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

The presence of a diabetic cardiomyopathy, independent of hypertension and coronary artery disease, is still controversial. This systematic review seeks to evaluate the evidence for the existence of this condition, to clarify the possible mechanisms responsible, and to consider possible therapeutic implications. The existence of a diabetic cardiomyopathy is supported by epidemiological findings showing the association of diabetes with heart failure; clinical studies confirming the association of diabetes with left ventricular dysfunction independent of hypertension, coronary artery disease, and other heart disease; and experimental evidence of myocardial structural and functional changes. The most important mechanisms of diabetic cardiomyopathy are metabolic disturbances (depletion of glucose transporter 4, increased free fatty acids, carnitine deficiency, changes in calcium homeostasis), myocardial fibrosis (association with increases in angiotensin II, IGF-I, and inflammatory cytokines), small vessel disease (microangiopathy, impaired coronary flow reserve, and endothelial dysfunction), cardiac autonomic neuropathy (denervation and alterations in myocardial catecholamine levels), and insulin resistance (hyperinsulinemia and reduced insulin sensitivity). This review presents evidence that diabetes is associated with a cardiomyopathy, independent of comorbid conditions, and that metabolic disturbances, myocardial fibrosis, small vessel disease, cardiac autonomic neuropathy, and insulin resistance may all contribute to the development of diabetic heart disease.
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PMID:Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications. 1529 81

Cardiovascular disease is claimed to be one of the most severe complications of acromegaly, contributing significantly to mortality in this disease. In fact, an excess of growth hormone (GH) and insulin-like growth factor 1 (IGF-I) causes a specific derangement of cardiomyocytes, leading to abnormalities in cardiac muscle structure and function, inducing a specific cardiomyopathy. In the early phase of acromegaly the excess of GH and IGF-I induces a hyperkinetic syndrome, characterized by increased heart rate and increased systolic output. Concentric hypertrophy is the most common feature of cardiac involvement in acromegaly, found in more than two thirds of patients at diagnosis. This abnormality is commonly associated with diastolic dysfunction and eventually with impaired systolic function ending in heart failure, if the GH/IGF-I excess is left untreated. In addition, abnormalities of cardiac rhythm and of heart valves have also been described in acromegaly. The coexistence of other complications, such as arterial hypertension and diabetes mellitus, aggravates acromegalic cardiomyopathy. Successful control of acromegaly induces a decrease in left ventricular mass and an improvement in diastolic function, while the effects of GH/IGF-I suppression on systolic function are more variable. However, since cardiovascular alterations in young patients with short disease duration are milder than in those with longer disease duration, it is likely to be easier to reverse and/or arrest acromegalic cardiomyopathy in young patients with early-onset disease. In conclusion, careful assessments of cardiac function, morphology, and activity are required in patients with acromegaly. An early diagnosis and prompt effective treatment are important in order to reverse acromegalic cardiomyopathy.
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PMID:Cardiac abnormalities in acromegaly. Pathophysiology and implications for management. 1533 Jun 78

Several experimental and clinical studies have indicate that the heart is an end-organ of GH action. Patients with either childhood- or adulthood-onset GH deficiency (GHD) have abnormalities of cardiac structure and function, such as reduced cardiac mass, impaired diastolic filling and reduced left ventricular response at peak exercise. These cardiovascular abnormalities can be reversed, at least partially, after GH replacement therapy. On the other hand, the chronic overproduction of GH and IGF-I in acromegaly leads to the development of a specific cardiomyopathy. Concentric cardiac hypertrophy occurs in more than two-thirds of patients at diagnosis and is commonly associated with diastolic dysfunction. In later stages, impaired systolic function ending in heart failure can occur if GH/IGF-I excess is not controlled. Additionally, acromegalic cardiomyopathy is complicated by abnormalities of cardiac rhythm and cardiac valves. Successful control of acromegaly is accompanied by a decrease of the left ventricular mass and improvement of cardiac function. These beneficial effects appear earlier in young patients with short disease duration than in elderly patients. In conclusion, GH and IGF-I play a main role in the regulation of cardiac development and performance.
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PMID:The heart: an end-organ of GH action. 1533 52

