Submitted on November 2, 2007
Accepted on February 18, 2008
Benefits of long-term beta-blockade in experimental chronic aortic regurgitation
Eric Plante1, Dominic Lachance2, Serge Champetier1, Marie-Claude Drolet1, Elise Roussel1, Marie Arsenault1*, and Jacques Couet1
1 Hopital Laval Research Center, Laval University, Quebec City, Canada
2 Hopital Laval Research Center, Laval University, Quebec City, Canada; Laval University, United States
* To whom correspondence should be addressed. E-mail: marie.arsenault{at}crhl.ulaval.ca.
Objectives: To assess the long term effects of beta blockade on survival and LV remodeling in rats with aortic valve regurgitation (AR).
Background: The pharmacological management of chronic AR remains controversial. Until now, no drug has been definitively proven effective to delay the need for valve replacement or to affect morbidity and/or mortality. Our group has reported that the adrenergic system is activated in an animal model of AR and that adrenergic blockade may help maintain a normal left ventricular (LV) function. The effects of a prolonged treatment with a beta-blocker are unknown.
Methods: 40 Wistar rats with severe AR were divided in 2 groups (n=20/gr) treated or not with metoprolol (MET) 25 mg/kg/day for 1 year. LV remodeling was evaluated by echocardiography. Survival was assessed by Kaplan-Meir curves. Hearts were harvested for tissue analysis.
Results: All animals treated with MET were alive after 6 months compared with 70% of untreated animals. After 1 year, 60% of MET animals were alive vs. 35% untreated (p=0.028). All but 1 death were sudden. There were no differences in LVEF (all above 50%) or LV dimensions. LV mass tended to be lower in the MET group. There was less sub-endocardial fibrosis in this group as well as lower LV filling pressures (LVEDP). Beta adrenergic receptor ratio (
1/2) was improved.
Conclusion: A 1-year treatment with metoprolol was well tolerated. Metoprolol improved 1 year survival, minimized left ventricular hypertrophy, improved LV filling pressures, decreased LV sub-endocardial fibrosis and helped restore beta adrenergic receptor ratio.
