© 2003 European Society of Cardiology
Selective β1-blockade attenuates post-infarct remodelling without improvement in myocardial energy metabolism and function in rats with heart failure
a Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy at Gothenburg University 413 45 Gothenburg, Sweden
b Lundberg Bioanalysis Laboratory, Sahlgrenska Academy at Gothenburg University 413 45 Gothenburg, Sweden
* Corresponding author. Tel.: +46-31-342-41-58; fax: +46-31-82-37-62. E-mail address: elmir{at}wlab.gu.se
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Abstract |
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Objective: To investigate in vivo effects of long-term selective β1-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 31P magnetic resonance spectroscopy and echocardiography for evaluation of left ventricular (LV) energy metabolism, morphology and function. Plasma concentration of IL-1β and IL-6 and density of β-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-1β was higher and IL-6 was lower in the metoprolol group. Density of β-adrenergic receptors was similar in all three groups.
Conclusion: Selective β1-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 β1-blockade in the setting of chronic CHF.
Key Words: β-Blockade • Congestive heart failure • Cardiac remodelling • Energy metabolism • 31P magnetic resonance spectroscopy
Received March 7, 2003; Revised May 12, 2003; Accepted July 30, 2003
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