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1Cardiovascular Research Center, Sanford Research/University of South Dakota; 2Metabolism and Nutrition Research Center, Sanford Research/University of South Dakota, Sioux Falls, South Dakota; 3Endocrinology, Instituto de Investigaciones Biomédicas Alberto Sols, Autonomous University of Madrid and Spanish Research Council, Madrid, Spain
Submitted 29 November 2007 ; accepted in final form 26 February 2008
The link between thyroid dysfunction and cardiovascular diseases has been recognized for more than 100 years. Although overt hypothyroidism leads to impaired cardiac function and possibly heart failure, the cardiovascular consequences of borderline low thyroid function are not clear. Establishment of a suitable animal model would be helpful. In this study, we characterized a rat model to study the relationship between cardiovascular function and graded levels of thyroid activity. We used rats with surgical thyroidectomy and subcutaneous implantation of slow release pellets with three different T4 doses for 3 wk. In terminal experiments, cardiac function was evaluated by echocardiograms and hemodynamics. Myocardial arteriolar density was also quantified morphometrically. Thyroid hormone levels in serum and heart tissue were determined by RIA assays. Thyroidectomy alone led to cardiac atrophy, severe cardiac dysfunction, and a dramatic loss of arterioles. The low T4 dose normalized serum T3 and T4 levels, but cardiac tissue T3 and T4 remained below normal. Low-dose T4 failed to prevent cardiac atrophy or restore cardiac function and arteriolar density to normal values. All cardiac function parameters and myocardial arteriolar density were normalized with the middle dose of T4, whereas the high dose produced hyperthyroidism. Our results show that thyroid hormones are important regulators of cardiac function and myocardial arteriolar density. This animal model will be useful in studying the pathophysiological consequences of mild thyroid dysfunction. Results also suggest that cardiac function may provide valuable supplemental information in proper diagnosis of mild thyroid conditions.
thyroidectomy; thyroxine; myocardial arterioles
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