Selective β1-Blockade Improves Cardiac Bioenergetics and Function and Decreases Neuroendocrine Activation in Rats during Early Postinfarct Remodeling

• Published in: Biochemical and biophysical research communications Vol. 281; no. 2; pp. 491 - 498
• Main Authors: Omerovic, E., Bollano, E., Mobini, R., Madhu, B., Kujacic, V., Soussi, B., Hjalmarson, Å, Waagstein, F.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 23.02.2001
• Subjects: adrenergic antagonists; cellular; energy metabolism; experimental; heart; heart failure; NMR; pathophysiology; remodeling; heart failure; adrenergic antagonists; NMR; remodeling; cellular; pathophysiology; experimental; heart; energy metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2001.4336

In spite of the solid evidence that β-blockade reduces mortality and morbidity in congestive heart failure (CHF) this therapy continues to be underused in clinical praxis. The reason for this may lie in scarcity of knowledge about the mechanisms of β-blockade action. The major aim of this study was to investigate in vivo whether selective β1-blockade may improve cardiac energy metabolism in rats with myocardial infarction in early postinfarct 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 metoprolol was given by subcutaneously implanted minipumps and was initiated at 3 days postinfarct and during the period of 4 weeks. All rats were investigated with noninvasive methods 31P magnetic resonance spectroscopy (MRS) and transthoracic echocardiography 3 days after induction of MI and 4 weeks later. Phosphocreatine/ATP ratio was normalized after the treatment with metoprolol while it was 50% lower in the saline group (p < 0.001). In the metoprolol group stroke volume and ejection fraction increased while deceleration time of mitral early filling was longer (all p < 0.05). Left ventricular weight as well as volumes and dimensions were similar between the groups. Plasma levels of noradrenaline (p = 0.058), adrenaline (p < 0.01) and brain natriuretic peptide (p = 0.09) were lower in the metoprolol group. Selective β1-blockade with high dose of metoprolol initiated in the early postinfarct phase improves myocardial energy metabolism and function and prevents overactivation of sympathetic system. The beneficial effect on myocardial bioenergetics may be an important mode of action of β-blockers which contributes to the clinical benefits of the therapy in CHF.