Low dose carvedilol inhibits progression of heart failure in rats with dilated cardiomyopathy

Br J Pharmacol. 2000 Aug;130(7):1489-95. doi: 10.1038/sj.bjp.0703450.

Abstract

The cardioprotective properties of carvedilol (a vasodilating beta-adrenoceptor blocking agent) were studied in a rat model of dilated cardiomyopathy induced by autoimmune myocarditis. Twenty-eight days after immunization, surviving Lewis rats (32/43=74%) were divided into three groups to be given 2 mg kg(-1) day(-1) (Group-C2, n=10) or 20 mg kg(-1) day(-1) (Group-C20, n=10) of carvedilol, or vehicle (0.5% methylcellulose, Group-V, n=12). After oral administration for 2 months, body weight, heart weight (HW), heart rate (HR), rat alpha-atrial natriuretic peptide (r-ANP) in blood, central venous pressure (CVP), mean blood pressure (mean BP), peak left ventricular pressure (LVP), left ventricular end-diastolic pressure (LVEDP), +/-dP dt(-1) and area of myocardial fibrosis were measured. Values were compared with those for normal Lewis rats (Group-N, n=10). Two out of 12 (17%) rats in Group-V died from day 28 to day 42 after immunization. No rat died in Groups-C2, -C20 and -N. Although the CVP, mean BP, LVP and +/-dP dt(-1) did not differ among the three groups, the HW, HR and r-ANP in Group-C2 (1.14+/-0.03, 339+/-16 and 135+/-31) and Group-C20 (1.23+/-0.04, 305+/-8 and 156+/-24) were significantly lower than those in Group-V (1.36+/-0.04 g, 389+/-9 beats min(-1) and 375+/-31 pg ml(-1), respectively). The LVEDP in Group-C2 was significantly lower than that in Group-V (7.4+/-1.4 and 12.2+/-1.2 mmHg, respectively, P<0. 05). The area of myocardial fibrosis in Group-C2 was smaller than that in Group-V (12+/-1 and 31+/-2%, P<0.01). These results indicate that a low dose of carvedilol has beneficial effects on dilated cardiomyopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Carbazoles / therapeutic use*
  • Cardiomyopathy, Dilated / etiology
  • Cardiomyopathy, Dilated / pathology
  • Cardiomyopathy, Dilated / prevention & control*
  • Carvedilol
  • Disease Progression
  • Endomyocardial Fibrosis / physiopathology
  • Endomyocardial Fibrosis / prevention & control
  • Heart / drug effects
  • Hemodynamics / drug effects
  • Male
  • Myocarditis / complications*
  • Organ Size / drug effects
  • Propanolamines / therapeutic use*
  • Rats
  • Rats, Inbred Lew
  • Vasodilator Agents / therapeutic use*
  • Ventricular Function, Left

Substances

  • Carbazoles
  • Propanolamines
  • Vasodilator Agents
  • Carvedilol