Pfeffer J M, Pfeffer M A
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Am J Med. 1988 Mar 11;84(3A):37-44. doi: 10.1016/0002-9343(88)90203-3.
The prevention or attenuation of the development of heart failure by the angiotensin converting enzyme inhibitor captopril was examined in two animal models, spontaneously hypertensive rats and rats with myocardial infarction produced by coronary artery ligation. In 24-month-old female spontaneously hypertensive rats with marked left ventricular hypertrophy, cardiac output was reduced despite an increase in ventricular volume, resulting in a greatly reduced ejection fraction. Treatment with captopril from 14 to 24 months of age maintained forward output and prevented ventricular dilatation so that ejection fraction remained normal; left ventricular hypertrophy regressed to levels observed in six-month-old spontaneously hypertensive rats. In rats with moderate and large infarcts three months after ligation, left ventricular filling pressures were elevated, forward output was reduced, and ventricular volumes were greatly increased. Long-term therapy with captopril maintained filling pressures within normal limits and maintained forward output from a lesser dilated left ventricle to yield an ejection fraction that was elevated compared with that in untreated rats. Thus, the potentially deleterious remodeling of the left ventricle in heart failure, an extensive increase in mass and chamber volume, can be favorably altered by long-term angiotensin converting enzyme inhibition (captopril) with salutary effects on hemodynamics.
在两种动物模型，即自发性高血压大鼠和冠状动脉结扎所致心肌梗死大鼠中，研究了血管紧张素转换酶抑制剂卡托普利对心力衰竭发展的预防或减轻作用。在24月龄有明显左心室肥厚的雌性自发性高血压大鼠中，尽管心室容积增加，但心输出量降低，导致射血分数大幅降低。14至24月龄时用卡托普利治疗可维持前向输出并防止心室扩张，从而使射血分数保持正常；左心室肥厚消退至6月龄自发性高血压大鼠所观察到的水平。在结扎后3个月有中度和大面积梗死的大鼠中，左心室充盈压升高，前向输出降低，心室容积大幅增加。卡托普利长期治疗可使充盈压维持在正常范围内，并维持较小扩张的左心室的前向输出，从而产生与未治疗大鼠相比升高的射血分数。因此，心力衰竭时左心室潜在有害的重塑，即质量和腔室容积的广泛增加，可通过长期血管紧张素转换酶抑制（卡托普利）得到有利改变，对血流动力学产生有益影响。
