Long-term effects of carvedilol on left ventricular function, remodeling, and expression of cardiac cytokines after large myocardial infarction in the rat

J Cardiovasc Pharmacol. 2002 Jan;39(1):73-87. doi: 10.1097/00005344-200201000-00009.

Abstract

Carvedilol (20 mg/kg, bid) or vehicle was given to rats surviving a myocardial infarction (MI) 24 h (n = 409). In rats with large MI, carvedilol partially preserved left ventricular (LV) function and intrinsic myocardial contractility and reactivity to beta-adrenergic stimulation. Carvedilol led to scar thickening, increased LV hypertrophy, and decreased cardiac fibrosis but did not prevent LV dilatation. Carvedilol reduced cardiac expression of interleukin-1beta but did not prevent cardiac fetal gene re-expression or modify cardiac oxidative stress. Despite these beneficial effects, carvedilol decreased survival (38.8%, versus vehicle, 50.6%) due to excessive early mortality. Thus, post-MI carvedilol has many beneficial effects, however, in this study it increased post-MI mortality, perhaps due to excessive hypotension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Carbazoles / pharmacology*
  • Carvedilol
  • Cytokines / drug effects*
  • Cytokines / metabolism
  • Fibrosis
  • Gas Chromatography-Mass Spectrometry
  • Hemodynamics / drug effects
  • In Vitro Techniques
  • Male
  • Myocardial Contraction / drug effects
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / mortality
  • Myocardial Infarction / physiopathology*
  • Myocardium / pathology
  • Nuclease Protection Assays
  • Oxidative Stress / drug effects
  • Papillary Muscles / drug effects
  • Propanolamines / pharmacology*
  • Rats
  • Rats, Wistar
  • Ventricular Function, Left / drug effects*
  • Ventricular Remodeling / drug effects*

Substances

  • Adrenergic beta-Antagonists
  • Carbazoles
  • Cytokines
  • Propanolamines
  • Carvedilol