or high (5.0 and 10.0 mg) intravenous doses of quinaprilat or placebo on day 1, and, based on the responses, q6h on two further days. The hemodynamic parameters were determined by right-heart catheterization. Quinaprilat is the active metabolite of quinapril, an ACE inhibitor with high affinity for the angiotensin converting enzyme, which is formulated for oral application. Compared with placebo, single and multiple doses of quinaprilat increased cardiac index by 25% (p < 0.05) and simultaneously decreased both peripheral vascular resistance by 25% (p < 0.05) and left ventricular filling pressures by 33% (p < 0.05). There was a dose-related decrease in mean right atrial pressure by 47% (p < 0.05) without significant heart rate changes (-3-5 bpm). The mean artery pressure showed a dose-related maximum decrease of 4-9 mm Hg 45-60 min after single-dose quinaprilat and of 7-10 mm Hg (p < 0.05) after repetitive dosing. Maximum changes were observed 15-90 min after drug application. The hemodynamic changes after multiple-dose quinaprilat were similar to those observed following single doses and generally persisted during the total observation period of 6 h. Compared with placebo, quinaprilat reduced ACE activity and angiotensin II and aldosterone concentrations, and increased plasma renin activity. There were no significant changes with regard to plasma catecholamines and the atrial natriuretic factor, although a slight decrease could be observed. The study results obtained in patients with advanced heart failure support both the safety and favorable hemodynamic and neurohumoral effects of intravenous quinaprilat over an observation period of 3 days.
采用双盲设计评估并比较了单次和多次静脉注射喹那普利拉的血流动力学及神经体液效应，并与安慰剂进行对照。研究组包括50例年龄在33至76岁之间、纽约心脏病协会（NYHA）心功能分级为III级和IV级的心力衰竭患者。患者被随机分为三个治疗组，于第1天接受低剂量（0.5和1.0毫克）、中等剂量（1.0和2.5毫克）或高剂量（5.0和10.0毫克）静脉注射喹那普利拉或安慰剂，并根据反应情况在接下来的两天内每6小时给药一次。通过右心导管插入术测定血流动力学参数。喹那普利拉是喹那普利的活性代谢产物，喹那普利是一种对血管紧张素转换酶具有高亲和力的血管紧张素转换酶抑制剂（ACE抑制剂），其剂型为口服制剂。与安慰剂相比，单次和多次剂量的喹那普利拉可使心脏指数增加25%（p<0.05），同时使外周血管阻力降低25%（p<0.05），左心室充盈压降低33%（p<0.05）。平均右心房压力呈剂量相关下降，降幅为47%（p<0.05），心率无显著变化（-3至5次/分钟）。单剂量喹那普利拉给药后45至60分钟，平均动脉压出现与剂量相关的最大降幅，为4至9毫米汞柱，重复给药后为7至10毫米汞柱（p<0.05）。用药后15至90分钟观察到最大变化。多次剂量喹那普利拉后的血流动力学变化与单次给药后观察到的变化相似，且在6小时的总观察期内一般持续存在。与安慰剂相比，喹那普利拉降低了ACE活性、血管紧张素II和醛固酮浓度，并增加了血浆肾素活性。血浆儿茶酚胺和心房利钠因子虽有轻微下降，但无显著变化。在晚期心力衰竭患者中获得的研究结果支持了静脉注射喹那普利拉在3天观察期内的安全性以及良好的血流动力学和神经体液效应。
