Effects Of Thyroxine On Expression Of Peripheral Lymphocyte β-adrenoceptors In Patients With Congestive Heart Failure

OBJECTIVE Thyroid hormone metabolism is frequently altered in advanced congestive heart failure (CHF). Triiodothyronine (T3) levels are low and reverse T3 levels high in most patients, with thyroxine (T4) and thyroid-stimulating hormone (TSH) levels remaining normal, which had been described as euthyroid sick syndrome, even in the most critically ill patients. Hypothroxinemia is associated with poor hemodynamics and low serum sodium and is an independent predictor of poor survival. Because the poor prognosis was associated with low thyroid hormone (TH) levels, several researchers wondered if supplementation by T3 could improve clinical outcomes. There is a down-regulation of 3 -adrenoceptors ( ?-AR) in cardiomyocytes in animal models and patients with CHF, which is one reason of difficult treatment. The purpose of present study is to determine whether the TH improves cardiac function and lymphocyte 3 -AR density in CHF patients, and explores their possible mechanisms.Materials and Methods 28 patients with NYFIA class III or IV advanced CHF due to dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM) were randomly divided into observation group and control group. Low-dose L-thyroxine (L-T50) was added in the observation group. Exercise tolerance, chest X-ray, and echocardiographic parameters were obtained before and after one or threemonths of treatment. Before and after one month of treatment, Ficoll-Hyperque liquid was used to separate peripheral lymphocytes, 125I-Pindolol radioligand banding was used to measure ?- adrenoceptors in peripheral lymphocytes. RT-PCR was used to measure ?1 - adrenoceptors expression in peripheral lymphocytes.Results L-T50 therapy improved cardiac output (CO, 2.98 ?.31 vs 3.24 ?.28 L/min, PO.01) left ventricular ejection fraction (LVEF, 26.21% ?3.21% vs 37.93% ?9.01%, P.01), and decreased the,01 isovolumetric relaxation time (IVRT, 0.12 + 0.04 vs 0.10 + 0.02, PO.01). The maximal number of banding sites (3 max) in peripheral lymphocytes and the serum TH in patients with CHF was lower than that in normal health people, L-T50 administration induced a up-regulation of ?-AR expression in peripheral lymphocytes surface. L-T50 was well tolerated without episodes of ischemia or arrhythmia. There was no significantly change in heart rate or metabolic rate.Conclusion Low-dose TH administered for three months significantly improved the clinical manifestations and cardiac function, and also brought a cardiac structure remodeling, which may be benefit to advanced CHF patients. The density of ?adrenoceptors of lymphocytes in patients with CHF due to ICM or DCM was lower than that in normal health people, thyroxine administration induced a ?-adrenoceptors up-regulation in peripharal lymphocytes surface, which may be due to improvement of ?- adrenoceptors expression.