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

Growth hormone may affect cardiac function. In rats, chronic hypersecretion of growth hormone leads to increased maximum isometric contractile force of the left ventricular papillary muscle in vitro. In humans, administration of growth hormone can increase myocardial contractility. However, cardiac effects of growth hormone in heart failure or cardiac dysfunction have not been studied to date. The current study was to evaluate the cardiac effects of growth hormone in conscious rats with postinfarction left ventricular dysfunction and sham controls. Ligation of the left coronary artery or sham operation was performed, then 4 weeks after surgery, recombinant human growth hormone (2 mg/kg/day, SC) or vehicle was administered for 15 days. Catheters were implanted 13 days after treatment with growth hormone or vehicle. Hemodynamic parameters were measured in conscious rats 2 days after catheterization. In vehicle-treated rats, left ventricular systolic pressure, maximum dP/dt, and arterial pressure were significantly decreased and left ventricular end-diastolic pressure was significantly increased in the ligation group compared with sham controls. Growth hormone treatment increased left ventricular systolic pressure (p < 0.05) and dP/dt (p < 0.05) and reduced left ventricular end-diastolic pressure (p < 0.05), significantly in the ligated rats. In sham rats, growth hormone tended to decrease arterial pressure but did not alter ventricular contractility. Neither ligation nor growth hormone significantly altered heart rate and right atrial pressure. These results suggest that growth hormone treatment may improve cardiac function by increasing myocardial contractility in cardiac dysfunction or heart failure.
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PMID:Effects of growth hormone in rats with postinfarction left ventricular dysfunction. 778 32

To determine the effect of left ventricular and endocrine functions on linear growth in children with rheumatic heart disease (RHD) we studied 100 children and adolescents with RHD over a period of 1 year. The mean +/- SD for age of onset and duration of RHD were 7.3 +/- 3.8 years and 4.4 +/- 2.8, respectively. The cardiac lesions were mitral incompetence (n = 31), combined mitral and aortic incompetence (n = 64), and mitral stenosis (n = 5). Growth was assessed by determining both height standard deviation scores (HtSDS) and growth velocity standard deviation score (GVSDS) every 4 months, and sexual maturity was assessed according to Tanner's criteria. Two-hundred age-matched normal children served as controls for the growth data. Endocrine evaluation was performed in the 30 children with RHD who had age above 14 years (mean age 15.4 +/- 1.5 years), 20 age- and sex-matched normal children, and 20 age-matched children with constitutional delay of growth (normal variant short stature) (NVSS). Circulating concentrations of estradiol (E2) in girls, testosterone (T) in boys, and free T4 (FT4) were measured. Growth hormone (GH) response to clonidine provocation, LH and FSH response to LHRH stimulation, and in boys testosterone (T) response to HCG were evaluated. Echocardiographic evaluation of the left ventricular parameters was performed using a colour-coded echodoppler. The HtSDS and GVSDS of children with RHD were significantly lower than those for the normal control group. Delayed onset of puberty was evident in 16/30 of the children with RHD, and 6/ 30 more had sexual maturity score below 10th percentile for age and gender. In comparison with the age-matched normal group, those with RHD had significantly lower sexual maturity score (1.8 +/- 0.4 v. 3.25 +/- 0.8). All the children had normal GH response to clonidine provocation and normal FT4 concentrations. Basal and HCG stimulated T concentrations were significantly low in adolescents with RHD and E2 levels were non-significantly lower in girls with RHD compared to normal controls. LH response to LHRH was significantly decreased in RHD patients v. controls denoting delayed maturation of the hypothalamic-pituitary gonadal axis. HtSDS and GVSDS were correlated significantly with the left ventricular echocardiographic parameters, including left ventricular end diastolic diameter (LVEDD) (r = 0.57, and 0.617, respectively; P < 0.01), left ventricular end systolic diameter (LVESD) (r = 0.49, and 0.546, respectively; P < 0.01), left ventricular end diastolic volume (LVEDV) (r = 0.33 and 0.31, respectively; P < 0.05), left ventricular end systolic volume (LVESV) (r = 0.325 and 0.33, respectively; P < 0.05), peak velocity of circumferential fibres (Vcf) (r = 0.25 and 0.38, respectively; P < 0.05), and with pre-ejection period/ejection time (PEP/ET) (r = 0.14 and 0.47, respectively; P < 0.05). It appears that linear growth of children with RHD, without heart failure, depends on the left ventricular function. In addition, they have high incidence of delayed sexual development secondary to delayed maturation of their hypothalamic-pituitary gonadal axis.
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PMID:Growth parameters and endocrine function in relation to echocardiographic parameters in children and adolescents with compensated rheumatic heart disease. 907 21

