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[Protective effects of perindopril in an experimental model of cardiomyopathy]
D Chemla1, E Scalbert, P Desché
1INSERM U275-Loa-Ensta-Ecole polytechnique, Palaiseau.
Insights
Preventive treatment with perindopril, an angiotensin converting enzyme (ACE) inhibitor, improved myocardial contractility in cardiomyopathic hamsters. Perindopril enhanced maximal velocity of contraction and preserved economy of contraction, suggesting a beneficial effect on cardiac function.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- Cardiac failure significantly impairs myocardial contractility.
- The intrinsic effects of angiotensin converting enzyme (ACE) inhibitors on cardiac contractility are not well understood.
Purpose of the Study:
- To investigate the effects of preventive perindopril treatment on myocardial inotropism, lusitropism, and economy of contraction in a model of inherited dilated cardiomyopathy.
Main Methods:
- Left ventricular papillary muscles from cardiomyopathic Syrian hamsters (CSH) and control hamsters were studied in vitro.
- CSH were treated preventively with perindopril or placebo.
- Muscle function parameters including maximal velocity of contraction (Vmax), total isometric tension (TF/mm2), and force-velocity relationship (G value) were measured.
Main Results:
- Placebo-treated CSH showed reduced Vmax, TF/mm2, and G value compared to controls.
- Perindopril treatment resulted in 68% ACE inhibition, improved Vmax, and preserved G value compared to placebo.
- Perindopril prevented the reduction in maximal velocity of isotonic relaxation (maxVL) but not the decrease in -dF/dt max.
Conclusions:
- Preventive perindopril treatment improves intrinsic myocardial contractility and economy of contraction in CSH.
- Perindopril's beneficial effects on cardiac function may extend beyond vasodilation.
- The study highlights the potential of ACE inhibitors in preserving cardiac function in early-stage cardiomyopathy.
Abstract:
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)