Medium-term effectiveness of L-thyroxine treatment in idiopathic dilated cardiomyopathy

Moruzzi, P; Doria, Elisabetta; Agostoni, Piergiuseppe

doi:10.1016/s0002-9343(96)00281-1

Cited by 128 publications

(82 citation statements)

References 21 publications

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“…Cardiac failure was shown to be associated with both a decline in circulating TH levels (11,17) and altered cardiac TH signaling, as evidenced by changes in myocardial expression of TH nuclear receptor isoforms (15,16). The observation that short-term TH administration improves cardiac performance, both in animal models (2, 23) of cardiac dysfunction and in patients (11,17,22) suffering from cardiac failure, agrees with this notion. At this time, our understanding of the temporal adaptive response to TH supplementation in heart disease is very limited.…”

mentioning

confidence: 65%

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

Khalife

Tang

Kuzman

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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. Treatment of subclinical hypothyroidism reverses ischemia and prevents myocyte loss and progressive LV dysfunction in hamsters with dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 289: H2409 -H2415, 2005. First published July 15, 2005; doi:10.1152/ajpheart.00483.2005.-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 Ϯ 2.2%) and 6-mo-old CM (6CM; 21.5 Ϯ 2.4%) hamsters was pronounced and was reversed in treated CM (TCM; 11.9 Ϯ 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 agematched 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 THE EFFECTS OF THYROID HORMONES (TH) on the cardiovascular system have been well studied. It is clear that both hypothyroidism and hyperthyroidism can lead to deleterious changes in cardiovascular function. Decreased TH levels have been reported in a variety of nonthyroidal illnesses (18), including congestive heart failure (12) and myocardial infarction (6). The decrease in TH levels also appears to be related to the severity of heart failure (12). This is not a minor point, because low 3,5,3'-triiodothyronine (T 3 ) concentrations are a strong, independent predictive marker of poor prognosis in cardiac patients and might represent a determining factor directly implicated in the evolution and prognosis of these conditions (14). Growing evidence also suggests that subclinical thyroid dysfunction might play an important role in heart failure (10, 21). This is highly relevant from a clinical standpoint because this patient group does not typically receive TH treatment.Development of heart failure is accompanied by a variety of neuroendocrine changes. Cardiac failure was shown to be associated with both a decline in circulating TH levels (11,17) and altered cardiac TH signaling, as evidenced by changes in myocardial expression of TH nuclear receptor isoforms (15,16). The observation that short-term TH administration improves cardiac performance, both in anim...

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confidence: 65%

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

Khalife

Tang

Kuzman

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…Furthermore, it provides an explanation for the observed increased mortality in patients with cardiac dysfunction and low circulating TH (30) and for the beneficial effect of TH treatment in heart failure (31,32). It should be noted that low serum T 3 with unchanged T 4 , known as non-thyroidal illness (NTI), occurs during various disease states and particularly in myocardial infarction and heart failure (33).…”

Section: Discussionmentioning

confidence: 99%

Time-dependent changes in the expression of thyroid hormone receptor α1 in the myocardium after acute myocardial infarction: possible implications in cardiac remodelling

et al. 2007

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The present study investigated whether changes in thyroid hormone (TH) signalling can occur after acute myocardial infarction (AMI) with possible physiological consequences on myocardial performance. TH may regulate several genes encoding important structural and regulatory proteins particularly through the TRa1 receptor which is predominant in the myocardium. AMI was induced in rats by ligating the left coronary artery while sham-operated animals served as controls. This resulted in impaired cardiac function in AMI animals after 2 and 13 weeks accompanied by a shift in myosin isoforms expression towards a fetal phenotype in the non-infarcted area. Cardiac hypertrophy was evident in AMI hearts after 13 weeks but not at 2 weeks. This response was associated with a differential pattern of TH changes at 2 and 13 weeks; T 3 and T 4 levels in plasma were not changed at 2 weeks but T 3 was significantly lower and T 4 remained unchanged at 13 weeks. A twofold increase in TRa1 expression was observed after 13 weeks in the non-infarcted area, P!0.05 versus sham operated, while TRa1 expression remained unchanged at 2 weeks. A 2.2-fold decrease in TRb1 expression was found in the non-infarcted area at 13 weeks, P!0.05, while no change in TRb1 expression was seen at 2 weeks. Parallel studies with neonatal cardiomyocytes showed that phenylephrine (PE) administration resulted in 4.5-fold increase in the expression of TRa1 and 1.6-fold decrease in TRb1 expression versus untreated, P!0.05. In conclusion, cardiac dysfunction which occurs at late stages after AMI is associated with increased expression of TRa1 receptor and lower circulating tri-iodothyronine levels. Thus, apo-TRa1 receptor state may prevail contributing to cardiac fetal phenotype. Furthermore, down-regulation of TRb1 also contributes to fetal phenotypic changes. a1-adrenergic signalling is, at least in part, involved in this response. 156 415-424 European Journal of Endocrinology

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“…Whether or not this condition should be treated remains a matter of debate (Klemperer et al 1995, Utiger 1995, Camacho & Dwarkanathan 1999. However, during the past 5-10 years, clinical studies have explored the possibility of improving heart function using treatment with T 3 or T 4 (Moruzzi et al 1996, Chowdhury et al 1999, Mullis-Jansson et al 1999, both in children with congenital heart disease and in elderly patients with congestive heart failure. To date, the thyroid hormone analog, diiodothyropropionic acid (DITPA), which possibly has a greater effect on cardiac contractility than on frequency, has been applied in animal studies (Pennock et al 1993, Morkin et al 1996, Spooner et al 1999.…”

Section: Introductionmentioning

confidence: 99%

Uptake of triiodothyronine and triiodothyroacetic acid in neonatal rat cardiomyocytes: effects of metabolites and analogs

Verhoeven¹,

Putten²,

Hennemann³

et al. 2002

Journal of Endocrinology

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Cellular and nuclear uptake of [125 I]tri-iodothyronine (T 3 ) and [125 I]triiodothyroacetic acid (Triac) were compared in cardiomyocytes of 2-3 day old rats, and the effect of thyroid hormone analogs on cellular T 3 uptake was measured. Cells (5-10 10 5 per well) were cultured in DMEM-M199 with 5% horse serum and 5% FCS. Incubations were performed for from 15 min to 24 h at 37 C in the same medium, 0·5% BSA and [125 I]T 3 (100 pM), or [ 125 I]Triac (240 pM). Expressed as % dose, T 3 uptake was five times Triac uptake, but expressed as fmol/pM free hormone, Triac uptake was at least 30% (P<0·001) greater than T 3 uptake, whereas the relative nuclear binding of the two tracers was comparable. The 15 min uptake of [ 125

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Medium-term effectiveness of L-thyroxine treatment in idiopathic dilated cardiomyopathy

Cited by 128 publications

References 21 publications

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

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

Time-dependent changes in the expression of thyroid hormone receptor α1 in the myocardium after acute myocardial infarction: possible implications in cardiac remodelling

Uptake of triiodothyronine and triiodothyroacetic acid in neonatal rat cardiomyocytes: effects of metabolites and analogs

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