Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

31P-NMR spectroscopy has the potential to assess myocardial damage directly and noninvasively by ascertaining the relative abundances of phosphorus-containing compounds relevant to metabolism under stress conditions. Decrease in the PCr/ATP ratio during exercise is an indicator of the level of stress to which the myocardium is subject. This ratio will remain constant under mild to moderate exercise conditions in a healthy subject, but may show a precipitous decrease even under mild exercise when regions of the myocardium are ischemic. The studies examined here indicate that cardiac patients with some forms of ischemia showed a PCr/ATP ratio decrease even under light exercise, while no decrease was observed in patients whose heart disease was known to be nonischemic. Hypertension and nonstenotic chest pain in women can, in some cases, produce a decrease in PCr/ATP ratio. Only the hypertensive patients showed a significant difference in the prestress PCr/ATP ratio when compared with controls. These studies suggest that 31P-NMR spectroscopy before and during mild exercise in the bore of the magnet can be a useful indicator of the presence or absence of an ischemic component to myocardial disorder.
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PMID:The 31P-NMR stress test: an approach for detecting myocardial ischemia. 1114 77

Contractile failure of myocardial cells is a common cause of mortality in ischemic heart disease. In response to hypoxic conditions, cells upregulate the activity of hypoxia-inducible factor 1 (HIF-1) and express a number of genes encoding proteins that either enhance O (2)delivery or increase cellular ATP levels. HIF-1 is a heterodimer of bHLH-PAS proteins, HIF-1 alpha and HIF-1 beta. Both subunits are constitutively expressed under normoxic conditions, but HIF-1 alpha levels are kept low by proteolytic degradation, then stabilized under conditions of low O (2)by a mechanism that is poorly understood. Here we tested the hypothesis that expression of HIF-1 alpha in cardiac cells may be affected by two known cardioprotective agents. We tested l-carnosine, a naturally occurring dipeptide which has been shown to improve myocardial contractility during hypoxia, and verapamil, a calcium channel blocker frequently prescribed for the treatment of heart disease. The levels of HIF-1 alphamRNA remained relatively stable during time course hypoxia (1% O (2)) in H9c2 cardiomyoblasts, then increased slightly after 24 h. In cells pretreated with 1 microM carnosine, the levels of mRNA were transiently reduced, but then increased after 24 h similar to the controls. The levels of HIF-1 alpha protein increased rapidly in H9c2 cells within 30 min of hypoxia, but this induction was significantly reduced in cells treated with either carnosine or verapamil. In addition, treatment of cells with these agents further reduced the low levels of HIF-1 under normoxic conditions. These results suggest that l-carnosine and verapamil may affect the regulated proteolytic degradation of HIF-1 alpha in heart cells during hypoxia.
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PMID:l-carnosine and verapamil inhibit hypoxia-induced expression of hypoxia inducible factor (HIF-1 alpha) in H9c2 cardiomyoblasts. 1188 12

ATP diphosphohydrolase is an enzyme described in platelets and may be related to the control of ADP-dependent platelet aggregation. Platelet aggregation in atherosclerotic coronary arteries, and the release of platelet-derived factors, play an important role in coronary artery disease syndromes. In this study, we determined the activity of ATP diphosphohydrolase in platelets from patients with chronic and acute coronary artery disease syndromes and healthy persons. The following groups were studied: healthy persons (group I), patients with chronic heart disease (group II) and acute heart disease (group III). Results did not demonstrate differences between the groups studied. The control group demonstrated a lower range of enzyme activity. The patients from groups II and III had ingested drugs with actions upon the cardiovascular system and the effect, in vitro, of these drugs upon the ATP diphosphohydrolase activity in human platelets was also investigated. The in vitro experiments demonstrated that 2.0 mM acetylsalicylic acid inhibited ATP hydrolysis by human platelets by approximately 55%. Significant correlation was observed between ADP hydrolysis and glucose blood levels in the control group and between ATP hydrolysis and triglycerides in the group II. These results contribute to our understanding of a possible relationship between ATP diphosphohydrolase and thrombogenesis.
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PMID:ATP diphosphohydrolase in human platelets from patients with coronary arteries heart disease. 1262 46

