UMLS:C0018801 - FACTA Search

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

GH exerts direct effects on myocardial growth and function. Evidence from laboratory models shows that GH (or IGF-I) induces mRNA expression for specific contractile proteins and myocyte hypertrophy. Furthermore, GH increases the force of contraction and determines myosin phenoconversion toward the low ATPase activity V3 isoform. These data provide plausible explanations for the cardiac abnormalities observed in clinical settings of excessive or defective GH production. In acromegaly, the functional consequences of GH excess initially prevail (hyperkinetic syndrome), followed by alterations of cardiac function when myocardial hypertrophy develops. This involves both ventricles and is purposeless because it occurs without increased wall stress. Hypertrophy also entails proliferation of the myocardial fibrous tissue that leads to interstitial remodeling. The functional consequence is an impaired ventricular relaxation that causes a diastolic dysfunction, followed by impairment of systolic function. In untreated disease, cardiac performance slowly but inexorably deteriorates and heart failure eventually develops. Several lines of evidence support the specificity of heart disease in acromegaly. Particularly demonstrative are the recent studies in which GH production was suppressed by octreotide, with a consequent significant regression of hypertrophy and improvement of cardiac dysfunction. It is not yet established whether full recovery of normal cardiac morphology and function is possible after correction of GH excess. The point is not a minor one since the possibility to revert, albeit partially, myocardial fibrosis is of great relevance to the control of cardiac hypertrophy in general. GHD leads to a reduced mass of both ventricles and to impaired cardiac performance with low heart rate (hypokinetic syndrome). These alterations are particularly evident during physical exercise and might provide an important contribution to the reduced exercise capacity of GHD patients, in addition to the reduced muscle mass and strength. The data also support a role of GH in the maintenance of a normal cardiac structure and performance. The hypokinetic syndrome is well documented in young patients in whom GHD began very early in their childhood. In contrast, the data in adult-onset GHD are less consistent. This suggests that the consequences of GHD are more relevant if the disorder starts during early heart development. As observed with other abnormalities associated with GHD, cardiac dysfunction is also susceptible to marked improvement by hrGH. This observation lends further support to the proposal to treat these patients with replacement therapy.
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PMID:Growth hormone and the heart. 784 68

At present, there is growing evidence implicating GH and/or IGF-I in the intricate cascade of events connected with the regulation of heart development and hypertrophy. Moreover, GH excess and/or deficiency have been shown to include in their advanced clinical manifestations almost always an impaired cardiac function, which may reduce life expectancy. This finding is related both to a primitive impairment of heart structure and function and to metabolic changes such as hyperlipidemia, increase of body fat and premature atherosclerosis. Patients with childhood or adulthood-onset GH deficiency have a reduced left ventricular mass and ejection fraction and the indexes of left ventricular systolic function remain markedly depressed during exercise. Conversely, in acromegaly the cardiac enlargement, which is disproportionate to the increase in size of other internal body organs, has been a rather uniform finding. The severity of the acromegalic cardiomyopathy was reported to be correlated better with the disease duration than with circulating GH and/or IGF-I levels. Myocardial hypertrophy with interstitial fibrosis, lymphomononuclear infiltration and areas of monocyte necrosis often results in concentric hypertrophy of both ventricles. The treatment of GH deficiency and excess improved cardiac function. Interestingly, based on the evidence that GH increases cardiac mass, recombinant GH was administered to patients with idiopathic dilated cardiomyopathy. It increased the myocardial mass and reduced the size of the left ventricular chamber, resulting in improvement of hemodynamics, myocardial energy metabolism and clinical status. These promising results open new perspectives for the use of GH in heart failure.
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PMID:Is growth hormone bad for your heart? Cardiovascular impact of GH deficiency and of acromegaly. 938 93

