Myosin heavy chain synthesis during the progression of chronic tachycardia induced heart failure in rabbits.

Chronic tachycardia causes LV dilatation and dysfunction, with no hypertrophy. However, the contributing mechanisms responsible for the left ventricular (LV) remodeling in the absence of myocardial growth in this model of heart failure remain unclear. Therefore, the goal of the present study was to serially examine changes in LV function, steady state myosin heavy chain (MHC) mRNA levels, in vivo synthesis rates, and abundance with the progression of chronic tachycardia induced heart failure. Adult rabbits (3.5-4.5 kg) were studied after one, two, or three weeks of pacing ventricular tachycardia (VT; 400 bpm) and in controls (n = 6 for all groups). LV fractional shortening was reduced by 30% at week one and by over 50% at week three of chronic VT. End-diastolic dimension (EDD) increased at week two compared to controls (1.66 +/- 0.10 vs 1.35 +/- 0.11 cm, p < 0.05) and increased further at week three of VT (1.70 +/- 0.06 cm, p < 0.05). The progressive changes in LV geometry and function with chronic VT were not associated with concomitant time dependent changes in LV mass or MHC mRNA levels. In contrast, MHC fractional synthesis rates increased and reached statistical significance at week three of VT compared to controls (8.3 +/- 0.8 vs 5.5 +/- 0.5%/day, p < 0.05). Despite the stable or increased MHC protein synthesis rates, there was no change in MHC protein abundance at any point during the progression of VT induced heart failure, implicating enhanced MHC protein degradation. Thus, this study demonstrated that a contributory mechanism for the LV remodeling and lack of myocardial growth, which occurs with VT induced heart failure, is enhanced contractile protein degradative processes.