Effects of canrenone on myocardial reactive fibrosis in a rat model of postinfarction heart failure.

Abstract

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.

MATERIALS AND 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.

• Authors: Antonio Cittadini, Cosma Casaburi, Maria Gaia Monti, Angela Di Gianni, Raffaella Serpico, Giovanna Scherillo, Lavinia Saldamarco, Massimo Vanasia, Luigi Saccà
• Journal: Cardiovascular drugs and therapy (Cardiovasc Drugs Ther) Vol. 16 Issue 3 Pg. 195-201 (May 2002) ISSN: 0920-3206 [Print] United States
• PMID: 12374896 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Cyclodextrins
• Mineralocorticoid Receptor Antagonists
• gamma-Cyclodextrins
• Aldosterone
• Canrenone
• Collagen
• gamma-cyclodextrin
• Hydroxyproline

Topics

• Administration, Oral
• Aldosterone (blood, metabolism)
• Animals
• Canrenone (chemistry, pharmacology, therapeutic use)
• Collagen (metabolism)
• Cyclodextrins (chemistry, pharmacology, therapeutic use)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Endomyocardial Fibrosis (drug therapy, etiology, pathology)
• Heart Failure (etiology, mortality, pathology)
• Hemodynamics
• Hydroxyproline (metabolism)
• Male
• Mineralocorticoid Receptor Antagonists (pharmacology, therapeutic use)
• Myocardial Infarction (complications, pathology)
• Myocardium (metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• Ventricular Function, Left (drug effects)
• gamma-Cyclodextrins