Thyroid hormones induce unique and potentially beneficial changes in cardiac myocyte shape in hypertensive rats near heart failure

1 Cardiovascular Research Institute, University of South Dakota School of Medicine and Sioux Valley Hospitals and Health Systems, Sioux Falls, South Dakota; and 2 College of Pharmacy, Florida A&M University, Tallahassee, Florida Submitted 30 September 2004 ; accepted in final form 14 December 2004 We examined the effects of thyroid hormones (THs) on left ventricular (LV) function and myocyte remodeling in rats with spontaneously hypertensive heart failure (SHHF). SHHF rats were treated with three different TH doses from 20–21 mo of age. In terminal experiments, LV function (as determined by echocardiography and catheterization) and isolated myocyte shape were examined in SHHF rat groups and age-matched Wistar-Furth control animals. Compared with Wistar-Furth rats, the ratio of - to -myosin was reduced in untreated SHHF rats. The -to- -myosin ratio increased in all TH groups, which suggests a reversal of the fetal gene program. Low-dose TH produced no changes in LV myocyte size or function, but high-dose TH produced signs of hyperthyroidism (e.g., increased heart weight, tachycardia). The chamber diameter-to-wall thickness ratio declined with increasing dose due to reduced chamber diameter and increased wall thickness. This resulted in a 38% reduction in LV systolic wall stress in the middle- and high-dose groups despite sustained hypertension. Isolated myocyte data indicated that chamber remodeling and reduced wall stress were due to a unique alteration in myocyte transverse shape (e.g., reduced major diameter and increased minor diameter). Based on our present understanding of ventricular remodeling and wall stress, we believe these changes are likely beneficial. Results suggest that TH may be an important regulator of myocyte transverse shape in heart disease. shape; ventricular remodeling; wall stress; myosin ratio Address for reprint requests and other correspondence: A. M. Gerdes, Cardiovascular Research Institute, USD School of Medicine, 1100 East 21st St., 7th Floor, Sioux Falls, SD 57105 (E-mail: mgerdes{at}usd.edu )