Delayed but not immediate captopril therapy improves cardiac function in conscious rats, following myocardial infarction.

After myocardial infarction, the renin-angiotensin system is found to be activated. While this response may be beneficial in acute failure, it could be detrimental in chronic stages. Therefore effects of captopril therapy were investigated during early and later phases after myocardial infarction in conscious rats, chronically instrumented for hemodynamic measurements. Hemodynamics were measured at baseline and after stimulating the heart by a volume load (cardiac function curve). Myocardial infarction decreased baseline cardiac output and impaired cardiac function, without effects on baseline mean arterial pressure, central venous pressure and heart rate. Captopril given 3 to 5 weeks after infarction improved cardiac function in a dose-dependent manner by increasing stroke volume, whereas stroke work was not affected. In contrast, captopril given from 1 to 21 days after infarction did not lead to improved cardiac function; instead, tachycardia together with a decreased stroke volume suggested deterioration, rather than improvement, of cardiac function. These data indicate that captopril therapy in chronically infarcted conscious rats improved cardiac function when treatment was started after completion of the healing process, but that early treatment not only failed to improve ventricular function, but may have a deleterious effect of the heart.