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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyroid hormone has unique actions that make it a novel and possibly useful agent for treatment of heart failure. Because of potential adverse effects of thyroid hormone, however, there has been interest in developing analogues with fewer undesirable side effects. Screening of compounds structurally related to levothyroxine identified 3,5-diiodothyropropionic acid (DITPA) as an analogue with inotropic selectivity and low metabolic activity in hypothyroid rats. When DITPA was administered alone or in combination with captopril in rat and rabbit postinfarction models of heart failure, cardiac output was increased and left ventricular end-diastolic pressure (LV EDP) was decreased without increasing heart rate. A pilot clinical study was undertaken to evaluate the safety and efficacy of DITPA. In a dose-ranging study in 7 normal volunteers the drug was well tolerated. A double-blind comparison then was made of DITPA versus placebo in a group of 19 patients with moderately severe heart failure. Patients were randomly assigned to receive either 1.875 mg/kg of DITPA or placebo daily. After 2 weeks the drug was increased to 3.75 mg/kg daily for an additional 2 weeks. In heart failure patients receiving the drug for 4 weeks, cardiac index was increased (p = 0.04) and systemic vascular resistance index was decreased (p = 0.02). Total serum cholesterol (p = 0.013) and triglycerides (p = 0.005) also were decreased significantly. These results indicate that DITPA is well tolerated and could represent a useful new agent for treatment of congestive heart failure.
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PMID:Clinical and experimental studies on the use of 3,5-diiodothyropropionic acid, a thyroid hormone analogue, in heart failure. 1216 18

Thyroid hormones have been shown to be absolutely necessary for early brain development. During pregnancy, both maternal and foetal thyroid hormones contribute to foetal brain development and maternal supply explains why most of the athyreotic newborns usually do not show any signs of hypothyroidism at birth. Foetal and/or neonatal hypothyroidism is a rare disorder. Its incidence, as indicated by neonatal screening, is about 1:4000. Abnormal thyroid development (i.e. agenesia, ectopic gland, hypoplasia) or inborn errors in thyroid hormone biosynthesis are the most common causes of permanent congenital hypothyroidism. Recent studies reported that mutations involving Thyroid Transcriptor Factors (TTF) such as TTF-1, TTF-2, PAX-8 play an important role in altered foetal thyroid development. Deficiency of transcriptor factor (Pit-1, Prop-1, LHX-3) both in mother and in the foetus represents another rare cause of foetal hypothyroidism. At birth clinical picture may be not always so obvious and typical signs appear only after several weeks but a delayed diagnosis could have severe consequences consisting of delayed physical and mental development. Even if substitutive therapy is promptly started some learning difficulties might still arise suggesting that intrauterine adequate levels of thyroid hormones are absolutely necessary for a normal neurological development. Placental transfer of maternal antithyroid antibodies inhibiting fetal thyroid function can cause transient hypothyroidism at birth. If the mother with thyroid autoimmune disease is also hypothyroid during pregnancy and she doesn't receive substitutive therapy, a worse neurological outcome may be expected for her foetus. Foetal and/or neonatal hyperthyroidism is a rare condition and its incidence has been estimated around 1:4000-40000, according to various authors. The most common causes are maternal thyroid autoimmune disorders, such as Graves' disease and Hashimoto's thyroiditis. Rarer non autoimmune causes recently identified are represented by TSH receptor mutations leading to constitutively activated TSH receptor. Infants born to mothers with Graves' history may develop neonatal thyrotoxicosis. Foetal/neonatal disease is due to transplacental thyrotrophin receptor stimulating antibodies (TRAb) passage. It's extremely important recognizing and treating Graves' disease in mothers as soon as possible, because a thyrotoxic state may have adverse effects on the outcome of pregnancy and both on the foetus and newborn. Thyrotoxic foetuses may develop goitre, tachycardia, hydrops associated with heart failure, growth retardation, craniosynostosis, increased foetal motility and accelerated bone maturation. Neonatal Graves' disease tends to resolve spontaneously within 3-12 weeks as maternal thyroid stimulating immunoglobulins are cleared from the circulation but subsequent development may be impaired by perceptual motor difficulties. Hashimoto's thyroiditis is a very common autoimmune thyroid disease. In presence of maternal Hashimoto's thyroiditis, there are usually no consequences on foetal thyroid, even if antiTPO and antiTg antibodies can be found in the newborn due to transplacental passage. However there are some literature reports describing foetal and neonatal hyperthyroidism in the affected mothers' offspring.
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PMID:Foetal and neonatal thyroid disorders. 1224 77

