MYOCARDIAL EFFECTS OF EARLY THERAPY WITH PERINDOPRIL DURING EXPERIMENTAL CARDIOMYOPATHY

The effects of chronic angiotensin-converting enzyme (ACE) inhibition on intrinsic myocardial contractility of the failing myocardium poorly documented. In the present study, inotropy, lusitropy, and economy of force generation were studied in vitro in papillary muscles from cardiomyopathic Syrian hamster (CSH) under early perindopril therapy, i.e., therapy begun at a stage when experimental heart failure was not yet observed. One-month-old CSH from the dilated strain Bio 53.58 were randomly treated over a 5-mouth period with either the ACE inhibitor perindopril 1 mg/kg/day (n = 11) or placebo (n = 11), and 7 age-matched controls were given placebo. Compared with control, placebo had a lower maximum shortening velocity (V(max)) (p < 0.01) and normalized total force (p < 0.05), and a lower curvature of the force-velocity relationship (p < 0.01). It has been shown that the higher the value of the curvature, the better the myothermal economy of force generation. Compared with placebo, perindopril had a 68% inhibition of plasma ACE activity and a greater V(max) (p < 0.05), whereas total force/mm2 was similar. This resulted in a lesser decrease of the curvature compared to control (p < 0. 05). Placebo had a decreased peak lengthening velocity and rate of force decline. However, compared to control, no intrinsic abnormalities of the relaxation phase were observed in either placebo or perindopril when relaxation parameters were corrected for the lower systolic performance. These results indicate that (1) the low inotropic state observed in CSH was associated with a depressed lusitropic state and a decreased myothermal economy of cardiac contraction; (2) early therapy with ACE inhibitor helped to preserve myocardial contractility and economy of force generation; and (3) no intrinsic modification of relaxation phase was observable in both placebo-treated and perindopril-treated CSH.