Selective β1-blockade attenuates post-infarct remodelling without improvement in myocardial energy metabolism and function in rats with heart failure

Objective: To investigate in vivo effects of long-term selective beta(1)-blockade on cardiac energy metabolism, remodelling, function and plasma cytokines in a rat model of post-infarct congestive heart failure (CHF). Methods: Myocardial infarction (MI) was induced in male rats by ligation of the left coronary artery. Three different groups of rats were studied, MI rats treated with metoprolol (n = 17), MI rats treated with saline (n = 14) and sham-operated rats (n = 12). The treatment with metoprolol 1 mg/ kg/h was initiated in the third week post-infarct for a period of 6 weeks. All rats were investigated non-invasively with volume-selective P-31 magnetic resonance spectroscopy and echocardiography for evaluation of left ventricular (LV) energy metabolism, morphology and function. Plasma concentration of IL-1beta and IL-6 and density of beta-adrenergic receptors were analyzed. Results: Metoprolol attenuated the increase in LV dimensions and volumes. Treatment with metoprolol had no effect on PCr/ATP and LV function. Plasma level of IL-1beta was higher and IL-6 was lower in the metoprolol group. Density of P-adrenergic receptors was similar in all three groups. Conclusion: Selective beta-blockade in rats with chronic CHF attenuates post-infarct structural remodelling, without concomitant improvement in myocardial energy metabolism and function. Improvements in myocardial energy metabolism and function do not precede and are not a prerequisite for an anti-remodelling effect of PI-blockade in the setting of chronic CHF. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.