In heart failure, thyroid hormone (TH) treatment improves cardiac performance. The long-term effects of TH on cardiac function and metabolism, however, are incompletely known. To investigate the effects of up to 28 days of TH treatment, male Wistar rats received 3,3',5-triiodo-l-thyronine (200 microg/kg sc per day) leading to a 2.5-fold rise in plasma fatty acid (FA) level and progressive cardiac hypertrophy (+47% after 28 days) (P < 0.001). Ejection fraction (echocardiography) was increased (+12%; P < 0.05) between 7 and 14 days and declined thereafter. Neither cardiac FA oxidation, glycolytic capacity (homogenates) per unit muscle mass, nor mRNA levels of proteins involved in FA and glucose uptake and metabolism (Northern blots and microarray) were altered. After 28 days of treatment, mRNA levels of uncoupling proteins (UCP) 2 and 3 and atrial natriuretic factor were increased (P < 0.05). This indicates that TH-induced hypertrophy is associated with an initial increase in cardiac performance, followed by a decline in cardiac function and increased expression of UCPs and atrial natriuretic factor, suggesting that detrimental effects eventually prevail.
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PMID:Functional and metabolic adaptation of the heart to prolonged thyroid hormone treatment. 1238 19

Two Great Danes were evaluated for signs of congestive heart failure. Dilated cardiomyopathy was diagnosed in each dog. Both dogs were diagnosed concurrently with primary hypothyroidism. Following appropriate supplementation with levothyroxine, both dogs showed significant improvement in myocardial contractility, as demonstrated by increased fractional shortening and reductions in left atrial size, and left ventricular end-systolic and diastolic diameters. These observations suggest that hypothyroidism may lead to myocardial failure in Great Danes that is partially or fully reversible following thyroid hormone replacement therapy, and that hypothyroidism should be considered in all Great Danes presenting with systolic failure.
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PMID:Hypothyroidism and myocardial failure in two Great Danes. 1261 41

1. Receptor-independent activation of heterotrimeric G proteins by plasma membrane-associated nucleoside diphosphate kinase (NDPK) has been demonstrated in vivo, and elevated levels of NDPK were found in purified sarcolemmal membranes of patients with end-stage heart failure. 2. Among 22 consecutive patients with chronic heart failure who underwent cardiac transplantation, those treated with a beta-blocker (n=8) had a 65% lower NDPK content and activity in the cardiac sarcolemma, compared to patients with similar base line characteristics who had no beta-blocker therapy (n=14). 3. The lower NDPK was associated with a reduced NDPK-dependent, Gi-mediated inhibition of adenylyl cyclase activity, as assessed by in vitro measurement of adenylyl cyclase activity in the presence of GDP or its kinase-resistant analog guanosine 5'-O-(2-thio)diphosphate (GDPbetaS). 4. We further tested whether treatment with a beta-adrenergic agonist would induce an increase in sarcolemmal NDPK. Rats treated with isoproterenol developed myocardial hypertrophy, and NDPK in the sarcolemma rose by 60% during 14 days of treatment. The beta-blocker propranolol prevented both effects. When hypertrophy was induced with thyroid hormone, NDPK did not increase. 5. In conclusion, chronic activation of beta-adrenergic receptors increases the binding of NDPK to cardiac sarcolemma, where it may activate heterotrimeric G proteins.
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PMID:Plasma membrane-associated nucleoside diphosphate kinase (nm23) in the heart is regulated by beta-adrenergic signaling. 1455 58

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid and thyroid hormone receptors. The PPAR subfamily comprises of three members, PPAR-alpha, PPAR-beta and PPAR-gamma. There is good evidence that ligands of PPAR-gamma, including certain thiazolinediones, reduce myocardial tissue injury and infarct size. The use of PPAR-gamma agonists in the treatment of heart failure is, however, controversial.
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PMID:Ligands of the peroxisome proliferator-activated receptor-gamma and heart failure. 1530 52

