[Protective effects of perindopril in an experimental model of cardiomyopathy].
The effects of an angiotensin converting enzyme (ACE) inhibitor on the intrinsic contractility of the myocardium in cardiac failure have not been studied intensively. The authors studied inotropism, lusitropism and economy of contraction in vitro on left ventricular papillary muscle preparations of cardiomyopathic Syrian hamsters (CSH) treated preventively with perindropil, i.e. before overt signs of cardiac failure. The CSH of the dilated Bio 53.58 strain aged 1 month were treated with perindropil 1 mg/Kg/day for 5 months (PE, N = 11) or with placebo (PL, N = 11) and control hamsters of the F1B strain received placebo (C, N = 7). Compared with C, PL had a significant reduction of the maximal velocity of contraction Vmax (p < 0.01) and of total isometric tension (TF/mm2), p < 0.05, and a reduction of the G curve of the hyperbolic Hill Force-Velocity relationship (p < 0.01). The G value is usually greater in models with improved economy of contraction. When compared with PL, PE showed a 68% inhibition of the plasma activity of ACE, a better Vmax (p < 0.05) but an unchanged TF/mm2. The G value was less depressed than that of C (p < 0.05). The velocity of isotonic relaxation (maxVL) and the negative peak of the derivative of the isometric force (-dF/dt max) were significantly lower in the PL than in the C group but these lusitropic abnormalities remained coordinated with those of the contraction phase, indicating the absence of an intrinsic effect on relaxation in cardiomyopathy. Perindopril prevented the reduction of maxVL but not that of -dF/dt max.(ABSTRACT TRUNCATED AT 250 WORDS)
Chemla
D
D
INSERM U275-Loa-Ensta-Ecole polytechnique, Palaiseau.
Scalbert
E
E
Desché
P
P
Pourny
J C
JC
Lambert
F
F
Lecarpentier
Y
Y
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy*; D002985:Clinical Protocols; D006224:Cricetinae; D004195:Disease Models, Animal; D004341:Drug Evaluation; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D009200:Myocardial Contraction / Q000187:drug effects; D020913:Perindopril
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D020913:Perindopril
Effets cardioprotecteurs du périndopril dans un modèle expérimental de cardiomyopathie dilatée.