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

We investigated the time course of electrocardiographic (ECG) changes in the Mongolian gerbil model of iron overload and the effects of the iron chelator deferoxamine (DFO) on these changes. Iron overload was produced with weekly subcutaneous injections of low doses (200 mg/kg/wk) or high doses (800 mg/kg/wk) of iron-dextran. DFO was administered subcutaneously at a dose of 200 mg/kg/day to high-dose animals. Our results show that (1) survival of iron-overloaded gerbils is dose-dependent, with median survival times of 68 and 14 weeks for low- and high-dose animals, respectively; (2) both low and high doses produce prolongation of the PR interval and bradycardia in early stages and prolongation of the QT interval, premature ventricular contractions, variable degrees of atrioventricular block, changes in the ST segment, and T-wave inversion at later stages coinciding with the development of heart failure; (3) DFO prevented death during 20 weeks of high-dose iron-dextran; (4) DFO prevented ECG changes, although delayed prolongation of PR intervals and QRS complexes occurred; and (5) despite marked prolongation of survival and prevention of ECG changes, DFO had modest effects on total cardiac iron content. We speculate that DFO chelates a small iron pool located within the cytoplasm of iron-overloaded cardiomyocytes.
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PMID:Deferoxamine promotes survival and prevents electrocardiographic abnormalities in the gerbil model of iron-overload cardiomyopathy. 1496 69

Individuals with primary or secondary abnormalities of iron metabolism, such as hereditary hemochromatosis and transfusional iron loading, may develop potentially lethal systemic iron overload. Over time, this excess iron is progressively deposited in the liver, heart, pancreas, and other organs, resulting in cirrhosis, heart disease, diabetes and other disorders. Unless treated, death usually results from cardiac failure. The amount of iron in the liver is the best indicator of the amount of iron in the whole body. At present, the only sure way to measure the amount of iron in the liver is to remove a sample of the liver by biopsy. Iron stored in the liver can be magnetized to a small degree when placed in a magnetic field. The amount of magnetization is measured by our instrument, called a superconducting quantum interference device (SQUID) susceptometer. In patients with iron overload, our previous studies have shown that magnetic measurements of liver iron in patients with iron overload are quantitatively equivalent to biochemical determinations on tissue obtained by biopsy. The safety, ease, rapidity, and comfort of magnetic measurements make frequent, serial studies technically feasible and practically acceptable to patients.
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PMID:SQUID biosusceptometry in the measurement of hepatic iron. 1276 53

Cardiac disease with arrhythmia or heart failure is the leading cause of death in patients with thalassemia major and a major complication of other forms of iron overload. Current antiarrhythmic treatment does not appear to alter the clinical course. Using a gerbil model of iron-overload cardiomyopathy, we previously observed a reduction in the fast inward sodium current in isolated cardiomyocytes. Electrocardiograms (ECGs) in the same gerbil model indicate PR-interval prolongation, QRS-interval widening, and arrhythmias. We hypothesize that such changes in the ECG in this model are the result of abnormal action-potential conduction at the level of the whole heart. To test this hypothesis, we took ECGs and recorded action potentials using high-resolution optical mapping from the anterior surface of 9 iron-overloaded and 9 age-matched control ventricular-paced, Langendorff-perfused gerbil hearts. The iron-overloaded gerbils received weekly iron-dextran injections of 800 mg/kg for 14 to 18 weeks. ECGs showed QRS- and PR-interval prolongation in iron-treated gerbils compared with that in controls. In addition, atrioventricular block was observed in 2 of 6 iron-treated gerbils but not in controls. Conduction velocity was significantly slower in iron-treated gerbils than in controls. At normal pacing rates, abnormal activation patterns caused by stable regions of conduction block were observed in iron-overloaded gerbils (33%) but not in controls. Such abnormal impulse conduction may be a mechanism of increased arrhythmia vulnerability in iron-overload cardiomyopathy.
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PMID:Optical mapping reveals conduction slowing and impulse block in iron-overload cardiomyopathy. 1296 Sep 54

