MECHANISMS OF CARDIAC-HYPERTROPHY IN CANINE VOLUME OVERLOAD

This study tested whether the modest hypertrophy that develops in dogs in response to mitral regurgitation is due to a relatively small chan ge in the rate of protein synthesis or, alternatively, is due to a dec reased rate of protein degradation. After 3 mo of severe experimental mitral regurgitation, the left ventricular (LV) mass-to-body weight ra tio increased by 23% compared with baseline values. This increase in L V mass occurred with a small, but not statistically significant, incre ase in the fractional rate of myosin heavy chain (MHC) synthesis (K-s) , as measured using continuous infusion with [H-3]leucine in dogs at 2 wk, 4 wk, and 3 mo after creation of severe mitral regurgitation. Tra nslational efficiency was unaffected by mitral regurgitation as measur ed by the distribution of MHC mRNA in polysome gradients. Furthermore, there was no detectable increase in translational capacity as measure d by either total RNA content or the rate of ribosome formation. These data indicate that translational mechanisms that accelerate the rate of cardiac protein synthesis are not responsive to the stimulus of mit ral regurgitation. Most of the growth after mitral regurgitation was a ccounted for by a decrease in the fractional rate of protein degradati on, calculated by subtracting fractional rates of protein accumulation at each time point from the corresponding K-s values. We conclude tha t 1) volume overload produced by severe mitral regurgitation does not trigger substantial increases in the rate of protein synthesis and 2) the modest increase in LV mass results primarily from a decrease in th e rate of protein degradation.