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(Circulation. 2005;112:3122-3130.)
© 2005 American Heart Association, Inc.

Heart Failure

Low Thyroid Function Leads to Cardiac Atrophy With Chamber Dilatation, Impaired Myocardial Blood Flow, Loss of Arterioles, and Severe Systolic Dysfunction

Yi-Da Tang, MD, PhD; James A. Kuzman, PhD; Suleman Said, MS; Brent E. Anderson, BS; Xuejun Wang, MD, PhD; A. Martin Gerdes, PhD

From the Cardiovascular Research Institute-South Dakota Health Research Foundation (Y.-D.T., J.A.K., S.S., B.E.A., X.W., A.M.G.), University of South Dakota School of Medicine and Sioux Valley Hospitals and Health Systems, and Department of Internal Medicine (A.M.G.), University of South Dakota, Sioux Falls, SD.

Correspondence to A. Martin Gerdes, PhD, University of South Dakota School of Medicine, Cardiovascular Research Institute, 1100 E 21st St, Suite 700, Sioux Falls, SD 57105. E-mail mgerdes{at}usd.edu

Received May 7, 2005; de novo received July 1, 2005; revision received August 19, 2005; accepted August 26, 2005.

Background— Although thyroid dysfunction has been linked to heart failure, it is not clear whether hypothyroidism alone can cause heart failure.

Methods and Results— Hypothyroidism was induced in adult rats by treatment with 0.025% propylthiouracil (PTU) for 6 weeks (PTU-S) and 1 year (PTU-L). Echocardiographic measurements, left ventricular (LV) hemodynamics, isolated myocyte length (KOH method), myocardial blood flow (fluorescent microspheres), arteriolar morphometry, and gene expression (Western blot) were determined. Heart weight, heart rate, LV systolic blood pressure, LV ejection fraction, LV fractional shortening, and systolic wall thickness were reduced in PTU-S and PTU-L rats. LV internal diameter in systole increased by 40% in PTU-S and 86% in PTU-L. LV internal dimension in diastole was increased in PTU-S and PTU-L rats, but only PTU-L rats showed a significant increase in myocyte length due to series sarcomere addition. Resting and maximum (adenosine) myocardial blood flow were reduced in both PTU-S and PTU-L rats. Impaired blood flow was due to a large reduction in arteriolar length density and small arterioles in PTU-S and PTU-L (P<0.05 or greater for all of the above comparisons). Expression of sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase (SERCA)-2a and -myosin heavy chain were reduced in hypothyroidism, whereas phospholamban and ß-myosin heavy chain were increased.

Conclusions— Hypothyroidism led to severe, progressive systolic dysfunction and increased chamber diameter/wall thickness ratio despite a reduction in cardiac mass. Chamber dilatation in PTU-L rats was due to series sarcomere addition, typical of heart failure. Hypothyroidism resulted in impaired myocardial blood flow due to a dramatic loss of arterioles. Thus, we have identified 2 important new mechanisms by which low thyroid function may lead to heart failure.

Key Words: heart failure • hormones • myocytes • pathology • remodeling

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