Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examines acute changes in circulating levels of atrial natriuretic peptide (ANP) and insulin-like growth factor (IGF-1) during short periods of myocardial ischemia experienced at coronary angioplasty. Ten patients (mean age 55.7 +/- 3.9 years, nine men) undergoing angioplasty to the left anterior descending coronary artery were studied. Angioplasty of the left anterior descending coronary artery was performed with the balloon inflations maintained at 6 to 10 atm for 20 to 90 seconds. Blood was sampled from the coronary sinus for ANP, IGF-1 (both total and free), and lactate levels at (1) after catheterization of the coronary sinus, (2) after the initial left coronary angiography, (3) immediately after balloon deflation, and (4) 5 minutes after deflation. ANP levels (pmol/L +/- SEM) rose significantly at the end of balloon deflation (13.4 +/- 2.8; p < 0.01) compared with baseline levels (8.8 +/- 1.9). This rise was sustained for at least 5 minutes after balloon deflation (13.7 +/- 3.1; p < 0.01). ANP levels were not affected by the injections of angiographic contrast media. Free IGF-1 levels rose after injections of radiographic contrast but not after balloon inflation or deflation. Total IGF-1 levels did not change significantly at any of the sampling times. Lactic acid (mmol/L) levels rose at the end of balloon inflation (2.66 +/- 0.6) compared with baseline (2.13 +/- 0.7; p < 0.05) but returned to normal within 5 minutes of balloon deflation. Neither lactic acid levels nor release of ANP or IGF-1 correlated with the initial left ventricular end-diastolic pressure or the degree of electrocardiographic ST depression during the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute changes in atrial natriuretic peptide, insulin-like growth factor-1, and lactate levels during left anterior descending coronary artery angioplasty. 757 78

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

Low birth weight has been associated with an increased incidence of ischaemic heart disease (IHD) and type 2 diabetes. Endocrine regulation of fetal growth by growth hormone (GH) and insulin-like growth factor (IGF)-I is complex. Placental GH is detectable in maternal serum from the 8th to the 12th gestational week, and rises gradually during pregnancy where it replaces pituitary GH in the maternal circulation. The rise in placental GH may explain the pregnancy-induced rise in maternal serum IGF-I levels. In the fetal compartment, IGF-I levels increase significantly in normally growing fetuses from 18 to 40 weeks of gestation, but IGF-I levels are four to five times lower than those in the maternal circulation. Thus IGF-I levels in fetal as well as in maternal circulation are thought to regulate fetal growth. Circulating levels of IGF-I are thought to be genetically controlled and several IGF-I gene polymorphisms have been described. IGF-I gene polymorphisms are associated with birth weight in some studies but not in all. Likewise, IGF-I gene polymorphisms are associated with serum IGF-I in healthy adults in some studies, although some controversy exists. Serum IGF-I decreases with increasing age in healthy adults, and this decline could hypothetically be responsible for the increased risk of IHD with ageing. A recent nested case-control study found that adults without IHD, but with low circulating IGF-I levels and high IGF binding protein-3 levels, had a significantly increased risk of developing IHD during a 15-year follow-up period. In summary, the GH/IGF-I axis is involved in the regulation of fetal growth. Furthermore, it has been suggested that low IGF-I may increase the risk of IHD in otherwise healthy subjects. Hypothetically, intrauterine programming of the GH/IGF axis may influence postnatal growth, insulin resistance and consequently the risk of cardiovascular disease. Thus IGF-I may serve as a link between fetal growth and adult-onset disease.
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PMID:Intrauterine growth retardation and consequences for endocrine and cardiovascular diseases in adult life: does insulin-like growth factor-I play a role? 1467 11