Hearts from severely Cu-deficient rats show a variety of pathological defects, including hypertrophy and, in intact hearts, depression of contractile function. Paradoxically, isolated cardiomyocytes from these rats exhibit enhanced contractile properties. Because hypertrophy and enhanced contractility observed with other pathologies are associated with elevation of insulin-like growth factor-I (IGF)-I, this mechanism was examined for the case of dietary Cu deficiency. Male, weanling Sprague-Dawley rats were provided diets that were deficient (approximately 0.5 mg Cu/kg diet) or adequate (approximately 6 mg Cu/kg diet) in Cu for 5 wk. IGF-I was measured in serum and hearts by an ELISA method, cardiac IGF-I and IGF-II receptors and IGFBP-3 were measured by Western blotting analysis, and mRNAs for cardiac IGF-I and IGF-II were measured by RT-PCR. Contractility of isolated cardiomyocytes was assessed by a video-based edge-detection system. Cu deficiency depressed serum and heart IGF-I and heart IGFBP-3 protein levels and increased cardiac IGF-I receptor protein. Cardiac IGF-II protein and mRNA for cardiac IGF-I and IGF-II were unaffected by Cu deficiency. A Cu deficiency-induced increase in cardiomyocyte contractility, as indicated by increases in maximal velocities of shortening (-dL/dt) and relengthening (+dL/dt) and decrease in time to peak shortening (TPS), was confirmed. These changes were largely inhibited by use of H-1356, an IGF-I receptor blocker. We conclude that enhanced sensitivity to IGF-I, as indicated by an increase in IGF-I receptor protein, accounts for the increased contractility of Cu-deficient cardiomyocytes and may presage cardiac failure.
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PMID:Increased contractility of cardiomyocytes from copper-deficient rats is associated with upregulation of cardiac IGF-I receptor. 1573 78

An intriguing relationship between IGF-I action and cardiac function has been noted for some time, but exactly how IGF-I modulates myocardial function remained obscure. Recent research shed novel insight into potential mechanisms of IGF-I actions in cardiac muscle. New discoveries help elucidate the role of IGF-I signaling in protecting cardiac muscle against injuries, and support potential therapeutic roles for IGF-I in cardiomyopathy. Multiple actions of IGF-I has been described in cardiac muscle cells, including the well-documented anti-apoptosis effect and the newly emerged action on cardiac muscle regeneration. Furthermore, interplay between heat shock protein and IGF-I receptor signaling has been identified and this new paradigm might be involved in the development of diabetic cardiomyopathy. This article reviews recent research findings and outlines potential therapeutic implications of IGF-I in heart failure.
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PMID:IGF-I is a matter of heart. 1580 13

