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

To determine whether additional hypertrophy would be beneficial or maladaptive in cardiac failure, the effects of insulin-like growth factor (IGF-1) were investigated in rats with left ventricular (LV) dysfunction. In normal rats, 3 mg/kg per d of recombinant human IGF-1 for 14 d augmented LV wt (32%) and increased LV/body wt ratio (P < 0.01). 2 d after coronary occlusion, rats were randomized to IGF-1 (3 mg/kg per d) or placebo. After 2 wk, IGF-1-treated rats showed significant increases in LV wt (13%) and LV wt/tibial length ratio, but LV/body wt ratio was unchanged. By microangiography, compared with controls (n = 12) IGF-1-treated rats (n = 16) showed increased LV end-diastolic volume (19%) and stroke volume (31%) (both significant normalized to tibial length, but not to body wt). Average infarct size did not differ between groups. The LV ejection fraction (EF) was not significantly different between groups, but estimated cardiac output was higher in treated rats; there was a significant interaction for the EF between infarct size and treatment (P = 0.029) and a trend for EF to be higher in treated rats with large infarctions (EF 33.4 vs 25.1% in controls). Myocyte cross-sectional areas in noninfarcted LV zones tended to be larger in treated rats (232.1 vs 205.4 microns 2; P = 0.10), but there was no difference in capillary density and collagen content did not differ between groups. In conclusion, IGF-1 administration caused hypertrophy of the normal heart in vivo. When stimulated by IGF-1, the severely dysfunctional heart in evolving myocardial infarction is capable of undergoing additional hypertrophy with evidence of improved function, suggesting a beneficial effect. Further investigation of the potential role of growth factor therapy in heart failure appears warranted.
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PMID:Insulin-like growth factor-1 enhances ventricular hypertrophy and function during the onset of experimental cardiac failure. 786 Jul 46

The effects of growth hormone (GH) plus insulin-like growth factor-1 (IGF-1) were tested in an experimental model of cardiac failure treated with chronic angiotensin-converting enzyme (ACE) inhibition. Myocardial infarction was induced in rats by left coronary artery ligation. Two weeks after ligation, the animals received either captopril (2 g/L in drinking water) or water for 3 months. The rats were then given either GH (2 mg/kg/day) plus IGF-1 (2 mg/kg/day) or vehicle for 14 days. Captopril treatment decreased mean arterial pressure (MAP), left ventricular end-diastolic pressure (LVEDP) and systemic vascular resistance (SVR) (p < 0.05), and increased cardiac index (CI) and stroke volume index (SVI) (p < 0.05). GH/IGF-1 or captopril+GH/IGF-1 treatment decreased MAP, LVEDP, and SVR (p < 0.05), and increased left ventricular maximum dP/dt, CI, and SVI (p < 0.05). The increases in CI and SVI were significantly greater in the captopril+GH/IGF-1-treated animals than in those treated with captopril alone (p < 0.05). The beneficial effect of captopril in reducing cardiac hypertrophy was preserved in the captopril+GH/IGF-1 group. The results indicate that GH/IGF-1 and captopril can improve cardiac performance in congestive heart failure by independent and complementary mechanisms.
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PMID:Beneficial effects of growth hormone and insulin-like growth factor-1 in experimental heart failure in rats treated with chronic ACE inhibition. 858 84

To determine whether the attenuation in the growth capacity of myocytes in the overloaded aging heart is associated with an impairment in the activation of insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) in the stressed cells, large myocardial infarcts were produced in Fischer 344 rats at 4 and 16 months of age, and the animals were killed 6 hours, 3 days, and 7 days later. After the documentation of cardiac failure, the unaffected myocytes were enzymatically dissociated, and the expression of IGF-1 and IGF-1R was measured at these three time points after surgery. The level of expression of IGF-1R mRNA increased at 3 days and remained elevated at 7 days in both age groups. In addition, an increase in IGF-1R protein in these cells was found, with no apparent difference with age. This phenomenon was coupled with an upregulation of IGF-1 mRNA of comparable magnitude in the younger and older animals. In contrast, the increases in the dimensional properties of myocytes were delayed and of smaller magnitude in the older infarcted rats. Moreover, the expression of atrial natriuretic factor, used as a molecular marker of myocyte cellular hypertrophy, was greater at 3 days in 4-month-old rats and at 7 days in 16-month-old rats. Thus, aging may affect the hypertrophic response of myocytes after infarction but has no impact on the ability of the cells to enhance the expression of IGF-1 and IGF-1R, which may sustain only in part the growth reserve mechanisms of the pathological heart.
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PMID:Aging does not affect the activation of the myocyte insulin-like growth factor-1 autocrine system after infarction and ventricular failure in Fischer 344 rats. 863 10