Post-traumatic stress-induced disorders are still the focus of interest and most recently discussions are under way whether stress-induced cortisol excess leads to atrophy of the brain. In investigation on carcinogenesis the first reports were published on the use of antisense-oligonucleotides during inhibition of the development of tumours by a humoral mechanism and on the gene-based neuroendocrine differentiation of the lungs, perhaps associated with the basis for the development of small cell carcinoma. The oncogenic action of superoxides has also humoral mediators. Interest in nitrogen oxide is focused on two areas: inflammations and hypertension. Intraluminal NO concentrations increase in asthma 2-10x, in cystitis 30-100x, in Crohn's disease 20-200x. Humoral mechanisms in asthma offer new drugs--inhibitors of the development or action of leucotrienes. The basal NO production is reduced in "essential" hypertension but it is not known whether it is the cause or consequence. IGF-I increases the formation of NO in the vascular wall and thus perhaps reduces vascular contractility. As far as IGF is concerned, it is obvious that if recombinant preparations will be available, they will be tested in amyotrophic lateral sclerosis, myotonic dystrophy, multiple sclerosis, catabolic conditions, osteoporosis, in renal failure and to promote wound healing. STH may also prove useful in cardiac failure, in particular in cardiac cachexia. That TRH has receptors in the gut is not surprising, it acts, however, even there via TSH. Thrombopoietin is being tested in clinical trials. Neocytolysis is a new phenomenon: when erythropoietin secretion declines new erythrocytes disappear and only old ones remain in the blood stream. Alpha-adducin is a renal tubular protein, regulating the sodium balance.
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PMID:[Endocrinology 1996-1997]. 965 Mar 40

Although cardiac effects of growth hormone (GH) and insulin-like growth factor (IGF)-I have been reported in experimental models of heart failure and in human dilated cardiomyopathy, the IGF system has not been comprehensively assessed in the failing heart. We therefore localized the IGF system in the left ventricle during congestive heart failure after myocardial infarction (MI) in the rat. The left anterior descending coronary artery was ligated in adult female Sprague-Dawley rats and hearts were examined after 6 months when congestive heart failure had developed. In situ hybridization histochemistry was used to localize mRNA for the components of the IGF system in the left ventricle of sham and congestive heart failure animals. We were able to detect changes in the spatial distribution of mRNA for IGF-I and IGF binding proteins 3, 4, 5, and 6 in the left ventricle during congestive heart failure after MI. IGF-I and the binding proteins were predominantly increased in the infarct/peri-infarct area of the left ventricle. Other components of the IGF system were indistinguishable from the low to undetectable levels in sham-operated rats. These results demonstrate that the IGF system is altered in the failing heart and suggest that the IGF system plays an important role in the response of the heart to MI and consequent failure.
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PMID:Localization of the insulin-like growth factor system in a rat model of heart failure induced by myocardial infarction. 1021 57

Two major cardiovascular effects of growth hormone (GH) are peripheral vasodilation and increased myocyte growth. Many of the effects of GH on the vascular system are mediated by insulin-like growth factor (IGF)-I. There is abundant evidence that IGF-I stimulates endothelial nitric oxide (NO) synthesis and thereby induces endothelium-dependent vasodilation in experimental models as well as in humans. NO is synthesized by a family of enzymes named NO synthases (NOS), of which three major isoforms have been isolated, cloned and characterized. In endothelial cells, NOS III is a constitutively expressed isoform of NOS which releases small amounts of NO in a calcium-dependent manner. Endothelium-derived NO is an important vasodilator, inhibitor of platelet adhesion and aggregation, inhibitor of monocyte adhesion and inhibitor of vascular smooth muscle cell growth. These pleiotropic cardiovascular actions of NO have been summarized in the characterization of NO as an endogenous antiatherosclerotic molecule. NO-mediated vasodilation is impaired in patients with acquired GH deficiency. Reduced GH-stimulated NO secretion may have important implications in the pathogenesis of heart failure associated with GH deficiency, as it contributes to peripheral vasoconstriction and, thereby, increases afterload. Baseline NO elaboration in patients with adult-onset GH deficiency is reduced compared with that in healthy controls. In GH-deficient patients, chronic substitution of recombinant human GH (rhGH) results in increased rates of synthesis of NO and decreased peripheral arterial resistance. Recent evidence also suggests that GH secretion is reduced in severe heart failure. In addition, GH resistance has been reported in patients with cardiomyopathy, as suggested by an elevated GH/IGF-I ratio. This may contribute to the progression of cardiac failure via a reduction in NO-mediated vasodilation. Clinical studies suggest that NO-mediated vasodilation is impaired in patients with heart failure. Treatment with rhGH may be beneficial in chronic heart failure via a dual action: improved myocardial performance, and peripheral vasodilation mediated via IGF-I/NO/cyclic guanosine monophosphate. This hypothesis deserves further investigation in clinical trials.
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PMID:Nitric oxide and the mediation of the hemodynamic effects of growth hormone in humans. 1044 75