EPIDEMIOLOGY ADN PHYSIOPATHOLOGY: Hereditary haemochromatosis is the most common genetic disease in France. Its frequency is on average 1 out of 300 French individuals. It is due to excessive dietary iron absorption, leading to accumulation of iron in the body. Mutations of the HFE1 gene are responsible for the majority of the case of haemochromatosis. FROM A CLINICAL POINT OF VIEW: The first clinical manifestations (weakness, sexual dysfunction, arthralgia, cardiac symptoms, dyspnoea on effort) can occur after the age of 30 years in men and 35 years in women (protected for longer by menstruation, pregnancy and delivery). In the absence of diagnosis, severe complications can develop during the 5th decade: nervous breakdown, arthropathy, heart failure, diabetes mellitus, cirrhosis with risk of progression towards carcinoma, responsible for handicaps and premature death. DIAGNOSTIC ELEMENTS: The diagnosis is evoked in the case of an increase in transferrine saturation (>45%), associated or not with excessive ferritin plasma levels. It is confirmed by the genetic test, showing homozygotes for the C282Y mutation or compound heterozygotes for the C282Y and H63D mutations on the HFE1 gene. RMI quantifies hepatic iron loading and generally avoids the need for a liver biopsy. The differential diagnosis must exclude secondary iron overload due to chronic transfusions in congenital or acquired blood diseases, a polymetabolic syndrome, chronic viral or alcoholic hepatic diseases and porphyria cutanea tarda. EFFICIENT TREATMENT: Today, haemochromatosis is still treated by phlebotomy. This consists in withdrawing 400 to 500ml of blood every week at the initial depletion stage and subsequently a maintenance therapy in order to maintain ferritin levels below 50 ng/ml. Paradoxically and through ignorance, hereditary haemochromatosis remains a serious disease, although its diagnosis is easy and the treatment simple and effective.
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PMID:[Hereditary haemochromatosis]. 1579 37

Chronic iron overload is a major cause of cardiac failure throughout the world, but its pathogenesis remains to be clarified. It is conjectured that the toxicity of iron is due to its ability to catalyze the formation of oxygen free radicals (OFR), which can damage cellular membranes, proteins, and DNA. The authors report on the cardioprotective effects of the glutathione peroxidase (GPx) mimic ebselen on iron concentrations in the heart and GPx activity, and on the production of the cytotoxic aldehydes hexanal, 4-hydroxyl-2-nonenal (HNE), and malondialdehyde (MDA). Fifteen B6D2F1 mice were randomized to 1 of 3 treatment groups for a total of 20 treatments: 1) control (0.1 mL normal saline i.p. per mouse, per day); 2) iron-only (10 mg iron dextran i.p. per mouse, per day); 3) iron plus ebselen (25 mg/kg p.o. per mouse, per day). In comparison to iron-only treated mice, the authors' findings show that supplementation with ebselen can decrease both cytotoxic aldehyde and iron concentrations in heart tissue. Additionally, mice supplemented with ebselen had an increase in GPx activity level in comparison to iron-only treated mice. To the authors' knowledge, this is the first study to examine the cardioprotective effects of ebselen against OFR damage in a model of chronic iron overload. These findings suggest that ebselen may have significance in the management of disorders of iron overload.
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PMID:Ebselen decreases oxygen free radical production and iron concentrations in the hearts of chronically iron-overloaded mice. 1518 6

Iron's chemical structure and its ability to initiate one-electron reactions are properties that cause it to play a major role in the production and metabolism of oxygen free radicals in biological systems. Oxygen free radicals are conjectured to cause cardiac failure in individuals afflicted with disorders of iron overload. We report on the use of both acyloins and aldehydes as markers of oxidative stress in a murine model of chronic iron-overload cardiomyopathy. Twenty mice were randomized to four treatment groups: (1) control (0.2 mL normal saline ip/mouse/d); (2) 100 mg iron (0.05 mL iron dextran/mouse/d); (3) 200 mg iron (0.1 mL iron dexxtran/mouse/d); (4) 400 mg iron (0.2 mL iron dextran/mouse/d). Significant dose-dependent increases in both total heart aldehyde and total heart acyloin concentrations were found. Furthermore, a significant positive correlation existed between the dose of iron administered and each quantified aldehyde and acyloin found in the heart.
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PMID:Dose-dependent effects of chronic iron burden on heart aldehyde and acyloin production in mice. 1523 57

