Aldosterone antagonism in an inflammatory state: evidence for myocardial protection

J Renin Angiotensin Aldosterone Syst. 2006 Sep;7(3):162-7. doi: 10.3317/jraas.2006.026.

Abstract

Introduction: Chagas' disease is one of the most important causes of dilated cardiomyopathy in South and Central America. It is an inflammatory cardiomyopathy. We wanted to investigate whether it could have the same response to aldosterone antagonism as demonstrated before in other dilated cardiomyopathies.

Objective: To evaluate the role of spironolactone in myocardial remodelling in a Chagas cardiomyopathy model.

Material and methods: We studied 60 Sirius Hamsters divided into: control (C) infected (Inf) and Inf plus spironolactone (Infsp, 40 mg/kg/day) groups, for 11 months. Echocardiography with colour doppler was performed. Left ventricular end diastolic diameter (LVEDD), fractional shortening (FS) and corrected isovolumic relaxation time (IRT) were evaluated, as well as interstitial collagen volume fraction (ICVF) and myocardial inflammation.

Result: The results demonstrated that survival was improved by use of spironolactone in the chronic phase (p<0.04). Body weight (BW) was C:190 g, Inf:167 g*, Infsp:198 g (*p<0.05, compared to C and Infsp), LVEDD/BW was C:0.31, Inf: 0.35*, Infsp: 0.29 (*p<0.05, compared to C and Infsp), FS was C:38, Inf: 35.5, Infsp: 38 (with no statistical difference) and IRT was C: 23 msec, Inf: 26 msec*, Infsp: 22 msec (p<0.05, compared to C and Infsp). ICVF (%) was attenuated at LV (C: 0.34+/-0.1, Inf: 1.75+/-0.7*, Infsp: 0.95+/-0.2*; *p<0.05, p<0.05).

Conclusion: Spironolactone attenuated the myocardial remodelling in Chagas cardiomyopathy, reduced mortality during the chronic phase and reduced inflammatory infiltration.

MeSH terms

  • Aldosterone / metabolism
  • Animals
  • Cardiotonic Agents / pharmacology*
  • Chagas Cardiomyopathy / diagnostic imaging
  • Chagas Cardiomyopathy / pathology*
  • Collagen / analysis
  • Cricetinae
  • Disease Models, Animal
  • Echocardiography, Doppler, Color
  • Female
  • Mesocricetus
  • Mineralocorticoid Receptor Antagonists / pharmacology*
  • Myocardium / chemistry
  • Spironolactone / pharmacology*
  • Trypanosoma cruzi*
  • Ventricular Remodeling / drug effects*

Substances

  • Cardiotonic Agents
  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Aldosterone
  • Collagen