Previous studies showed increased growth hormone (GH) plasma levels in patients with severe heart failure. It has been hypothesized that the activation of adenohypophysis determines the enhanced release of GH. The present study was designed to verify whether impaired hepatic function, due to biventricular cardiac failure and hepatic stasis, by reducing synthesis and release of insulin-like growth factor-1 (IGF-1), may affect the negative feedback mechanism of the IGF-1 on GH secretion. We studied 20 normotensive, non diabetic patients without primitive liver disease; 10 patients in NYHA functional class IV with clinical signs of biventricular cardiac impairment and hepatic stasis (Group A); 10 patients in NYHA functional class III with prevalent left ventricular dysfunction (Group B). Blood samples for radioimmunologic determination of GH, IGF-1, atrial natriuretic factor (ANF), proteins, albumin plasma levels and transaminase plasma levels measurements, were collected 24 hours before hemodynamic study. Group A patients had clinical and hemodynamic signs of hepatic stasis with impaired liver function (SGOT 68 +/- 5.5 U/l; SGPT 89 +/- 4.3 U/1; proteins 4.56 +/- 0.4 g/dl with albumin/globulin ratio < 1; albumin plasma levels 2.8 +/- 0.7 g/dl). The parameters were normal in Group B (SGOT 16 +/- 3.7 U/l;SGPT 13 +/- 1.9 U/l; proteins 7.5 +/- 0.7 g/dl with albumin/globulin ratio > or = 1.5;albumin plasma levels 4.2 +/- 1.2 g/dl). ANF values, over normal range in both groups, were significantly higher in Group A (157.9 +/- 43.9 vs 65.6 +/- 14.6 fmol/ml.p < 0.0001). In Group A GH values were increased (4.9 +/- 4.5 vs 0.12 +/- 0.04 ng/ml); on the contrary IGF-1 values were lower (187.9 +/- 98.2 vs 260.4 +/- 141.4 ng/ml, p < 0.01). The comparison between IGF-1 and albumin plasma levels showed a high correlation either in Group A (r = 0.88, p < 0.001;) or in Group B (r = 0.81, p < 0.001). Our findings allow to hypothesize that the reduced hepatic synthesis and release of IGF-1 may be responsible for the lack of trophic action of GH on cardiac myocytes in patients with biventricular heart failure and hepatic stasis.
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PMID:[Changes in growth hormone/insulin-like growth factor-1 axis in patients with normal pituitary function and biventricular cardiac failure and hepatic stasis]. 876 34

Accumulating evidence suggests from experimental and clinical studies beneficial effects of growth hormone (GH) on contractility, although concomitant cardiac hypertrophy, generally considered to be a cardiovascular risk factor, has also been reported. In the present study, we combine a rat model with impaired cardiac performance after myocardial infarction (MI) with echocardiographic evaluation of GH effects on cardiac structure and function. We have used a rat model with ligation of the left coronary artery in normal, growing male rats resulting in subsequent impaired cardiac performance. After 6 weeks' recovery, blind transthoracic echocardiography was performed to determine infarction size, cardiac geometry and performance. Rats with no signs of myocardial infarction were excluded from the study. After randomization, the rats were treated with daily s.c. injections of saline (n = 8) or recombinant human growth hormone (rhGH) (n = 6) at a dose of approximately 1 mg kg-1 body weight for 1 week. A new blind echocardiography examination was performed after treatment demonstrating a 13% increase in ejection fraction (EF) and a 50% increase in cardiac index in GH-treated rats compared with control rats (P < 0.01). Moreover, GH caused a significant decrease in end-systolic volume. There were no significant changes in left ventricular (LV) or interventricular wall thickness, LV dimensions, heart rate or diastolic function. No effects were seen on LV weight, cardiac insulin-like growth factor (IGF) I, IGF-I receptor and GH receptor mRNA content. GH in a physiological dose improves systolic function in an experimental model of heart failure without signs of hypertrophy, suggesting a potential role as a therapeutic agent in the treatment of heart failure and merits further investigation.
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PMID:Growth hormone improves cardiac function in rats with experimental myocardial infarction. 922 33

End-stage renal disease (ESRD) patients, whether they are treated with hemodialysis or continuous ambulatory peritoneal dialysis, frequently suffer from protein-energy malnutrition, which is associated with increased morbidity and mortality. The protein requirements in dialysis patients are increased compared to those of healthy individuals and nondialyzed patients with chronic renal failure. The intake of protein and energy is frequently reduced because of the underlying disease, comorbidity, psychosocial factors, and uremic anorexia (underdialysis). There are several factors in ESRD patients that may enhance protein catabolism and increase protein requirements, such as low energy intake, amino acid abnormalities, metabolic acidosis, endocrine abnormalities (insulin resistance, hyperglucagonemia, hyperparathyroidism, insensitivity to growth hormone and insulin-like growth factor-1, cardiac failure, infection and inflammation, anemia, and physical inactivity. The dialytic procedures per se may enhance protein catabolism due to dialytic losses of protein and amino acids and, in hemodialysis, an inflammatory response to blood-dialyzer interaction. The relative importance of the various factors which cause anorexia and stimulate protein catabolism is still not well understood.
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PMID:Factors contributing to catabolism in end-stage renal disease patients. 939 22

