Effects of canrenone on myocardial reactive fibrosis in a rat model of postinfarction heart failure.
BACKGROUND
Spironolactone reduces overall mortality by 30% in advanced congestive heart failure. Nevertheless, few data are available with regard to the effects of mineral corticoid inhibition in postinfarction heart failure.


METHODS
Experimental myocardial infarction was induced by left coronary ligation in 70 male rats with body weights ranging from 180 to 200 gr. The day after surgery, animals were randomized to either placebo or canrenone-gamma-cyclodestrin 8 mg/kg/die or canrenone-gamma-cyclodestrin 18 mg/kg/die. Twelve animals served as the control group. After two weeks, the rats underwent closed chest left ventricular catheterization. The heart was the rapidly excised for subsequent histological analysis.


RESULTS
Compared with controls, infarcted rats had reduced left ventricular systolic pressures (-6%) and higher left ventricular end-diastolic pressures (+600%), associated with a marked increase of mean collagen fraction (+446%) and perivascular fibrosis (+72%). Compared with placebo-infarcted rats, in the group treated with high canrenone dose there was a significant reduction of left ventricular systolic and end-diastolic pressures (-6.5% and -23%, respectively) and an attenuation of interstitial and perivascular fibrosis (-47% and -34%, respectively). The low-dose canrenone group did not show differences compared with the placebo infarcted rats, except for a slight reduction of mean collagen fraction (-21%).


CONCLUSIONS
Canrenone attenuates LV interstitial remodeling and reduces filling pressures in rats with postinfarction heart failure.
Cittadini
Antonio
A
Department of Internal Medicine and Cardiovascular Sciences, University Federico II, Via Sergio Pansini 5, 80131 Naples, Italy. cittadin@unina.it
Casaburi
Cosma
C
Monti
Maria Gaia
MG
Di Gianni
Angela
A
Serpico
Raffaella
R
Scherillo
Giovanna
G
Saldamarco
Lavinia
L
Vanasia
Massimo
M
Saccà
Luigi
L
D000284:Administration, Oral; D000450:Aldosterone / Q000097:blood / Q000378:metabolism; D000818:Animals; D002192:Canrenone / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism; D003505:Cyclodextrins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004719:Endomyocardial Fibrosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D006333:Heart Failure / Q000209:etiology / Q000401:mortality / Q000473:pathology*; D006439:Hemodynamics; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects; D047408:gamma-Cyclodextrins
D003505:Cyclodextrins; D000451:Mineralocorticoid Receptor Antagonists; D047408:gamma-Cyclodextrins; D000450:Aldosterone; D002192:Canrenone; D003094:Collagen; C023792:gamma-cyclodextrin; D006909:Hydroxyproline