Abstract 3448: Reversal of Left Ventricular Pressure-Overload Hypertrophy Prevents Apoptotic Cardiomyocyte Loss in Severe Hypertrophy
Objective: Cardiac hypertrophy from pressure overload is an adaptive response which if unrelieved leads to heart failure. A major contributing factor to failure is continuous cardiomyocyte loss due to apoptosis during progressive hypertrophy. The optimal timing of surgery for relief of the pressure load in order to preserve cardiomyocyte viability and maintain contractile function is unknown. In this study we sought to determine whether removing the pressure overload on the LV at different stages of hypertrophy prevents cardiomyocyte loss and determines long-term outcome of contractile function.
Methods: Newborn rabbits underwent banding of the descending aorta. Surgical removal of the band was performed at two different time points during hypertrophy; Group 1 (n=5): early hypertrophy (4wks of age) with low levels of apoptotic cell loss (3±0.4TPC/N) and Group 2 (n=3): peak hypertrophy (6wks of age) at onset of continuous apoptotic cell loss (10±2TPC/N). Complete relief of the aortic constriction was determined by measuring upper and lower limb blood pressure and post-mortem morphologic analysis of the aorta. Cardiac function (%SF=shortening fraction) and Mass/ Volume-ratio (M/V=index of remodeling) was monitored by weekly transthoracic echocardi-ography. Data are expressed as mean±SEM. P<0.05 was considered significant.
Results: By 8wks of age 33% of the banded animals had died but all animals with band removal were alive. Apoptosis at 12wks of age for group 1 (3±0.7TPC/N) and group 2 (4±1TPC/N) was significantly decreased compared to pre band removal. *p<0.05 vs. early hyp., group 1 and 2.#p<0.05 vs. group 1 and 2.**all animals dead.
Conclusions: These results demonstrate that removal of the aortic constriction prior to significant cumulative cardiomyocyte loss from apoptosis leads to reversal of hypertrophy, maintenance of cardiomyocyte viability and contractile function, implicating apoptosis as a major mechanism of failure from pressure overload.