Treatment of subclinical hypothyroidism reverses ischemia and prevents myocyte loss and progressive LV dysfunction in hamsters with dilated cardiomyopathy

1 Cardiovascular Research Institute-South Dakota Health Research Foundation, University of South Dakota School of Medicine and Sioux Valley Hospitals and Health Systems, and 2 Department of Internal Medicine, University of South Dakota School of Medicine, Sioux Falls, South Dakota Submitted 11 May 2005 ; accepted in final form 13 July 2005 Growing evidence suggests that thyroid dysfunction may contribute to progression of cardiac disease to heart failure. We investigated the effects of a therapeutic dose of thyroid hormones (TH) on cardiomyopathic (CM) hamsters from 4 to 6 mo of age. CM hamsters had subclinical hypothyroidism (normal thyroxine, elevated TSH). Left ventricular (LV) function was determined by echocardiography and hemodynamics. Whole tissue pathology and isolated myocyte size and number were assessed. TH treatment prevented the decline in heart rate and rate of LV pressure increase and improved LV ejection fraction. The percentage of fibrosis/necrosis in untreated 4-mo-old CM (4CM; 15.5 ± 2.2%) and 6-mo-old CM (6CM; 21.5 ± 2.4%) hamsters was pronounced and was reversed in treated CM (TCM; 11.9 ± 0.9%) hamsters. Total ventricular myocyte number was the same between 4- and 6-mo-old controls but was reduced by 30% in 4CM and 43% in 6CM hamsters. TH treatment completely prevented further loss of myocytes in TCM hamsters. Compared with age-matched controls, resting and maximum coronary blood flow was impaired in 4CM and 6CM hamsters. Blood flow was completely normalized by TH treatment. We conclude that TH treatment of CM hamsters with subclinical hypothyroidism normalized impaired coronary blood flow, which prevented the decline in LV function and loss of myocytes. thyroid hormones; remodeling; fibrosis; blood flow Address for reprint requests and other correspondence: A. M. Gerdes, Univ. of South Dakota School of Medicine, Cardiovascular Research Inst., 1100 E. 21st St., Sioux Falls, SD 57105 (e-mail: mgerdes{at}usd.edu )