Bussmann W D, Störger H, Hadler D, Reifart N, Fassbinder W, Jungmann E, Kaltenbach M
J Cardiovasc Pharmacol. 1987;9 Suppl 2:S50-60. doi: 10.1097/00005344-198700002-00012.
Twenty-three patients with severe heart failure (NYHA classes III and IV) on treatment with digitalis and diuretics were additionally treated in a randomized double-blind study over a 6-month period with captopril (n = 12; mean daily dose 84 mg) or a placebo (n = 11) and were then reexamined. In the captopril group, the left-ventricular filling pressure decreased by 9 mm Hg (from 23 to 14) at rest and 6 mm Hg (from 35 to 29) during exercise. In the placebo group, there was an increase of 4 mm Hg (from 25 to 29) at rest and 7 mm Hg (from 33 to 40) during exercise; p less than 0.01 (p less than 0.01). In the captopril group, the cardiac index at rest increased 0.7 1/min/m2 (from 2.1 to 2.8) and during exercise 1.2 1/min/m2 (from 2.8 to 4.0). In the placebo group, the increase in cardiac index was considerably less pronounced at rest (= 0.2 1/min/m2; from 1.9 to 2.1) and during exercise (= 0.1 1/min/m2; from 2.7 to 2.8); p less than 0.02 (p less than 0.01). The improved cardiac output had a beneficial effect on the renal blood flow. Hippuran clearance increased by 46 ml/min (from 271 to 318), whereas in the control group it decreased 25 ml/min (from 259 to 234) (p less than 1.02). Both the heart rate and the arterial blood pressure remained constant, whereas the decrease in peripheral vascular resistance was definitely more pronounced in the captopril group (= 562 dyne X s X cm-5, from 1,841 to 1,279) than in the placebo group (= 123 dyne X s X cm-5, from 1,834 to 1,710; p less than 0.02). The heart volume, assessed radiographically, increased slightly in the placebo group, and the left-ventricular end-diastolic diameter remained constant in both groups. In the course of the study, two patients died in the captopril group and three in the placebo group. After six months, eight patients in the captopril group and three in the placebo group had improved by at least one NYHA category. The beneficial effects of captopril are due to its inhibitory effect on the renin-angiotensin system as well as to the inhibition of sympathetic stimulation. Consequently, in the captopril group the quantity of plasma norepinephrine decreased by 188 ng/ml (from 430 to 618); p less than 0.03. The indirect vasodilation caused by this mechanism leads to persistent unloading of the myocardium and an improvement in heart failure without loss of action by counterregulatory mechanisms.
23例正在接受洋地黄和利尿剂治疗的重度心力衰竭（纽约心脏病协会III级和IV级）患者，在一项为期6个月的随机双盲研究中，额外接受卡托普利（n = 12；平均每日剂量84 mg）或安慰剂（n = 11）治疗，之后再次接受检查。在卡托普利组，静息时左心室充盈压下降9 mmHg（从23降至14），运动时下降6 mmHg（从35降至29）。在安慰剂组，静息时升高4 mmHg（从25升至29），运动时升高7 mmHg（从33升至40）；p<0.01（p<0.01）。在卡托普利组，静息时心脏指数增加0.7 l/min/m²（从2.1升至2.8），运动时增加1.2 l/min/m²（从2.8升至4.0）。在安慰剂组，静息时心脏指数增加明显较少（=0.2 l/min/m²；从1.9升至2.1），运动时增加更少（=0.1 l/min/m²；从2.7升至2.8）；p<0.02（p<0.01）。心输出量的改善对肾血流量有有益影响。马尿酸清除率增加46 ml/min（从271升至318），而在对照组中下降25 ml/min（从259降至234）（p<0.02）。心率和动脉血压保持恒定，而卡托普利组外周血管阻力的下降明显更显著（=562达因×秒×厘米⁻⁵，从1841降至1279），高于安慰剂组（=123达因×秒×厘米⁻⁵，从1834降至1710；p<0.02）。通过X线检查评估，安慰剂组心脏容积略有增加，但两组左心室舒张末期直径均保持不变。在研究过程中，卡托普利组有2例患者死亡，安慰剂组有3例患者死亡。6个月后，卡托普利组有8例患者、安慰剂组有3例患者的心功能至少改善了一个纽约心脏病协会分级。卡托普利的有益作用归因于其对肾素-血管紧张素系统的抑制作用以及对交感神经刺激的抑制。因此，在卡托普利组，血浆去甲肾上腺素量减少188 ng/ml（从430降至242）；p<0.03。由该机制引起的间接血管舒张导致心肌持续减负，心力衰竭得到改善，且不会因反调节机制而失去作用。
