MYOSIN HEAVY-CHAIN SYNTHESIS DURING THE PROGRESSION OF CHRONIC TACHYCARDIA-INDUCED HEART-FAILURE IN RABBITS

Chronic tachycardia causes LV dilatation and dysfunction, with no hype rtrophy. However, the contributing mechanisms responsible for the left ventricular (LV) remodeling in the absence of myocardial growth in th is model of heart failure remain unclear. Therefore, the goal of the p resent study was to serially examine changes in LV function, steady st ate myosin heavy chain (MHC) mRNA levels, in vivo synthesis rates, and abundance with the progression of chronic tachycardia induced heart f ailure. Adult rabbits (3.5-4.5 kg) were studied after one, two, or thr ee weeks of pacing ventricular tachycardia (VT; 400 bpm) and in contro ls (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-diasto lic 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 t hree 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 concom itant time dependent changes in LV mass or MHC mRNA levels. In contras t, MHC fractional synthesis rates increased and reached statistical si gnificance 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 protei n 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 contra ctile protein degradative processes.