Several evidences point for beneficial effects of growth hormone (GH) in heart failure (HF). Taking into account that HF is related with changes in myocardial oxidative stress and in energy generation from metabolic pathways, it is important to clarify whether GH increase or decrease myocardial oxidative stress and what is its effect on energetic metabolism in HF condition. Thus, this study investigated the effects of two different doses of GH on energetic metabolism and oxidative stress in myocardium of rats with HF. Male Wistar rats (n=25) were submitted to aortic stenosis (AS). The HF was evidenced by tachypnea and echocardiographic criteria around 28 weeks of AS. The rats were then randomly divided into three groups: (HF) with HF, treated with saline (0.9% NaCl); (HF-GH1), treated with 1 mk/kg/day recombinant human growth hormone (rhGH), and (HF-GH2) treated with 2 mg/kg/day rhGH. GH was injected, subcutaneously, daily for 2 weeks. A control group (sham; n=12), with the same age of the others rats was evaluated to confirm data for AS. HF had lower IGF-I (insulin-like growth factor-I) than sham-operated rats, and both GH treatments normalized IGF-I level. HF-GH1 animals had lower lipid hydroperoxide (LH), LH/total antioxidant substances (TAS) and glutathione-reductase than HF. Glutathione peroxidase (GSH-Px), hydroxyacyl coenzyme-A dehydrogenase, lactate dehydrogenase(LDH) were higher in HF-GH1 than in HF. HF-GH2 compared with HF, had increased LH/TAS ratio, as well as decreased oxidized glutathione and LDH activity. Comparing the two GH doses, GSH-Px, superoxide dismutase and LDH were lower in HF-GH2 than in HF-GH1. In conclusion, GH effects were dose-dependent and both tested doses did not aggravate the heart dysfunction. The higher GH dose, 2 mg/kg exerted detrimental effects related to energy metabolism and oxidative stress. The lower dose, 1mg/kg GH exerted beneficial effects enhancing antioxidant defences, reducing oxidative stress and improving energy generation in myocardium of rats with heart failure.
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PMID:Growth hormone and heart failure: oxidative stress and energetic metabolism in rats. 1819

GH may exert direct growth-promoting and metabolic actions on target tissues, but most of its effects are mediated by circulating (endocrine) or local (auto-/paracrine) IGF-I. The GH/IGF-I system has an important role in cardiac development and in maintaining the structure and function of the heart. A subgroup of children with pronounced heart defects will eventually need transplants, owing to congestive heart failure. Since the symptoms are often severe and may progress while waiting for surgery, it is necessary to develop supportive medical treatment. GH has been proposed as a therapeutic agent in adults with heart failure, but to date studies are lacking on children and more information is necessary. We have examined the expression of IGF-I mRNA and GH-receptor (GH-R) mRNA in children undergoing surgery for congenital heart disease. Eighteen children scheduled for open-heart surgery were included in the study. Right auricular biopsies were taken at the time of venous catheterization preceding cardiac bypass. The specimens were analysed using realtime PCR. We were able to show expression of both IGF-I mRNA and GH-R mRNA in the pediatric heart. The relative expressions were intercorrelated (r=0.75, p<0.001). GH-R mRNA correlated positively to standardized weight (r=0.65, p=0.004), body mass index (BMI) (r=0.59, p=0.01), and standardized BMI (r=0.59, p=0.01). IGF-I mRNA only correlated to BMI (r=0.50, p=0.04). This is the first study displaying cardiac expression of IGF-I mRNA and GH-R mRNA in children with congenital heart disease, although further studies are needed to define a role for GH in the treatment of these patients.
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PMID:Relative cardiac expression of growth hormone receptor and insulin-like growth factor-I mRNA in congenital heart disease. 1840 Dec

COPD is a disease that is not confined to the airways and the lungs, but also produces systemic consequences. Muscle weakness is one of these. It is produced by a multitude of factors including deconditioning, systemic inflammation, oxidative stress, nutritional imbalance, reduced anabolic status, systemic corticosteroids, hypoxemia, hypercapnia, electrolyte disturbances, cardiac failure. The most important factors appear to be inactivity and systemic inflammation. Inactivity was shown to be present in patients with COPD from early in the course of the disease on. Systemic inflammation was shown to be predominantly present during COPD exacerbations. IL-6 has the propensity to reduce muscle function in experimental animals. At present there is no evidence of local production of cytokines in the muscle in patients with COPD. Muscle weakness is also important in the clinical course of the disease as it is associated with exercise intolerance, reduced quality of life, enhanced utilization of health care resources and reduced survival. Rehabilitation is the best treatment for muscle weakness and deconditioning in patients with COPD. Indeed, it is the intervention with the largest effect on health status and exercise capacity in these patients. Several factors that may enhance the effects of rehabilitation have been studied. These include: growth hormone/ IGF-I, anabolic steroids, clenbuterol, creatine, anti-cytokine treatment, erythropoietin, oxygen, non-invasive mechanical ventilation and electrical stimulation. Recently, the potential of protease-inhibitors in reversing deconditioning-induced muscle dysfunction was demonstrated. Adjuncts are potentially particularly useful in patients who do not respond to a rehabilitation programme. Analysis of large d-bases demonstrated that about one third of the patients does not respond to rehabilitation. A follow-up study suggests that decline in exercise capacity after a rehabilitation programme is particularly present in these patients and not in the patients with a clear initial response. A better understanding of the factors controlling the response to rehabilitation, may lead to significant advances in this field.
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PMID:Pulmonary rehabilitation 2007: from bench to practice and back. 1898 Jul 25