Growth hormone (GH), probably acting indirectly through locally produced insulin-like growth factor I, stimulates myocardial hypertrophy and increases myocyte contractility. In experimental models insulin-like growth factor I appears to be a key regulator of ventricular hypertrophy. Many adults with growth hormone deficiency (GHD) have reduced left ventricular mass, a lower ejection fraction, and reduced exercise tolerance. Elevated serum lipid levels, increased visceral fat, and early atheroma formation may contribute to an increased mortality rate from cardiovascular disease in these persons, but GH replacement therapy appears to correct many of these abnormalities. GH excess (acromegaly) results in cardiac hypertrophy that can progress to cardiac failure. Treatment with octreotide at least partially reverses cardiac hypertrophy and dysfunction. GH treatment may induce beneficial cardiac hypertrophy in adults without GHD who have dilated cardiomyopathy. Significant cardiac dysfunction has not been reported in children with GHD who are treated with GH, nor have adverse cardiac effects been reported with GH in short children without GHD, including those with Turner syndrome. We now have extensive experience with the therapeutic use of GH in children with cardiac structural abnormalities (e.g., Turner and Noonan syndromes, congenital heart disease), and such use appears to be safe. Furthermore, cardiac complications of GH in children without cardiac disease are rare. Continued observation to ensure that GH therapy has no long-term effects on cardiac anatomy or function in children is necessary.
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PMID:Is growth hormone good for the heart? 925 33

The data from animal and human in-vivo studies suggest that cardiac function is dependent in part on the normal function of the GH/IGF-1 axis (growth hormone/insulin-like growth factor-1). The syndrome of heart failure appears to be associated with a perturbation of the GH/IGF-1 axis. So far encouraging results from phase II clinical trials evaluating the effects of long-term growth hormone treatment in patients with moderate to severe chronic congestive heart failure due to dilated cardiomyopathy have been published. In these studies growth hormone (i.e., DNA-derived recombinant human growth hormone) was not used alone but in addition to standard optimal therapy for chronic heart failure. The following rationale is the basis of this new approach for the treatment of chronic congestive heart failure due to dilated cardiomyopathy. According to Laplace's Law, cardiac wall stress(i.e., the force acting per unit of cross-sectional area of the ventricular wall) is directly related to intraventricular pressure and ventricular radius and inversely related to ventricular wall thickness. Cardiac (ventricular) wall stress if increased in dilated cardiomyopathy (mainly because of the dilatation of the ventricles and to a minor extent because of the relative reduction in ventricular thickness). Growth hormone seems to be capable of increasing ventricular wall thickness in dilated cardiomyopathy, thus, reducing cardiac wall stress which in turn leads to an improvement in systolic cardiac performance. Recombinant human growth hormone as a pharmacologic treatment is not only an expensive but also risky therapeutic modality (e.g., potential risk of inducing colonic carcinoma, de-novo leukemias, relapses of leukemias and central nervous system tumors). Given these prerequisites and a receptivity for cost effectiveness and risk-benefit analyses, it seems as if subcutaneous recombinant human growth hormone-as an additional therapeutic substance in conjunction with one of the widely accepted drugs for end-stage chronic congestive heart failure due to dilated cardiomyopathy-e.g., angiotensin converting-enzyme inhibitors, diuretics, nitrates, digoxin, and beta-adrenergic receptor blockers (Carvedilol) could either become a bridge to transplantation (i.e., supporting patients awaiting transplantation) or an alternative to the very expensive cardiac transplantation. There are three reasons for this hypothesis. First, the fact that end-state dilated cardiomyopathy along with ischemic heart disease are the main indications for heart transplantation in adults; second, the worldwide small supply of human donor organs for heart transplantation; and, third, the urgent need to find alternative cost-effective and risk-beneficial therapeutic modalities.
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PMID:[Therapy of terminal dilated cardiomyopathy with growth hormone]. 969 12

It has been reported that growth hormone may benefit selected patients with congestive heart failure. A 63-year-old man with refractory congestive heart failure waiting for heart transplantation, depending on intravenous drugs (dobutamine) and presenting with progressive worsening of the clinical status and cachexia, despite standard treatment, received growth hormone replacement (8 units per day) for optimization of congestive heart failure management. Increase in both serum growth hormone levels (from 0.3 to 0.8 microg/l) and serum IGF-1 levels (from 130 to 300ng/ml) was noted, in association with clinical status improvement, better optimization of heart failure treatment and discontinuation of dobutamine infusion. Left ventricular ejection fraction (by MUGA) increased from 13 % to 18 % and to 28 % later, in association with reduction of pulmonary pressures and increase in exercise capacity (rise in peak VO2 to 13.4 and to 16.2ml/kg/min later). The patient was "de-listed" for heart transplantation. Growth hormone may benefit selected patients with refractory heart failure.
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PMID:Growth hormone for optimization of refractory heart failure treatment. 1075 93

