Drexler H, Banhardt U, Meinertz T, Wollschläger H, Lehmann M, Just H
Medizinische Klinik III, University of Freiburg, FRG.
Circulation. 1989 Mar;79(3):491-502. doi: 10.1161/01.cir.79.3.491.
To discover the underlying mechanisms involved in the beneficial long-term effects of angiotensin converting enzyme (ACE) inhibitors, we investigated the systemic and peripheral effects of short- and long-term ACE inhibition in patients with chronic heart failure. After assessing the short-term effects and dose titration with cilazapril, a new long-acting ACE inhibitor, 21 patients were randomized to receive either placebo or the ACE inhibitor. Seventeen patients completed the 3-month treatment. Central hemodynamic output, femoral blood flow (measured by thermodilution), oxygen saturation, and lactate and norepinephrine levels were determined simultaneously in the femoral vein and radial artery during treatment and after a 3-month rest and during symptom-limited bicycle exercise. Short-term ACE inhibition improved rest and exercise hemodynamic output, but it did not alter peak femoral blood flow, calculated leg oxygen consumption, or systemic oxygen uptake during exercise, despite significant reduction in femoral norepinephrine extraction and arterial angiotensin levels during exercise. In contrast, long-term ACE inhibition further improved exercise cardiac output and increased leg blood flow (from 2.3 to 2.9 l/min, p less than 0.05), leg oxygen consumption (from 277 to 403 ml/min, p less than 0.05), and systemic oxygen uptake (from 1,133 to 1,453 ml/min, p less than 0.05), whereas these variables remained unchanged with placebo treatment (p less than 0.02 between groups). Moreover, a moderate but significant increase in femoral oxygen extraction occurred after long-term therapy (ACE inhibitor: from 76% to 83%, p less than 0.05; placebo: from 75% to 74%, NS; p less than 0.01 between groups). We conclude that long-term ACE inhibition is clinically beneficial in that it improves blood flow to skeletal muscle during exercise over time. The long-term effects of ACE inhibition are, in part, probably related to peripheral (vascular) mechanisms, for example, by reversing the inability of peripheral vessels to dilate and by improving oxygen utilization.
为了探究血管紧张素转换酶（ACE）抑制剂长期有益作用的潜在机制，我们研究了短期和长期ACE抑制对慢性心力衰竭患者的全身和外周影响。在用新型长效ACE抑制剂西拉普利评估短期效应并进行剂量滴定后，21例患者被随机分为接受安慰剂或ACE抑制剂治疗。17例患者完成了3个月的治疗。在治疗期间、3个月休息后以及症状限制的自行车运动期间，同时测定股静脉和桡动脉的中心血流动力学输出、股血流量（通过热稀释法测量）、血氧饱和度以及乳酸和去甲肾上腺素水平。短期ACE抑制改善了静息和运动时的血流动力学输出，但尽管运动期间股去甲肾上腺素摄取和动脉血管紧张素水平显著降低，却并未改变运动时的股血流峰值、计算得出的腿部耗氧量或全身摄氧量。相比之下，长期ACE抑制进一步改善了运动心输出量，并增加了腿部血流量（从2.3升至2.9升/分钟，p<0.05）、腿部耗氧量（从277升至403毫升/分钟，p<0.05）和全身摄氧量（从1133升至1453毫升/分钟，p<0.05），而安慰剂治疗时这些变量保持不变（组间p<0.02）。此外，长期治疗后股氧摄取有适度但显著的增加（ACE抑制剂组：从76%升至83%，p<0.05；安慰剂组：从75%升至74%，无显著性差异；组间p<0.01）。我们得出结论，长期ACE抑制在临床上是有益的，因为它能随着时间的推移改善运动期间骨骼肌的血流。ACE抑制的长期效应可能部分与外周（血管）机制有关，例如，通过逆转外周血管无法扩张的状态以及改善氧利用。