IGF-1 plays an important role in cardiovascular homeostasis, and plasma levels of IGF-1 correlate inversely with systolic function in heart failure. It is not known to what extent circulating IGF-1 secreted by the liver and local autocrine/paracrine IGF-1 expressed in the myocardium contribute to these beneficial effects on cardiac function and morphology. In the present study, we used a mouse model of liver-specific inducible deletion of the IGF-1 gene (LI-IGF-1 -/- mouse) in an attempt to evaluate the importance of circulating IGF-I on cardiac morphology and function under normal and pathological conditions, with an emphasis on its regulatory role in myocardial phosphocreatine metabolism. Echocardiography was performed in LI-IGF-1 -/- and control mice at rest and during dobutamine stress, both at baseline and post myocardial infarction (MI). High-energy phosphate metabolites were compared between LI-IGF-1 -/- and control mice at 4 weeks post MI. We found that LI-IGF-1 -/- mice had significantly greater left ventricular dimensions at baseline and showed a greater relative increase in cardiac dimensions, as well as deterioration of cardiac function, post MI. Myocardial creatine content was 17.9% lower in LI-IGF-1 -/- mice, whereas there was no detectable difference in high-energy nucleotides. These findings indicate an important role of circulating IGF-1 in preserving cardiac structure and function both in physiological settings and post MI.
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PMID:Importance of circulating IGF-1 for normal cardiac morphology, function and post infarction remodeling. 2310 37

The clinical conditions associated with GH excess and GH deficiency (GHD) are known to be associated with an increased risk for the cardiovascular morbidity and mortality, suggesting that either an excess or a deficiency in GH and/or IGF-I is deleterious for cardiovascular system. In patients with acromegaly, chronic GH and IGF-I excess commonly causes a specific cardiomyopathy characterized by a concentric cardiac hypertrophy associated with diastolic dysfunction and, in later stages, with systolic dysfunction ending in heart failure if GH/IGF-I excess is not controlled. Abnormalities of cardiac rhythm and anomalies of cardiac valves can also occur. Moreover, the increased prevalence of cardiovascular risk factors, such as hypertension, diabetes mellitus, and insulin resistance, as well as dyslipidemia, confer an increased risk for vascular atherosclerosis. Successful control of the disease is accompanied by a decrease of the cardiac mass and improvement of cardiac function and an improvement in cardiovascular risk factors. In patients with hypopituitarism, GHD has been considered the under- lying factor of the increased mortality when appropriate standard replacement of the pituitary hormones deficiencies is given. Either childhood-onset or adulthood-onset GHD are characterized by a cluster of abnormalities associated with an increased cardiovascular risk, including altered body composition, unfavorable lipid profile, insulin resistance, endothelial dysfunction and vascular atherosclerosis, a decrease in cardiac mass together with an impairment of systolic function mainly after exercise. Treatment with recombinant GH in patients with GHD is followed by an improvement of the cardiovascular risk factors and an increase in cardiac mass together with an improvement in cardiac performance. In conclusion, acromegaly and GHD are associated with an increased risk for cardiovascular morbidity and mortality, but the control of GH/IGF-I secretion reverses cardiovascular abnormalities and restores the normal life expectancy.
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PMID:The cardiovascular system in growth hormone excess and growth hormone deficiency. 2314 95


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