Intrinsic alterations of diaphragm muscle in experimental cardiomyopathy

Diaphragmatic function was investigated in the cardiomyopathic Syrian hamster (CSH) from the dilated Bio 53:58 strain, after long-term therapy with the angiotensin-converting enzyme inhibitor perindopril. Twenty-two 1-month old CSHs were treated during a 5-month period by either oral gavage with perindopril (1 mg/kg/day) (n = 11) or placebo (n = 11). Control hamsters from the F1B strain received placebo (n = 7). Mechanical properties were studied in isolated diaphragm strips electrically stimulated in both twitch and tetanic conditions. Compared with F1B control hamsters, peak active tension and positive (+dP/dtmax) and negative (-dP/dtmax) peaks of isometric tension derivative were significantly depressed in placebo treated CSHs. Compared with placebo-treated CSHs, peak active tension was significantly higher in perindopril-treated CSHs in both twitch (25 +/- 4 vs 16 +/- 1 mN/mm2; p < 0.01) and tetanus modes (56 +/- 4 vs 38 +/- 2 mN/mm2; p < 0.01). Moreover, +dP/dtmax and -dP/dtmax were improved significantly in twitch (p < 0.01 and p < 0.01, respectively) and tetanus modes (p < 0.05 and p < 0.01, respectively). We conclude that, in the CSH, long-term therapy with the angiotensin-converting enzyme inhibitor perindopril helped to preserve the diaphragmatic function.