Heart failure from iron overload causes 71% of deaths in thalassaemia major, yet reversal of siderotic cardiomyopathy has been reported. In order to determine the changes in myocardial iron during treatment, we prospectively followed thalassaemia patients commencing intravenous desferrioxamine for iron-induced cardiomyopathy during a 12-month period. Cardiovascular magnetic resonance assessments were performed at baseline, 3, 6 and 12 months of treatment, and included left ventricular (LV) function and myocardial and liver T2*, which is inversely related to iron concentration. One patient died. The six survivors showed progressive improvements in myocardial T2* (5.1 +/- 1.9 to 8.1 +/- 2.8 ms, P = 0.003), liver iron (9.6 +/- 4.3 to 2.1 +/- 1.5 mg/g, P = 0.001), LV ejection fraction (52 +/- 7.1% to 63 +/- 6.4%, P = 0.03), LV volumes (end diastolic volume index 115 +/- 17 to 96 +/- 3 ml, P = 0.03; end systolic volume index 55 +/- 16 to 36 +/- 6 ml, P = 0.01) and LV mass index (106 +/- 14 to 95 +/- 13, P = 0.01). Iron cleared more slowly from myocardium than liver (5.0 +/- 3.3% vs. 39 +/- 23% per month, P = 0.02). These prospective data confirm that siderotic heart failure is often reversible with intravenous iron chelation with desferrioxamine. Myocardial T2* improves in concert with LV volumes and function during recovery, but iron clearance from the heart is considerably slower than from the liver.
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PMID:Myocardial iron clearance during reversal of siderotic cardiomyopathy with intravenous desferrioxamine: a prospective study using T2* cardiovascular magnetic resonance. 1549 Dec 98

In addition to the severe beta thalassemias, hematologists have begun to recognize the more severe forms of alpha thalassemia, namely hemoglobin (Hb) H disease and Hb H/Hb Constant Spring, as well as the beta compound heterozygote, beta thalassemia/HbE. Clinically, variably severe anemia becomes apparent in the first year accompanied by occasionally massive expansion of erythropoiesis. The most anemic patients require regular red blood cell transfusions to avoid death from cardiac failure. However, the inevitable iron accumulation leads to dysfunction, primarily involving the heart, liver, and endocrine system; thus, regularly transfused patients require iron chelation. A major discovery was that allogeneic bone marrow (stem cell) transplantation in severely affected subjects with both alpha and beta thalassemia could result in cure. Current work deals with specific complications, such as iron overload and endocrine, cardiopulmonary, thrombophilic, and osteopenic problems. The thalassemias are likely to benefit in the future from specific gene therapy. There are also important advances in genetic counseling based on results of early fetal diagnosis.
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PMID:New strategies in the treatment of the thalassemias. 1566 May 7

The anaemia of chronic kidney disease (CKD) is efficiently corrected with a combination of recombinant erythropoietin (rhEPO) and intravenous iron supplementation. Recently, patients with severe cardiac failure and anaemia have also been shown to benefit from this treatment. However, iron excess may lead to the production of free radicals and has been incriminated in the pathogenesis of atherosclerosis and increased risk of infection, the two major causes of death in end-stage renal disease. The exact risk of excess iron supplementation has not been defined and, in the absence of sensitive and specific indicators of iron overload, the risk remains difficult to quantify. There is increasing epidemiological evidence incriminating iron overload as a risk factor in CKD, but direct evidence is still hard to obtain. The precise role of iron is complicated further by the complex inter-relationships between iron metabolism and the inflammatory process characteristic of CKD. The recent discovery of the antimicrobial peptide, hepcidin, may shed light on these inter-relationships. New methods for quantifying non-transferrin-bound (or labile plasma) iron may help in the future to identify patients at risk for toxicity from excess iron supplementation.
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PMID:Intravenous iron supplementation in the anaemia of renal and cardiac failure--a double-edged sword? 1602 27

Although the indications for transfusions in sickle cell syndromes are well listed, and chronic transfusion has become practicable since the recent advances in chelation therapy have essentially eliminated the risk of secondary iron overload, multi-transfused, non-compliant to long-term chelation therapy patients confront the complication of iron overload and secondary hemosiderosis. In thalassemia major patients, combined therapy with desferrioxamine and deferiprone has maximized tissue iron removal and may reduce the overall occurrence of hemosiderotic heart failure. Despite this, safety and contradictions of chelating agents are still controversial. The aim of this report is to present the results of this combination in a long-term transfused sickle beta-thalassemic patient suffering from severe heart failure and liver dysfunction.
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PMID:Transfusional hemosiderosis and combined chelation therapy in sickle thalassemia. 1614 44


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