Cardiomyocyte apoptosis has been associated with the pathogenesis of heart failure as well as ischemic and inflammatory myocardial conditions. The aim of this study is to give a critical synopsis of cardiomyocyte apoptosis and identify methods to prevent or attenuate apoptosis in patients undergoing cardiac surgery. Clinical conditions and agents associated with decreased apoptotic index are early repair or replacement of valvular pathology before deterioration of ventricular function, afterload reduction with medication or intraaortic balloon pulsation in patients with acute increase in afterload or in hemodynamically compromised patients, decreasing catecholamine-induced cardiotoxicity by using beta-blockers, phosphodiesterase inhibitors, or early insertion of intraaortic balloon pulsation or ventricular assist device. Prompt coronary revascularization, which reduces myocardial ischemia time, is the most effective antiapoptotic therapy. Reduction of myocardial apoptosis associated with cardiopulmonary bypass and aortic cross-clamping are other therapeutic targets. Some investigational therapies include ischemic preconditioning and use of antiapoptotic medication such as the caspase inhibitors, antioxidants, calcium-channel blockers, the insulin-like growth factor-1, and the poly-adenosine diphosphate-ribose-synthetase inhibitors. Most of the therapeutic implications in reducing cardiomyocyte apoptosis are still in the experimental phase. Some options are already incorporated in the clinical practice of the cardiovascular surgeon. New therapeutic considerations include avoiding sustained and long-term use of catecholamines and reducing or avoiding cardiopulmonary bypass-when clinically feasible. Noncatecholamine inotropes should be preferred for patients undergoing heart failure surgery and for patients with low output syndrome after open-heart surgery. The lessons learned from apoptosis research reinforce more liberal and early insertion of intraaortic balloon pulsation or ventricular assist device in clinical low output states.
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PMID:Apoptosis: pathophysiology and therapeutic implications for the cardiac surgeon. 1533 71

Studies in animal models of myocardial ischemia-reperfusion revealed that the administration of insulin-like growth factor (IGF-1) can provide substantial cardioprotective effect. However, the mechanisms by which IGF-1 prevents myocardial ischemia-reperfusion injury are not fully understood. This study addresses whether mitochondrial bioenergetic pathways are involved in the cardioprotective effects of IGF-1. Single cardiomyocytes from adult rats were incubated in the absence or presence of IGF-1 for 60 min and subjected to 60 min hypoxia followed by 30 min reoxygenation at 37 degrees C. Mitochondrial function was evaluated by assessment of enzyme activities of oxidative phosphorylation and Krebs cycle pathways. Hypoxia/reoxygenation (HR) caused significant inhibition of mitochondrial respiratory complex IV and V activities and of the Krebs cycle enzyme citrate synthase, whereas pretreatment with IGF-1 maintained enzyme activities in myocytes at or near control levels. Mitochondrial membrane potential, evaluated with JC-1 staining, was significantly higher in IGF-1 + HR- treated myocytes than in HR alone, with levels similar to those found in normal control cardiomyocytes. In addition, IGF-1 reduced both HR-induced lactate dehydrogenase (LDH) release and malondialdehyde production (an indicator of lipid peroxidation) in cardiomyocytes. These results suggest that IGF-1 protects cardiomyocytes from HR injury via stabilizing mitochondria and reducing reactive oxidative species (ROS) damage.
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PMID:Mitochondrial involvement in IGF-1 induced protection of cardiomyocytes against hypoxia/reoxygenation injury. 1726 81

Diabetes mellitus is the most common disease in Westernized countries in large part because of the rising prevalence of obesity and physical inactivity. In addition, diabetes mellitus is an important risk factor for both heart failure and ischemic heart disease. As insulin resistance is known as an important pathophysiological feature in the cardiac diseases, understanding the mechanisms responsible for altered metabolism and insulin signaling in the diabetic heart may help identify novel targets in these conditions. Phosphatidylinositol (PI)-3 kinase (PI3K) and Akt are key signaling molecules in insulin and insulin-like growth factor-1 (IGF-1), which induce multiple biological effects in the heart such as cell survival and hypertrophy. Here, we have shown several fundamental techniques to study the role of PI3K and Akt in heart diseases.
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PMID:Assessment of PI-3 kinase and Akt in ischemic heart diseases in diabetes. 1828 83

Ischemic heart disease is characterized chronically by a healed infarct, foci of myocardial scarring, cavitary dilation, and impaired ventricular performance. These alterations can only be reversed by replacement of scarred tissue with functionally competent myocardium. We tested whether cardiac progenitor cells (CPCs) implanted in proximity of healed infarcts or resident CPCs stimulated locally by hepatocyte growth factor and insulin-like growth factor-1 invade the scarred myocardium and generate myocytes and coronary vessels improving the hemodynamics of the infarcted heart. Hepatocyte growth factor is a powerful chemoattractant of CPCs, and insulin-like growth factor-1 promotes their proliferation and survival. Injection of CPCs or growth factors led to the replacement of approximately 42% of the scar with newly formed myocardium, attenuated ventricular dilation and prevented the chronic decline in function of the infarcted heart. Cardiac repair was mediated by the ability of CPCs to synthesize matrix metalloproteinases that degraded collagen proteins, forming tunnels within the fibrotic tissue during their migration across the scarred myocardium. New myocytes had a 2n karyotype and possessed 2 sex chromosomes, excluding cell fusion. Clinically, CPCs represent an ideal candidate cell for cardiac repair in patients with chronic heart failure. CPCs may be isolated from myocardial biopsies and, following their expansion in vitro, administered back to the same patients avoiding the adverse effects associated with the use of nonautologous cells. Alternatively, growth factors may be delivered locally to stimulate resident CPCs and promote myocardial regeneration. These forms of treatments could be repeated over time to reduce progressively tissue scarring and expand the working myocardium.
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PMID:Local activation or implantation of cardiac progenitor cells rescues scarred infarcted myocardium improving cardiac function. 1855 76