Impaired cardiovascular function, which may reduce life expectancy, has recently been demonstrated both in GH deficiency and excess. Moreover, experimental and clinical studies support the evidence implicating GH and/or IGF-I in the regulation of heart development. The existence of a specific acromegalic cardiomyophathy characterized by myocardial hypertrophy with interstitial fibrosis, lympho-mononuclear infiltration and areas of monocyte necrosis which often result in biventricular concentric hypertrophy has been recenty demonstrated. By contrast, patients with childhood or adulthood-onset GH deficiency (GHD) present with abnormalities of structure and function of the left ventricle. In these patients, a significant increase in the vascular intima-media thickness and an increased number of atheromatous plaques have also been reported. The abnormalities of cardiovascular system could be partially reverted by suppressing GH and IGF-I levels in acromegaly or after GH remplacement therapy in GHD patients. The evidence that GH is able to increase cardiac mass suggested its use in the -treatment of chronic heart failure of diverse etiologies. GH administration was -demonstrated to induce an improvement in hemodynamics and clinical status in some patients. Although these data should be confirmed in double-blind placebo controlled studies in larger series, the promising results open new perspectives for GH treatment in humans.
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PMID:Growth hormone and cardiac function. 1079 May 87

These studies suggest that IGF-I and GH have generally favourable effects on the failing heart. They further demonstrate the ability of the severely depressed and failing heart to respond to the trophic and inotropic effects of GH. There is, however, a need for a better understanding of the mechanism of the contractility effect, the character of the hypertrophy observed (whether it is a more favourable type than that secondary to mechanical overload) and the vascular actions, both trophic and vasodilatory. In addition, the degree to which high-dose ACE inhibition or angiotensin II receptor blockade may inhibit some of these effects requires further study. Finally, it is clear that additional experimental studies and clinical trials are needed to investigate the long-term effects of GH on morbidity and mortality in heart failure, as well as the possible side-effects and other actions, such as the potential of GH to enhance skeletal muscle size and strength.
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PMID:Effects of growth hormone and insulin-like growth factor I in experimental heart failure. 1099 Jan 54

Impaired cardiovascular function has recently been demonstrated to potentially reduce life expectancy both in GH deficiency and excess. Experimental and clinical studies have supported the evidence that GH and IGF-I are implicated in cardiac development. In most patients with acromegaly a specific cardiomyopathy, characterized by myocardial hypertrophy with interstitial fibrosis, lympho-mononuclear infiltration and areas of monocyte necrosis, results in biventricular concentric hypertrophy. In contrast, patients with childhood or adulthood-onset GH deficiency (GHD) may suffer both from structural cardiac abnormalities, such as narrowing of cardiac walls, and functional impairment, that combine to reduce diastolic filling and impair left ventricular response to peak exercise. In addition, GHD patients may have an increase in vascular intima-media thickness and a higher occurrence of atheromatous plaques, that can further aggravate the haemodynamic conditions and contribute to increased cardiovascular and cerebrovascular risk. However, several lines of evidence have suggested that the cardiovascular abnormalities can be partially reversed by suppressing GH and IGF-I levels in acromegaly or after GH replacement therapy in GHD patients. Recently, much attention has been focussed on the ability of GH to increase cardiac mass suggesting its possible use in the treatment of chronic nonendocrine heart failure. In fact, GH administration can induce an improvement in haemodynamic and clinical status in some patients. Although these data need to be confirmed in more extensive studies, such promising results seem to open new perspectives for GH treatment in humans.
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PMID:Growth hormone and the heart. 1120 26

