(Circulation. 1995;91:794-801.)
© 1995 American Heart Association, Inc.
Articles |
Left Ventricular Performance and Remodeling in Rabbits After Myocardial Infarction
Effects of a Thyroid Hormone Analogue
From the Department of Internal Medicine, Veterans Administration Medical Center; and the University Heart Center, University of Arizona, Tucson, Ariz.
Correspondence to Dr Thomas E. Raya, Cardiology Section, 111C, Tucson Veterans Administration Medical Center, Tucson, AZ 85723.
Background Because the rat postinfarction model differs from human heart failure with respect to the composition of myosin heavy chain (MHC) isoforms and other contractile proteins, alternative animal models are needed for the development of new treatments for human heart failure. The purpose of this study was threefold: (1) to test the feasibility of using the V3(ß,ß) rabbit postinfarction model for the study of heart failure by characterizing the effects of chronic coronary artery occlusion on the left ventricle; (2) to determine whether the thyroid hormone analogue 3,5-diiodothyropropionic acid (DITPA) produces improvements in left ventricular function; and (3) to determine the effects of myocardial infarction and treatment with DITPA on MHC protein isoforms.
Methods and Results Male New Zealand White rabbits underwent
proximal circumflex coronary artery ligation. After infarction, rabbits
were treated with DITPA (3.75 mg/kg body wt) or placebo for 21 days and
then underwent conscious and open-chest hemodynamic studies. In
separate groups of rabbits, ß- and 
-MHC isoforms were separated,
and relative proportions were measured using gradient sodium dodecyl
sulfate–polyacrylamide gel electrophoresis and laser densitometry.
Infarction resulted in increased left ventricular
end-diastolic pressure and prolonged left ventricular
relaxation (
) (P=.001 for both variables). Postinfarction
treatment with DITPA decreased left ventricular
end-diastolic pressure and (P=.002 and
P=.001, respectively) and increased maximum positive and
negative dP/dt (P=.002 and P=.016,
respectively).
Infarcted rabbits treated with DITPA had no significant changes in
heart rate or left ventricular systolic pressure compared with
untreated rabbits with infarction. There were no significant
differences in heart rate, positive dP/dt, peak systolic pressure, or
between sham-operated rabbits and sham-operated rabbits treated
with DITPA. Although infarction resulted in increased left ventricular
diameter, there were no effects of DITPA on left ventricular
remodeling. Neither myocardial infarction nor treatment with DITPA
altered the ratio of MHC isoforms.
Conclusions Rabbits that survive occlusion of the circumflex artery will develop myocardial dysfunction and left ventricular remodeling. Therapy with DITPA, a thyroid hormone analogue, produces improvement in ventricular performance and reduces end-diastolic pressure. The hemodynamic effects of DITPA were not associated with alterations of MHC isoforms. Whether DITPA represents the prototype of a previously undescribed class of agents for the treatment of heart failure will need to be determined by clinical trials.
Key Words: 3,5-diiodothyropropionic acid • heart failure • thyroid • ventricles
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