Aldosterone antagonism in an inflammatory state: evidence for myocardial protection.
BACKGROUND
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.


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.


RESULTS
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).


CONCLUSIONS
Spironolactone attenuated the myocardial remodelling in Chagas cardiomyopathy, reduced mortality during the chronic phase and reduced inflammatory infiltration.
Ramires
Felix J A
FJ
Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil. carfelix@incor.usp.br
Salemi
Vera M C
VM
Ianni
Barbara M
BM
Fernandes
Fábio
F
Martins
Daniel G
DG
Billate
Angelina
A
Neto
Edécio Cunha
EC
Mady
Charles
C
D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002598:Chagas Cardiomyopathy / Q000000981:diagnostic imaging / Q000473:pathology*; D003094:Collagen / Q000032:analysis; D006224:Cricetinae; D004195:Disease Models, Animal; D018618:Echocardiography, Doppler, Color; D005260:Female; D008647:Mesocricetus; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009206:Myocardium / Q000737:chemistry; D013148:Spironolactone / Q000494:pharmacology*; D014349:Trypanosoma cruzi; D020257:Ventricular Remodeling / Q000187:drug effects*
D002316:Cardiotonic Agents; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone; D003094:Collagen