Beneficial effects of recombinant human GH on cardiac function have been reported in humans with GH deficiency and in patients with idiopathic dilated cardiomyopathy. No randomized controlled trial has been performed on the effects of recombinant human GH on cardiac function in patients with ischemic cardiac failure. We therefore randomly assigned 22 patients with ischemic cardiac failure (left ventricular ejection fraction, <40%; 19 men and 3 women; mean age, 64 yr) to receive 6 months of unblinded therapy with recombinant human GH (2.0 IU/d) or no treatment. Primary end points were left ventricular ejection fraction and left ventricular mass. Left ventricular end-diastolic volume, left ventricular end-systolic volume, and myocardial perfusion, both at rest and during exercise, were assessed as well. Cardiac imaging techniques were electrocardiographically gated single photon emission computer tomography and magnetic resonance imaging. In addition, biochemical and biometric measurements were performed. Nineteen patients completed the study (10 controls and 9 GH-treated subjects). IGF-I and IGF-binding protein-3 increased significantly after recombinant human GH treatment (+24% and +58%, respectively) compared with control values (-14% and +5%; P < 0.05). Left ventricular ejection fraction, left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular mass, and myocardial perfusion were not influenced by recombinant human GH therapy. We conclude that 6 months of recombinant human GH treatment in patients with ischemic cardiac failure had no beneficial effect on left ventricular function and mass.
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PMID:Six months of recombinant human GH therapy in patients with ischemic cardiac failure does not influence left ventricular function and mass. 1160 May 17

Chronic obstructive pulmonary disease, COPD is a highly prevalent disorder of increasing medical and socio-economical importance. It is characterized by irreversible airflow obstruction. Besides airflow obstruction also other features are present. One of these is respiratory muscle weakness. Inspiratory muscle weakness is caused by hyperinflation and by generalized muscle weakness causing both respiratory and peripheral muscle dysfunction. The expiratory muscles partake in this generalized muscle weakness. Hyperinflation shortens the inspiratory muscles although in chronic hyperinflation sarcomere adaptation occurs. Generalized muscle weakness is caused by deconditioning, malnutrition, electrolyte disturbances, cardiac failure, systemic inflammation and treatment with corticosteroids causing steroid-induced myopathy. The latter disease was studied intensively both in patients and in animal models of disease. The major findings were that microscopically a myopathic pattern was present associated with generalized fiber atrophy. This is in contrast to classical belief that the atrophy would be confined to type IIx fibers. We noted severe down-regulation of the IGF-I mRNA expression, without important changes in the expression of the binding proteins. This may be responsible for the observed muscle atrophy and the myopathy. The latter is likely to be caused by a simultaneous upregulation of the ubiquitin protease pathway attacking structural proteins. Presently, we study the relationship between local and systemic cytokine expression and respiratory and peripheral muscle dysfunction in COPD patients. Respiratory and peripheral muscle dysfunction have significant consequences for COPD patients. Both respiratory and peripheral muscle dysfunction are associated with reduced exercise tolerance and reduced quality of life. Both are independent determinants of survival, in addition to the degree of airflow obstruction as measured by FEV1. Finally, also the utilization of health care resources appeared to be related to respiratory and peripheral muscle weakness. Treatment of respiratory and peripheral muscle weakness in COPD patients is possible. Respiratory and peripheral muscle training have been shown to produce beneficial effects. Nutritional intervention and anabolic steroids are only useful in combination with muscle training. Systemic administration of growth hormone and IGF-I only produces small effects. In animal models, local administration of IGF-I and transfer of the IGF-I gene transfer appear more promising for the future. Lung volume reduction surgery, LVRS, improves the force-generating capacity of the inspiratory muscles, presumably because of the geometrical alterations it causes in these muscles. It does not appear to improve intrinsic inspiratory muscle function.
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PMID:Respiratory muscles in COPD: regulation of trophical status. 1181 11

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