Session 5. Pharmacologie cardio-vasculaire (60-72)
BETA-BLOCKER TREATMENT IN EXPERIMENTAL HEART FAILURE IN RATS
P. Mansuy, N. Mougenot, J. F Ramirez-Gil, F. Moreau-Raillecove, D. Rousselot-Bonnefond, M. Komajda, Ph. Lechat.
Service de pharmacologie, Centre Claude Bernard, IFR IPGC, CHU Pitié Salpétrière, 47 bd de l’Hôpital, 75013 Paris.
Mechanisms of beneficial effects of beta-blocker treatment in heart failure (HF) in human remain unclear and based on the antagonism of the potential deleterious effects of catecholamines. Since oxydative stress is increased in HF, and can be induced by catecholamines, part of the beneficial effect of beta-blockers could be related to a reduction of oxydative stress through a reduction of catecholamine release from sympathetic nerve endings. We then tested efficacy of a non selective beta-blocker, propranolol (P) on the experimental model of HF induced in the rat by myocardial infarction secondary to coronary ligation. Three groups of animals were compared: Non infarcted sham (S. n=32), infarcted controls (C, n=30) and propranolol (P) treated animals (45 mg/kg/day, n= 19). P was administrated in drinking water and started six weeks after surgery and given during a six to eight week period. At the time of sacrifice, a sample of non infarcted myocardium (basal area) was removed for indirect evaluation of lipidic peroxydation (TBARS determination). Results: Compared to sham animals, hemodynamic parameters were moderately but significantly impaired in infarcted animals and to a similar extend in both groups. Cardiac remodelling was present in infarcted hearts with left ventricular dilatation and hypertrophy: Left ventricular cross sectional area (cm2, mean ± sem) was 0.07 ± 0.01 (S), 0.14 ± 0.01 (C), and 0.08 ± 0.007 (P), p