Selective beta(1)-blockade improves cardiac bioenergetics and function anddecreases neuroendocrine activation in rats during early postinfarct remodeling

In spite of the solid evidence that beta -blockade reduces mortality and mo rbidity in congestive heart failure (CHF) this therapy continues to be unde rused in clinical praxis, The reason for this may lie in scarcity of knowle dge about the mechanisms of beta -blockade action. The major aim of this st udy was to investigate in vivo whether selective beta (1)-blockade may impr ove cardiac energy metabolism in rats with myocardial infarction in early p ostinfarct remodeling phase. Myocardial infarction (MI) was induced in male Sprague-Dawley rats by ligation of the left coronary artery. Two different groups of rats were studied, rats with MI treated with metoprolol (5 mg/kg /h; n = 9) and rats with MI saline treated (n = 9), The treatment with meto prolol was given by subcutaneously implanted minipumps and was initiated at 3 days postinfarct and during the period of 4 weeks. All rats were investi gated with noninvasive methods P-31 magnetic resonance spectroscopy (MRS) a nd transthoracic echocardiography 3 days after induction of MI and 4 weeks later, Phosphocreatine/ATP ratio was normalized after the treatment with me toprolol while it was 50% lower in the saline group (p < 0.001), In the met oprolol group stroke volume and ejection fraction increased while decelerat ion time of mitral early filling was longer tall p < 0.05), Left ventricula r weight as well as volumes and dimensions were similar between the groups. Plasma levels of noradrenaline (p = 0.058), adrenaline (p < 0.01) and brai n natriuretic peptide (p = 0.09) were lower in the metoprolol group, Select ive <beta>(1)-blockade with high dose of metoprolol initiated in the early postinfarct phase improves myocardial energy metabolism and function and pr events overactivation of sympathetic system, The beneficial effect on myoca rdial bioenergetics may be an important mode of action of beta -blockers wh ich contributes to the clinical benefits of the therapy in CHF. (C) 2001 Ac ademic Press.