Cardiac hypertrophy is a major predictor of heart failure and of morbidity and mortality in developed countries. Many hormones and growth factors induce cardiac hypertrophy via activation of members of the phospholipase C (PLC) family. The expression pattern of the PLCbeta isozyme subfamily was investigated in neonatal rat cardiomyocytes after stimulation with different hypertrophic stimuli. Under control conditions and after stimulation with norepinephrine, cardiomyocytes expressed similar amounts of PLCbeta3 mRNA. In the presence of fetal calf serum (FCS), additional expression of PLCbeta1 was induced. Growth hormone (GH) and insulin-like growth factor-I (IGF-I) both induced a substantial increase in PLCbeta3 mRNA expression. The response to GH could not be abolished by the IGF-I receptor blocker IGF-I analogue indicating an IGF-I-independent action of GH. The upregulation of PLCbeta3 by IGF-I was abolished by preincubation of cardiomyocytes with the IGF-I receptor antagonist IGF-I analogue, the tyrosine kinase inhibitor genistein, the extracellular signal-related kinase (ERK) inhibitor PD 98059, the phosphatidylinositol-3- (PI-3) kinase inhibitor wortmannin and the p70 S6 kinase inhibitor rapamycin. Induction of the immediate early genes c-myc, c-fos, and c-jun by IGF-I was abolished by preincubation with antisense oligos against PLCbeta3. It is concluded that the expression of PLCbeta isozymes in cardiomyocytes is differentially regulated by different hypertrophic stimuli. The upregulation of PLCbeta3 by IGF-I is dependent on the activity of tyrosine kinase, ERK, PI3 kinase, and p70 S6 kinase and PLCbeta3 expression seems to be required for the induction of immediate early genes by IGF-I. The involvement of the PLCbeta subfamily in signal transduction of receptors other than G-protein-coupled receptors is suggested.
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PMID:Differential regulation of phospholipase C-beta isozymes in cardiomyocyte hypertrophy. 1094 30

Congestive heart failure is a multiple aetiology, high prevalence, poor prognosis cardiovascular disorder. Medical treatment of dilated cardiomyopathy is aimed at alleviating the symptoms of heart failure. Diuretics, ACE inhibitors and very recently, beta-blockers have been shown to have favourable effects on symptoms, exercise capacity and mortality. Growth hormone (GH) and insulin-like growth factor (IGF)-1 are involved in several physiological processes such as the control of muscle mass and function, body composition and regulation of nutrient metabolism. The roles of GH and IGF-1 as modulators of myocardial structure and function are well established. Receptors for both GH and IGF-1 are expressed by cardiac myocytes; therefore, GH may act directly on the heart or via the induction of local or systemic IGF-1, whereas IGF-1 may act by endocrine, paracrine or autocrine mechanisms. Patients with acromegaly have an increased propensity to develop ventricular hypertrophy and cardiovascular diseases and, in addition, an impaired cardiac efficiency is observed in patients with GH deficiency. Animal models of pressure and volume overload have demonstrated up-regulation of cardiac IGF-1 production and expression of GH and IGF-1 receptors, implying that the local regulation of these factors is influenced by haemodynamic changes. Moreover, experimental studies suggest that GH and IGF-1 have stimulatory effects on myocardial contractility, possibly mediated by changes in intracellular calcium handling. Heart failure is caused by ventricular dilatation with abnormal wall thickening, which leads to impaired cardiac performance; therefore, based on the evidence available for GH we would expect beneficial effects from the use of GH in these patients. Several papers highlight the positive influence of GH in the regulation of heart development and performance. In patients with GH deficiency, GH administration dramatically improves cardiac function. In small nonblind studies, both short and long term GH treatment have demonstrated beneficial effects in patients with heart failure secondary to ischaemic or idiophatic cardiomyopathy. Recently, two randomised, placebo-controlled studies, did not show significant GH-mediated improvement in cardiac performance in patients with dilated cardiomyopathy, despite significant increases in IGF-1. Acquired GH resistance, might be an important feature of severe heart failure and explain the different responses to GH therapy seen in different patients. Whether GH treatment will finally find a place, and with which modalities, in the treatment of heart failure remains to be established.
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PMID:Role of growth hormone in chronic heart failure. Therapeutic implications. 1108 97

