Chronic ventricular tachycardia (chronic VT) causes left ventricular (LV) dysfunction and is associated with increased LV wall stress and neurohormonal activation, but no LV hypertrophy. The mechanisms responsible for the lack of myocardial growth with chronic VT are unknown. Accordingly, this study examined contractile protein [myosin heavy chain (MHC)] synthesis in a rabbit model of chronic VT. MHC mRNA levels, protein concentration, and synthesis rates were examined in control rabbits (n = 18) and in rabbits with chronic VT (400 beats/min, 3 wk, n = 18). With chronic VT, LV end-diastolic volume increased (8.2 +/- 0.8 vs. 5.3 +/- 0.6 ml, P < 0.05), ejection fraction decreased (12 +/- 3 vs. 38 +/- 4%, P < 0.05) and peak systolic wall stress increased (963 +/- 93 vs. 262 +/- 42 g/cm2, P < 0.05). Plasma catecholamine and endothelin levels also increased threefold, and renin activity increased twofold. Despite these stimuli for hypertrophy, LV mass-to-body weight ratio was unchanged (1.15 +/- 0.07 vs. 1.25 +/- 0.05 g/kg). At the myocyte level, chronic VT caused myocyte lengthening (159.6 +/- 1.8 vs. 121.6 +/- 1.4 microm, P < 0.05), but a reduction in myocyte cross-sectional area (199 +/- 6 vs. 249 +/- 7 microm2, P < 0.0001), as well as a reduced velocity of shortening (42.6 +/- 1.6 vs. 74.1 +/- 2.8 microm/s, P < 0.05). Chronic VT resulted in a significant increase in the rate of MHC synthesis, but paradoxically, there was no change in LV MHC content. Despite increased MHC synthesis, relative levels of MHC mRNA were not increased in chronic VT (2.79 +/- 0.23 vs. 2.44 +/- 0.20 AU, relative to glyceraldehyde-3-phosphate dehydrogenase), suggesting an increase in MHC translational efficiency. These unique findings suggest accelerated degradative processes must contribute to the failure of myocardial growth in this model of LV dysfunction in which increased LV wall stress, neurohormonal activation, and increased protein synthesis occurred.