Influence of chronic captopril therapy on the mechanical performance of the infarcted rat heart

Abstract

The influence of angiotensin converting enzyme inhibition of hemodynamic changes, development of postinfarction myocardial hypertrophy and left ventricular performance was studied in rats. Infarction was produced under ether anaesthesia by ligature of the descending anterior branches of the left coronary artery. Control rats were submitted to a sham surgery. Groups of infarcted (Inf) and sham-operated control (SO) animals were daily treated with intraperitoneal injections of captopril (Cap, 30 mg kg −) or saline (Sal) for 4–5 weeks. This Cap dose produced a similar decrease in arterial blood pressure in Inf and SO animals. The intraventricular pressures measured in anaesthetized rats showed a marked elevation in the right ventricular systolic (38±4 mmHg) and end diastolic (4±1 mmHg) pressures in the Inf group compared with the SO group (24±1 mmHg and 1±0.4 mmHg, respectively). Cap did not change the pressure overload in the right ventricle. In the left ventricle, however, the end diastolic pressure of the Inf group under Cap was significantly reduced in relation to Sal (12±3 mmHg and 19±2 mmHg, respectively, P<0.05). The post infarction myocardial hypertrophy was depressed by Cap only in the right heart chambers. Thus the right ventricular weight to body weight ratio (mg/g) increased from 0.560.03 in the SO-Sal group to 0.96±0.07 ( P<0.05) in the Inf-Sal group and decreased to 0.73±0.04 ( P<0.05) in the Inf group under Cap. The infarction-induced hypertrophy of the left heart chambers was unaffected by Cap. Left ventricular function was assessed in the hearts perfused in vitro according to the Langendorff technique. The peak isovolumic systolic pressure (ISP) developed at different diastolic pressures (0–30 mmHg) and Ca 2+ concentrations (0.62 and 1.25 mm) was measured. The ISP and the positive inotropic response to Ca 2+ was similarly depressed in both groups of infarcted hearts. Thus the chronic administration of Cap to Inf rats reduces the left ventricular filling pressure but does not reduce the postinfarction pulmonary hypertension. Despite this latter finding, Cap therapy was able to significantly reduce the post-infarction hypertrophy in both right heart chambers. Cap therapy did not change significantly left ventricular systolic function and Ca 2+ responsiveness of the myocardium surviving to infarction.