Selective beta1-blockade attenuates post-infarct remodelling without improvement in myocardial energy metabolism and function in rats with heart failure

Eur J Heart Fail. 2003 Dec;5(6):725-32. doi: 10.1016/s1388-9842(03)00153-3.

Abstract

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / therapeutic use*
  • Analysis of Variance
  • Animals
  • Disease Models, Animal
  • Echocardiography
  • Energy Metabolism / drug effects*
  • Heart Failure / drug therapy*
  • Heart Failure / metabolism
  • Heart Failure / physiopathology
  • Heart Ventricles / drug effects
  • Heart Ventricles / metabolism
  • Interleukin-1 / blood
  • Interleukin-6 / blood
  • Magnetic Resonance Spectroscopy
  • Male
  • Metoprolol / pharmacology
  • Metoprolol / therapeutic use*
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, beta-1 / analysis
  • Receptors, Adrenergic, beta-1 / drug effects
  • Sodium Chloride / administration & dosage
  • Ventricular Function, Left / drug effects*
  • Ventricular Remodeling / drug effects*

Substances

  • Adrenergic beta-Antagonists
  • Interleukin-1
  • Interleukin-6
  • Receptors, Adrenergic, beta-1
  • Sodium Chloride
  • Metoprolol