Sudden death due to nonpenetrating chest wall impact in the absence of injury to the ribs, sternum and heart is known as commotio cordis. Although once thought rare, an increasing number of these events have been reported. Indeed, a significant percentage of deaths on the athletic field are due to chest wall impact. Commotio cordis is most frequently observed in young individuals (age 4-18 years), but may also occur in adults. Sudden death is instantaneous or preceded by several seconds of lightheadedness after the chest wall blow. Victims are most often found in ventricular fibrillation, and successful resuscitation is more difficult than expected given the young age, excellent health of the victims, and the absence of structural heart disease. Autopsy examination is notable for the lack of any significant cardiac or thoracic abnormalities. In an experimental model of commotio cordis utilizing anesthetized juvenile swine, ventricular fibrillation can be produced by a 30 mph baseball strike if the strike occurred during the vulnerable period of repolarization, on the upslope of the T-wave. Energy of the impact object was also found to be a critical variable with 40 mph baseballs more likely to cause ventricular fibrillation than velocities less or greater than 40 mph. In addition, more rigid impact objects and blows directly over the center of the chest were more likely to cause ventricular fibrillation. Peak left ventricular pressure generated by the chest wall blow correlated with the risk of ventricular fibrillation. Activation of the K(+)(ATP) channel is a likely cause of the ventricular fibrillation produced by chest wall blows. Successful resuscitation is attainable with early defibrillation.
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PMID:Mechanically induced sudden death in chest wall impact (commotio cordis). 1273 77

The AMP-activated protein kinase (AMPK) is an alphabetagamma heterotrimer that is activated by low cellular energy status and affects a switch away from energy-requiring processes and toward catabolism. While it is primarily regulated by AMP and ATP, high muscle glycogen has also been shown to repress its activation. Mutations in the gamma2 and gamma3 subunit isoforms lead to arrhythmias associated with abnormal glycogen storage in human heart and elevated glycogen in pig muscle, respectively. A putative glycogen binding domain (GBD) has now been identified in the beta subunits. Coexpression of truncated beta subunits lacking the GBD with alpha and gamma subunits yielded complexes that were active and normally regulated. However, coexpression of alpha and gamma with full-length beta caused accumulation of AMPK in large cytoplasmic inclusions that could be counterstained with anti-glycogen or anti-glycogen synthase antibodies. These inclusions were not affected by mutations that increased or abolished the kinase activity and were not observed by using truncated beta subunits lacking the GBD. Our results suggest that the GBD binds glycogen and can lead to abnormal glycogen-containing inclusions when the kinase is overexpressed. These may be related to the abnormal glycogen storage bodies seen in heart disease patients with gamma2 mutations.
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PMID:A novel domain in AMP-activated protein kinase causes glycogen storage bodies similar to those seen in hereditary cardiac arrhythmias. 1274 36

Theoretical and experimental research data as well as human epidemiological studies on large populations suggest a great difference in influencing cardiovascular processes and alterations among the oral antidiabetic drugs used in the treatment of type II diabetes mellitus. Drugs delaying or inhibiting carbohydrate absorption as well as insulin sensitizers have an unambiguous reducing effect on diabetic cardiovascular complications. Only fluid retention needs precaution during the treatment with thiazolidinedions in patients suffering from heart disease. Among insulin secretizers repaglinid, glibenclamid and glipizide have an ATP-sensitive potassium channel inhibiting effect in the vascular smooth muscle cells, too, reducing hereby vasodilation. Glibenclamide also inhibits ischaemic preconditioning. Therefore, the antidiabetic drug of choice can be decisive in diabetic patients suffering from ischaemic heart diseases or peripheral obliterative disorders. In the case of secondary sulphonylurea resistance and/or severe ischaemic alterations insulin treatment becomes necessary to avoid further cardiovascular complications.
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PMID:[Oral antidiabetic therapy and cardiovascular complications: theoretical problem or clinical evidence?]. 1279 25