Digoxin, which is one of the most commonly prescribed drugs for the treatment of heart failure, is mainly eliminated from the circulation by the kidney. P-glycoprotein is well characterized as a digoxin pump at the apical membrane of the nephron. However, little is known about the transport mechanism at the basolateral membrane. We have isolated an organic anion transporter (OATP4C1) from human kidney. Human OATP4C1 is the first member of the organic anion transporting polypeptide (OATP) family expressed in human kidney. The isolated cDNA encodes a polypeptide of 724 aa with 12 transmembrane domains. The genomic organization consists of 13 exons located on chromosome 5q21. Its rat counterpart, Oatp4c1, is also isolated from rat kidney. Human OATP4C1 transports cardiac glycosides (digoxin, K(m) = 7.8 microM and ouabain, K(m) = 0.38 microM), thyroid hormone (triiodothyronine, K(m) = 5.9 microM and thyroxine), cAMP, and methotrexate in a sodium-independent manner. Rat Oatp4c1 also transports digoxin (K(m) = 8.0 microM) and triiodothyronine (K(m) = 1.9 microM). Immunohistochemical analysis reveals that rat Oatp4c1 protein is localized at the basolateral membrane of the proximal tubule cell in the kidney. These data suggest that human OATP4C1/rat Oatp4c1 might be a first step of the transport pathway of digoxin and various compounds into urine in the kidney.
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PMID:Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. 1499 4

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid and thyroid hormone receptors. The PPAR subfamily comprises of three members, PPAR-alpha, PPAR-beta and PPAR-gamma. There is good evidence that ligands of PPAR-gamma, including certain thiazolinediones, reduce myocardial tissue injury and infarct size. The use of PPAR-gamma agonists in the treatment of heart failure is, however, controversial.
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PMID:Ligands of the peroxisome proliferator-activated receptor-gamma and heart failure. 1466 33

Most patients with dilated cardiomyopathy have a poor prognosis due to progressive and irreversible myocardial dysfunction. Rarely, is a metabolic etiology responsive to specific therapy identified. Although many studies have confirmed that thyroid hormone deficiency is associated with a reversible decrease in myocardial contractility, it has remained controversial whether hypothyroidism alone can cause a dilated cardiomyopathy and clinical heart failure. In this study, we report the case of a patient with severe hypothyroidism and a dilated cardiomyopathy complicated by heart failure, which has receded after recovery to euthyroidism with L-thyroxin therapy. This case suggests that hypothyroidism should be evoked systematically when a dilated cardiomyopathy is diagnosed.
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PMID:[Hypothyroid dilated cardiomyopathy]. 1536 18

This study was designed to determine if the thyroid hormone analog 3,5 diiodothyropropionic acid (DITPA), now in clinical trials for heart failure, alters endothelial function after myocardial infarction (MI). Three weeks after MI, adult Sprague-Dawley rats were randomly assigned to DITPA (375 microg/100 g subcutaneous) or no treatment of 3 weeks. In MI rats, left ventricular (LV) end-diastolic pressure and LV dP/dt decreased (P < 0.05). DITPA did not change MAP (87 +/- 10 versus 90 +/- 7 mm Hg) or LV end-diastolic pressure (23 +/- 3 versus 19 +/- 9 mm Hg) but did lower (P < 0.05) LV dP/dt (4,633 +/- 797 versus 3,650 +/- 1,236 mm Hg/s). In aortic segments from MI rats, DITPA enhanced the acetylcholine dependent vasorelaxation (59 +/- 11% at 10(-4) M, P < 0.05) and isoproterenol induced vasorelaxation (57 +/- 13% at 10(-4) M, P < 0.05). The increases in vasorelaxation were blocked with l-NAME and restored with L-arginine. Treatment with DITPA increased (P < 0.05) eNOS protein content in aortic tissue from sham rats (3.8 +/- 2.8 to 44.5 +/- 7.1 integrated intensity units (II)/microg) and in MI rats (5.3 +/- 3.4 to 28.3 +/- 8.9 II/microg). In endothelial cells, 24 hours' treatment with DITPA (10 microM) increased (P < 0.01) eNOS protein expression from 22.1 +/- 4.8 to 52.7 +/- 16.8 II/microg protein and DITPA (20 microM) increased eNOS to 49.1+/- 15.2 II/microg protein. The thyroid analog DITPA enhances endothelial nitric oxide and beta-adrenergic-mediated vasorelaxation by increasing nitric oxide in the vasculature.
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PMID:Thyroid hormone analog, DITPA, improves endothelial nitric oxide and beta-adrenergic mediated vasorelaxation after myocardial infarction. 1545 53


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