Direct effects of 3 combinations of enalapril, metoprolol, and spironolactone on cardiac remodeling in dilated cardiomyopathic hamsters.
BACKGROUND
In congestive heart failure, enalapril (E), metoprolol (M), and spironolactone (S) improve survival. Their direct effects on cardiac remodeling, when administered in combination, remain to be assessed.


RESULTS
One hundred and five cardiomyopathic hamsters were divided into 5 groups (control, E, E-M, E-S, E-M-S) and treated from 150 to 240 days of age (E: 3 mg/kg, M: 1 mg/kg, S: 20 mg/kg). Cardiac and systemic hemodynamics, and cardiac remodeling were investigated. There was no difference between groups on blood pressure. Compared with C, both S-treated groups significantly increased cardiac index (E-S: +49%; E-M-S: +46%). Compared with C, E significantly decreased left ventricular (LV) cavity area (-10%). Compared with E, all combinations significantly decreased LV cavity area (E-M: -13%, E-S: -22%, E-M-S: -19%) and right ventricular (RV) collagen density (E-M: -18%, E-S: -30%, E-M-S: -34%), and the tri-therapy significantly decreased LV collagen density (-18%). Compared with bi-therapies, the tri-therapy significantly decreased LV (-19% vs. E-M, -16% vs. E-S) and RV (-20% vs. E-M) collagen densities.


CONCLUSIONS
At subdepressor doses, both bi-therapies induced similar effects on myocardial remodeling, enhancing the effects of E on LV cavity area and reducing RV collagen density. Compared with bi-therapies, the tri-therapy induced additional effects on LV and RV collagen densities.
Laviolle
Bruno
B
Laboratoire de Pharmacologie Expérimentale et Clinique, UPRES EA 3194 Groupe de Recherche Cardio-Vasculaire, Faculté de Médecine, Rennes, France.
Pape
Danielle
D
Turlin
Bruno
B
Bellissant
Eric
E
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D006224:Cricetinae; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D009206:Myocardium / Q000473:pathology; D013148:Spironolactone / Q000627:therapeutic use*; D020257:Ventricular Remodeling / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D004656:Enalapril; D008790:Metoprolol