EFFECTS OF LONG-TERM THERAPY WITH ACE-INHIBITORS, CAPTOPRIL, ENALAPRIL AND TRANDOLAPRIL, ON MYOCARDIAL ENERGY-METABOLISM IN RATS WITH HEART-FAILURE FOLLOWING MYOCARDIAL-INFARCTION
EFFECTS OF LONG-TERM THERAPY WITH ACE-INHIBITORS, CAPTOPRIL, ENALAPRIL AND TRANDOLAPRIL, ON MYOCARDIAL ENERGY-METABOLISM IN RATS WITH HEART-FAILURE FOLLOWING MYOCARDIAL-INFARCTION
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DOI：
10.1016/s0022-2828(95)91551-6
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发表时间：
1995-10-01
影响因子：
5
通讯作者：
TAKEO, S
中科院分区：
文献类型：
--
作者：
SANBE, A;TANONAKA, K;TAKEO, S
虽然血管紧张素转换酶（ACE）抑制剂的药物治疗已被证明是有效的心力衰竭（HF）患者，这种影响的实验基础尚未得到解决。在本研究中，HF动物在手术后第2 - 12周口服10 mg/kg/天的卡托普利、10 mg/kg/天的依那普利和3 mg/kg/天的群多普利，通过永久性阻塞大鼠左冠状动脉起始处2 mm处诱导HF，用ACE抑制剂治疗HF大鼠可增强平均动脉血压的降低，减弱左心室舒张末期压（前负荷的间接标志物）的升高，并减少了HF动物的心输出量和每搏输出量指数的降低。还逆转了HF动物存活的左心室和右心室的ATP、磷酸肌酸、肌酸和线粒体耗氧速率的降低。ACE抑制剂对HF大鼠心输出量指数和高能磷酸盐水平的改善与线粒体耗氧率的恢复有关。在假手术动物中，用ACE抑制剂治疗降低了平均动脉压和左心室收缩压，但没有降低心肌能量代谢的代谢变量。本研究结果为ACE抑制剂治疗改善慢性心力衰竭实验动物的心功能和心肌能量代谢提供了证据。ACE抑制剂长期治疗获益的机制可能归因于线粒体功能的恢复或保留以及前负荷的减少。(C)1995年学术出版社
Although pharmacological therapy with angiotensin converting enzyme (ACE) inhibitors has proved to be effective in patients with heart failure (HF), the experimental basis of this effect has not yet been addressed. In the present study, animals with HF were treated with an oral administration of 10 mg/kg/day captopril, 10 mg/kg/day enalapril and 3 mg/kg/day trandolapril from the 2nd to 12th week after the operation, HF was induced by permanent occlusion of the left coronary artery of the rat at 2 mm from its origin, Treatment of the HF rats with the ACE inhibitors enhanced the decrease in mean arterial blood pressure, attenuated the rise in left ventricular end-diastolic pressure, an indirect marker of preload, and diminished the reduction in cardiac output and stroke volume indices of the HF animal, Treatment. also reversed the reduction in ATP, creatine phosphate, creatine and the mitochondrial oxygen consumption rate of the viable left and right ventricles of the HF animal. The improvement of the cardiac output index and high-energy phosphate levels of the HF rat by the ACE inhibitors was associated with the recovery of the mitochondrial oxygen consumption rate. In sham-operated animals, treatment with the ACE inhibitors reduced mean arterial pressure and left ventricular systolic pressure, but not metabolic variables concerning myocardial energy metabolism. The present results provide evidence that ACE inhibitor therapy improves cardiac function and myocardial energy metabolism of experimental animals with chronic heart failure. The mechanism underlying the benefit of long-term treatment with ACE inhibitors is probably attributable to recovery or preservation of the mitochondrial function and reduction in preload. (C) 1995 Academic Press Limited