Selective beta1-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 beta1-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-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 beta-adrenergic receptors was similar in all three groups.


CONCLUSIONS
Selective beta1-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 beta1-blockade in the setting of chronic CHF.
Omerovic
E
E
Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy at Gothenburg University, 413 45 Gothenburg, Sweden. elmir@wlab.gu.se
Bollano
E
E
Soussi
B
B
Waagstein
F
F
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004452:Echocardiography; D004734:Energy Metabolism / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008790:Metoprolol / Q000494:pharmacology / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000032:analysis / Q000187:drug effects; D012965:Sodium Chloride / Q000008:administration & dosage; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D007375:Interleukin-1; D015850:Interleukin-6; D018342:Receptors, Adrenergic, beta-1; D012965:Sodium Chloride; D008790:Metoprolol