Benefits of long-term {beta}-blockade in experimental chronic aortic regurgitation

Groupe de Recherche sur les Valvulopathies, Centre de Recherche Hôpital Laval, Institut de Cardiologie de Québec, Université Laval, Sainte-Foy, Quebec, Canada Submitted 2 November 2007 ; accepted in final form 18 February 2008 The objective of this study was to assess the long-term effects of β-blockade on survival and left ventricular (LV) remodeling in rats with aortic valve regurgitation (AR). The pharmacological management of chronic AR remains controversial. No drug has been definitively proven 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 normal LV function. The effects of prolonged treatment with a β-blocker are unknown. Forty Wistar rats with severe AR were divided into 2 groups of 20 animals each and treated with metoprolol (Met, 25 mg·kg –1 ·day –1 ) or left untreated for 1 yr. LV remodeling was evaluated by echocardiography. Survival was assessed by Kaplan-Meir curves. Hearts were harvested for tissue analysis. All Met-treated animals were alive after 6 mo vs. 70% of untreated animals. After 1 yr, 60% of Met-treated animals were alive vs. 35% of untreated animals ( P = 0.028). All deaths, except one, were sudden. There were no differences in LV ejection fraction (all >50%) or LV dimensions. LV mass tended to be lower in the Met-treated group. There was less subendocardial fibrosis in this group, as well as lower LV filling pressures (LV end-diastolic pressure). β-Adrenergic receptor ratio (β 1 /β 2 ) was improved. One year of treatment with Met was well tolerated. Met improved 1-yr survival, minimized LV hypertrophy, improved LV filling pressures, decreased LV subendocardial fibrosis, and helped restore the β-adrenergic receptor ratio. aortic valve regurgitation; volume overload; β-blockers; adrenergic system Address for reprint requests and other correspondence: M. Arsenault or J. Couet, Institut de Cardiologie de Québec, 2725 chemin Sainte-Foy, Sainte-Foy, (Quebec), Canada G1V 4G5 (e-mail: marie.arsenault{at}crhl.ulaval.ca )