Abstract 2335: Beta-blockade Improves Survival in Chronic Aortic Regurgitation in Rats
Introduction: Chronic aortic valve regurgitation (AR) leads to progressive left ventricular eccentric hypertrophy and eventually heart failure. Current treatment strategies based on vasodilator therapy are not very effective. We have previously shown in a rat model of this disease that a 6-month treatment with oral metoprolol (25/mg/kg/d) significantly improved left ventricular function and slowed the development of eccentric hypertrophy. However, the effects of chronic metoprolol treatment on survival have never been evaluated in this animal model. Hypothesis: We assessed the hypothesis that long term treatment with beta-blocker metoprolol in rats with chronic AR would have beneficial effects on the survival.
Methods: Sixty adult Wistar male rats were randomly assigned to 3 groups (n=20/gr): 1, untreated animals with AR; 2, AR treated with metoprolol (25 mg/kg/d) in drinking water and 3, sham-operated animals. Severe AR was induced in anaesthetised rats by puncturing the aortic valve leaflets with a catheter via a retrograde approach from the right carotid artery. AR severity was assessed semi-quantitatively by echocardiography. Only animals with severe AR were included.
Results: All AR rats had similar severity of regurgitation as evaluated by echocardiography. After 6 months, LV dilatation was similar in Gr.1 and Gr.2. EF was better in animals treated with metoprolol but was above 50% in untreated animals. All deaths except one were sudden and not preceded by any overt sign or symptom of heart failure. Only 1 death was attributed to heart failure. Results are summarized below.
Conclusion: In rats with severe chronic aortic valve regurgitation, metoprolol treatment improved survival. Mortality in rats with chronic AR was mostly attributable to sudden death. A survival benefit was evident in animals treated with metoprolol despite similar levels of LV dilatation in treated vs. untreated animals and that EF was still above 50% in untreated animals.