Despite an improvement in the therapeutic strategies available for an acute ischemic event, cardiac disease is still the principal cause of morbidity and mortality in Western societies. A shift from acute towards more chronic heart disease due to atherosclerotic disease has been recognized. Modification of adaptive capacities of the cardiac muscle after damage remains a key component in the prevention of chronic cardiac disease, such as overt heart failure. It has recently been demonstrated that local insulin-like growth factor (IGF)-1 homeostasis in the cardiac tissue is closely involved in postischemic adaptation, such as the process of remodeling. Both experimental and clinical data support the theory that IGF-1 plays a key role in the adaptive response of the myocardium during both acute myocardial ischemia and chronic myocardial failure, regulating left ventricular remodeling and thereby restoring left ventricular architecture. This eventually leads to improvement in the function of the failing heart. While most experimental data support the beneficial role of IGF-1 in restoring architecture and function of the failing heart, clinical trials investigating the role of IGF-1 treatment of patients in cardiac failure show conflicting results. In this bench-to-bedside review, the authors aim to highlight recent advances in knowledge of the role of paracrine and autocrine IGF balances during postischemic cardiac adaptation, in order to present possible new initiatives concerning therapeutic strategies in maladaptive cardiac performance, such as the syndrome of heart failure.
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PMID:The role of insulin-like growth factor during a postischemic period - new insights into pathophysiologic pathways in cardiac tissue. 1980 48

There is increasing awareness that childhood circumstances influence disease risk in adulthood. As well as being strongly influenced by genes/genetic factors, stature acts as a marker for early-life exposures, such as diet, and is associated with risk of several chronic diseases in adulthood. Stature is also a marker for levels of insulin-like growth factor (IGF)-I in childhood. Levels of IGF-I are nutritionally regulated and are therefore modifiable. Milk intake in childhood and in adulthood is positively associated with higher levels of circulating IGF-I and, in children, higher circulating IGF-I promotes linear growth. Studies conducted by our team and others, however, indicate that the effect of milk is complicated because consumption in childhood appears to have long-term, programming effects which are opposite to the immediate effects of consuming milk. Specifically, studies suggest that the long-term effect of higher levels of milk intake in early childhood is opposite to the expected short-term effect, because milk intake in early-life is inversely associated with IGF-I levels throughout adult life. We hypothesize that this long-term programming effect is via a resetting of pituitary control in response to raised levels of IGF-I in childhood. Such a programming effect of milk intake in early life could potentially have implications for cancer and ischemic heart disease risk many years later.
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PMID:Milk and linear growth: programming of the igf-I axis and implication for health in adulthood. 2133 92

The term small for gestational age (SGA) refers to infants whose birth weights and/or lengths are at least two standard deviation (SD) units less than the mean for gestational age. This condition affects approximately 3%-10% of newborns. Causes for SGA birth include environmental factors, placental factors such as abnormal uteroplacental blood flow, and inherited genetic mutations. In the past two decades, an enhanced understanding of genetics has identified several potential causes for SGA. These include mutations that affect the growth hormone (GH)/insulin-like growth factor (IGF)-1 axis, including mutations in the IGF-1 gene and acid-labile subunit (ALS) deficiency. In addition, select polymorphisms observed in patients with SGA include those involved in genes associated with obesity, type 2 diabetes, hypertension, ischemic heart disease and deletion of exon 3 growth hormone receptor (d3-GHR) polymorphism. Uniparental disomy (UPD) and imprinting effects may also underlie some of the phenotypes observed in SGA individuals. The variety of genetic mutations associated with SGA births helps explain the diversity of phenotype characteristics, such as impaired motor or mental development, present in individuals with this disorder. Predicting the effectiveness of recombinant human GH (hGH) therapy for each type of mutation remains challenging. Factors affecting response to hGH therapy include the dose and method of hGH administration as well as the age of initiation of hGH therapy. This article reviews the results of these studies and summarizes the success of hGH therapy in treating this difficult and genetically heterogenous disorder.
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PMID:Genetic factors associated with small for gestational age birth and the use of human growth hormone in treating the disorder. 2258 1


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