Chronic heart failure is a multi-etiological cardiovascular disorder with high prevalence and poor prognosis. Medical treatment of dilated cardiomyopathy is aimed at alleviating heart failure symptoms. Diuretics, angiotensin-converting enzyme (ACE) inhibitors and very recently, beta-blockers have been shown to have favorable effects on symptoms, exercise capacity and mortality. Growth hormone (GH) and insulin-like growth factor (IGF)-1 are involved in several physiological processes such as the control of muscle mass and function, body composition and regulation of nutrient metabolism. The role of GH and IGF-1 as modulators of myocardial structure and function is well established. Receptors for both GH and IGF-1 are expressed by cardiac myocytes; therefore, GH may act directly on the heart or via the induction of local or systemic IGF-1, while IGF-1 may act by endocrine, paracrine or autocrine mechanisms. Patients with acromegaly have an increased propensity to develop ventricular hypertrophy and cardiovascular diseases; impaired cardiac efficiency can also be observed in patients with GH deficiency. Animal models of pressure and volume overload have demonstrated up-regulation of cardiac IGF-1 production and expression of GH and IGF-1 receptors, implying that the local regulation of these factors is influenced by hemodynamic changes. Moreover, experimental studies suggest that GH and IGF-1 have stimulatory effects on myocardial contractility, possibly mediated by changes in intracellular calcium handling. Heart failure is due to ventricular dilation with inadequate wall thickening that leads to impaired cardiac performance; therefore, based on previous evidence we would expect beneficial effects from the use of GH in these patients. Several papers have highlighted the positive influence of GH in the regulation of heart development and performance. In patients with GH deficiency, GH administration dramatically improves cardiac function. In small open studies, acute and chronic GH treatment has demonstrated beneficial effects in patients with heart failure due to ischemic or idiopathic cardiomyopathy. Recently, two randomized, placebo-controlled studies did not show any significant GH-mediated improvement in cardiac performance in patients with dilated cardiomyopathy, despite significant increases in IGF-1. Acquired GH resistance might be an important feature of severe heart failure and explain the diverse responses to GH therapy observed in different patients. Whether GH treatment will finally find a place in the treatment of heart failure, and with which modalities, remains to be established.
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PMID:Role of growth hormone in chronic heart failure: therapeutic implications. 1111 May 15

Heart failure is an epidemic within the United States and, despite current medical therapy, carries a high mortality rate. Growth hormone and insulin-like growth factor-1 have known direct effects on the cardiovascular system. Improvement in contractility, reduction in wall stress, and increase in cardiac performance have been noted in animal experiments. Furthermore, preliminary data from human trials are encouraging. This report outlines the biology of growth hormone, the experimental and human data to support clinical trials of growth hormone treatment, and the outcome of trials reported to date.
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PMID:Exogenous growth hormone: a new therapy for dilated cardiomyopathy. 1111 52

Growth hormone (GH) has been reported to be useful to treat heart failure. To elucidate whether GH has direct beneficial effects on the heart, we examined effects of GH on oxidative stress-induced apoptosis in cardiac myocytes. TUNEL staining and DNA ladder analysis revealed that hydrogen peroxide (H2O2)-induced apoptosis of cardiomyocytes was significantly suppressed by the pretreatment with GH. GH strongly activated extracellular signal-regulated kinases (ERKs) in cardiac myocytes and the cardioprotective effect of GH was abolished by inhibition of ERKs. Overexpression of dominant negative mutant Ras suppressed GH-stimulated ERK activation. Overexpression of Csk that inactivates Src family tyrosine kinases also inhibited ERK activation evoked by GH. A broad-spectrum inhibitor of protein tyrosine kinases (PTKs), genistein, strongly suppressed GH-induced ERK activation and the cardioprotective effect of GH against apoptotic cell death. GH induced tyrosine phosphorylation of EGF receptor and JAK2 in cardiac myocytes, and an EGF receptor inhibitor tyrphostin AG1478 and a JAK2 inhibitor tyrphostin B42 completely inhibited GH-induced ERK activation. Tyrphostin B42 also suppressed the phosphorylation of EGF receptor stimulated by GH. These findings suggest that GH has a direct protective effect on cardiac myocytes against apoptosis and that the effect of GH is attributed at least in part to the activation of ERKs through Ras and PTKs including JAK2, Src, and EGF receptor tyrosine kinase.
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PMID:Growth hormone signalling and apoptosis in neonatal rat cardiomyocytes. 1168 20


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