Myosin heavy chain synthesis is increased in a rabbit model of
heart failure.
Eble, Diane M., Jennifer D. Walker, Rupak Mukherjee, Allen M. Samarel,
and Francis G. Spinale.
Department of Surgery, Medical University of South Carolina,
Charleston, SC 29425 and The Cardiovascular Institute, Loyola
University Chicago, Maywood, Illinois 60153
APStracts 3:0425H, 1996.
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 bpm, 3
wks, 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 3-fold, and renin
activity increased 2-fold. Despite these stimuli for hypertrophy, LV
mass to body weight ratio was unchanged (1.15+/-0.07 vs. 1.25+/
-0.05g/kg). At the myocyte level, chronic VT caused myocyte
lengthening (159.6+/-1.8 vs. 121.6+/-1.4 mm, p<0.05), but a
reduction in myocyte cross-sectional area (199(6 vs. 249(7 (m2,
p<0.0001), as well as a reduced velocity of shortening
(42.6+/-1.6 vs. 74.1+/-2.8 mm/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
GAPDH), 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.
Received 16 January 1996; accepted in final form 15 August 1996.
APS Manuscript Number H33-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996