Low thyroid function leads to cardiac atrophy with chamber dilatation, impaired myocardial blood flow, loss of arterioles, and severe systolic dysfunction

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 alpha-myosin heavy chain were reduced in hypothyroidism, whereas phospholamban and alpha-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.