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

This study aimed to elucidate changes in respiratory muscles and their mechanism in cardiomyopathy. The contractile properties and histology of the diaphragm, as well as serum levels of insulin-like growth factor (IGF)-1, were examined in 10 hamsters with idiopathic dilated cardiomyopathy (CM) and 10 controls. At 28 weeks, body weight in CM was reduced compared with controls (114+/-10 versus 144+/-14 g, p<0.0001). The ratio of diaphragm to body weight was significantly higher in CM than in controls (0.228+/-0.015 versus 0.182+/-0.017, p<0.0001). In vitro, maximal diaphragmatic twitch (303+/-63 versus 455+/-119 g x cm(-2)) and tetanic tensions (1,555+/-369 versus 2,204+/-506 g x cm(-2)) were significantly lower in CM than in controls (p<0.005). The half-relaxation time was significantly shorter in CM (19+/-1 ms) than in controls (24+/-3 ms, p<0.0005). Fatiguability at 25 Hz was significantly less in CM (28%) than in controls (42%, p<0.0001). Diaphragm and gastrocnemius adenosine triphosphatase staining showed type I fibre atrophy in CM, associated with an increase in the number of type I fibres in the diaphragm. Histological examination of both muscles revealed an abnormal muscular pattern. Finally, serum levels of IGF-1 were 47% lower in the CM group than in controls (p<0.0001) and were clearly related to the changes in the contractile properties and histology of the diaphragm. In conclusion, cardiomyopathy in hamsters: 1) depressed the force-generating capacity and shortened the relaxation of the hamster diaphragm; 2) induced type I fibre atrophy in combination with a myopathic pattern; and 3) was associated with a significant reduction in serum levels of insulin-like growth factor-1, related to the diaphragmatic changes. Whether these changes are primary myopathic or secondary to heart failure remains to be elucidated.
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PMID:Effects of dilated cardiomyopathy on the diaphragm in the Syrian hamster. 1006 87

There is now little doubt that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) play a role in cardiac development and in cardiovascular physiology in adult life. Congenital lack of GH is associated with defective cardiac growth, ventricular wall thinning, and impaired systolic function. These abnormalities limit exercise capacity and contribute to the poor quality of life in patients with GH deficiency. In addition, studies with in vitro muscle preparations have shown that IGF-1 affects myocardial contractility by a direct mechanism. These findings suggested that GH would benefit patients affected by heart failure. Indeed, GH and/or IGF-1 have proven beneficial in various models of experimental heart failure. Tested in patients with classes II-IV heart failure, they improved cardiac performance and clinical status. These effects were associated with improved myocardial energetics and de-activation of the neurohormonal system. Because of the uncontrolled nature of the studies and the small number of cases examined, conclusions as to the effectiveness of GH and IGF-1 must await the results from larger trials.
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PMID:Growth hormone: a new therapy for heart failure? 1008 93

Until a few years ago, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) were considered essential only to the control of linear growth, glucose homeostasis, and for the maintenance of skeletal muscle mass. A large body of evidence recently coming from animal and human studies has unequivocally proven that the heart is a target organ for the GH/IGF-1 axis. Specifically GH exerts both direct and indirect cardiovascular actions. Among the direct effects, the ability of GH to trigger cardiac tissue growth plays a pivotal role. Another direct effect is to augment cardiac contractility, independent of myocardial growth. Direct effects of GH also include the improvement of myocardial energetics and mechanical efficiency. Indirect effects of GH on the heart include decreased peripheral vascular resistance (PVR), expansion of blood volume, increased glomerular filtration rate, enhanced respiratory activity, increased skeletal muscle performance, and psychological well-being. Among them, the most consistently found is the decrease of PVR. GH may also raise preload through its sodium-retaining action and its interference with the hormonal system that regulates water and electrolyte metabolism. Particularly important is the effect of GH on skeletal muscle mass and performance. Taking into account that heart failure is characterized by left ventricular dilation, reduced cardiac contractility, and increase of wall stress and peripheral vascular resistance, GH may be beneficial for treatment of heart failure. Animal studies and preliminary human trials have confirmed the validity of the GH approach to the treatment of heart failure. Larger placebo-controlled human studies represent the main focus of future investigations.
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PMID:Growth hormone and the heart. 1020 60


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