Hemodynamic and Myocardial Metabolic Effects of Captopril, an Angiotensin Converting Enzyme inhibitor, in Acute Myocardial Infarction

Abstract

It has recently been reported that the renin-angiotensin-aldosterone system plays a role in controlling cardiac load in heart failure. Captopril (SQ-14225), an orally active angiotensin converting enzyme inhibitior, was therefore administered in 10 patients with heart failure due to acute myocardial infarction and in dogs with coronary occlusion. In clinical studies, after administration of captopril, oral doses of 25mg, cardiac index increased (2.9±0.8→3.1±0.71/min/m², P<0.05), stroke volume index increased (36.7±2.7→41.4±3.6ml/beat/m²), systolic arterial pressure decreased (139± 14.5→127±42.8mmHg), heart rate decreased (90±7.4→87±2.3beat/min²), pulmonary capillary wedge pressure reduced markedly (20±2.6→13±2.→3mmHg, P<0.01) and systemic vascular resistance reduced (1408±162→1151±148dyne·sec·cm^-5, P<0.05). These effects were started 5 minutes after, reached peak 90-120 minutes after and lasted an average of 5 hours. Plasma renin activity rose after captopril (2.0±0.7→3.9±1.7ng/ml, P<0.05), plasma concentration of angiotensin II fell (140±140→85±91pg/ml) and plasma concentration of aldosterone fell (8.2±4.4→4.7±0.8ng/dl). In five cases, we measured plasma concentration of bradykinin (31±18→34±18pg/dl). It is considered that captopril has a substantial effect on both peripheral vascular resistance and venous capacitance by inhibition of vasoconstriction due to angiotensin II. In experimental studies in dogs, we found coronary sinus flow increased (62±32→83±40ml/min, P<0.01), coronary vascular resistance decreased (2.8±1.2→1.8±0.8mmHg/ml/min) and myocardial oxygen consumption increased (5.7±2.0→8.2±3.3ml/min) in dogs with coronary occlustion. Our study suggests that captopril applied in patient with acute myocardial infarction produces significant improvement in left ventricular function and myocardial metabolism without any serious complication.