Effects of prolonged propranolol treatment on left ventricular remodeling and oxidative stress after myocardial infarction in rats

Mechanisms determining the benefit of beta blockade in patients with heart failure remain incompletely understood but are assumed consequent to preven tion of deleterious effects of catecholamines. Recent studies have demonstr ated that oxidative stress in congestive heart failure may be related to in creased catecholamine levels, The aim of this study was to examine effects of long-term treatment with propranolol on progression of left ventricular (LV) dysfunction, remodeling and oxidative stress on an experimental model of chronic heart failure. Six weeks after myocardial infarction by coronary ligation, Wistar rats were randomized to two groups: 10 weeks of therapy w ith propranolol (50 mg/kg/day in drinking water) and no treatment (infarcte d controls). A third group was sham-operated rats without treatment. Animal s were anesthetized for hemodynamic measurements, and hearts were then remo ved for histologic analysis, papillary muscle contractility study, and oxid ative stress measurements using thiobarbituric acid reactive substance (TBA RS) determination. Control infarcted rats demonstrated significant alterati ons of hemodynamic parameters and remodeling with increase of heart weight/ body weight, of right ventricular lateral wall thickness, of LV circumferen ce, LV septal area/body weight, and LV papillary muscle weight/body weight as compared with sham, In propranolol-treated rats, hypertrophy of the LV s eptum, papillary muscle, and right ventricle were similar to those of the i nfarcted control. Myocardial oxidative stress was significantly increased i n control infarcted rats compared with sham, and propranolol prevented such oxidative stress increase. Papillary muscle isometric tension parameters w ere not significantly different among groups. Propranolol treatment prevent ed isoprenaline-induced spontaneous papillary muscle activity in vitro. Oxi dative stress is increased in the rat model of heart failure secondary to c oronary ligation. Long-term treatment with propranolol in vivo does not mod ify the compensatory process of hypertrophy but completely abolishes the ox idative stress increase and reduces the increased cardiac sensitivity to ca techolamine-induced arrhythmias observed in this experimental model of hear t failure.