ATP-sensitive K(+) (KATP) channels are present on the sarcolemma (sarcKATP channels) and mitochondria (mitoKATP channels) of cardiac myocytes. Amiodarone, a class III antiarrhythmic drug, reduces sudden cardiac death in patients with organic heart disease. The objective of the present study was to investigate the effects of amiodarone on sarcKATP and mitoKATP channels. Single sarcKATP channel current and flavoprotein fluorescence were measured in guinea pig ventricular myocytes to assay sarcKATP and mitoKATP channel activity, respectively. Amiodarone inhibited the sarcKATP channel currents in a concentration-dependent manner without affecting its unitary amplitude. The IC50 values were 0.35 microM in the inside-out patch exposed to an ATP-free solution and 2.8 microM in the cell-attached patch under metabolic inhibition, respectively. Amiodarone (10 microM) alone did not oxidize the flavoprotein. In addition, the oxidative effect of the mitoKATP channel opener diazoxide (100 microM) was unaffected by amiodarone. Exposure to ouabain (1 mM) for 30 min produced mitochondrial Ca(2+) overload, and the intensity of rhod-2 fluorescence increased to 246 +/- 16% of baseline (n = 9). Amiodarone did not alter the ouabain-induced mitochondrial Ca(2+) overload (236 +/- 10% of baseline, n = 7). Treatment with diazoxide significantly reduced the ouabain-induced mitochondrial Ca(2+) overload (158 +/- 15% of baseline, n = 8, p < 0.05 versus ouabain); this effect was not abolished by amiodarone (154 +/- 10% of baseline, n = 8, p < 0.05 versus ouabain). These results suggest that amiodarone inhibits sarcKATP but not mitoKATP channels in cardiac myocytes. Such an action of amiodarone may effectively prevent ischemic arrhythmias without causing ischemic damage.
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PMID:Amiodarone inhibits sarcolemmal but not mitochondrial KATP channels in Guinea pig ventricular cells. 1453 61

The ATP III report represents an important advance from previous ATP reports dating back to the late 1980s. The guidelines are more tightly evidence-based than previous reports, partly because of evolution of the guideline process, requiring clearly delineated links between evidence and recommendations and also because of the robust evidence base published over the last decade. An important change in ATP III is the expansion of the high-risk category to include patients without evident vascular disease, but with a level of risk equivalent to those patients with established CHD. This group termed "coronary heart disease equivalents" now includes patients with diabetes, and those with a 10-year absolute risk of over 20 percent for CHD events. With the ATP III report, the Framingham risk score is formally introduced into the guideline process. The scoring system allows for easy calculation of the absolute risk for an individual of having a "hard" CHD event (myocardial infarction, or CHD death). The report also discusses in detail concepts of lifetime or long-term risk. ATP III has broadened recommendations for lifestyle change termed "therapeutic lifestyle change (TLC)," and eliminated the step 1 and step 2 diet approach. Finally, the report details established approaches to improve adherence and provides patients and clinicians with a set of implementation tools to enhance use of the guidelines and compliance with the guidelines' recommendations. It is hoped that by improved understanding, recognition of a firm evidence base, and education through multiple channels, that adherence with the new ATP III guidelines will improve the care of our population by more effectively targeting lipid factors that lead to the development and progression of atherosclerotic cardiovascular disease.
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PMID:Report of the Adult Treatment Panel III: the 2001 National Cholesterol Education Program guidelines on the detection, evaluation and treatment of elevated cholesterol in adults. 1462 53

The purpose of this cross-sectional analysis is to examine modifiable CVD risk factors in relation to menopausal status, age, and length of residence in the U.S. of midlife women from the former Soviet Union. The analysis includes baseline data for 193 women, aged 40-70, who lived in the U.S. fewer than 8 years and were enrolled in an ongoing four-year study of post-immigration health and behavior change. Data collection was conducted in women's homes or other community locations. The presence of seven health risk indicators (obesity, dyslipidemia, high blood pressure, diabetes mellitus, sedentary lifestyle, smoking, and excessive alcohol use) was assessed. In addition, Framingham 10 year risk scores for heart disease, and the presence of metabolic syndrome, were calculated using recent National Cholesterol Education Program (ATP-III) guidelines. Consistent with the age distribution, 60% of the women were postmenopausal. Four risk indicators (obesity, dyslipidemia, high blood pressure, and sedentary lifestyle) were identified as significant areas of concern. Although the Framingham risk scores did not seem excessively high, almost 25% of the women had metabolic syndrome. Older and postmenopausal women had significantly higher scores on all risk estimates. When age and menopausal status were held constant, menopausal status remained an independent contributor for the number of CVD risk indicators. Issues specific to this group of women because of their pre- and post-migration lifestyles are discussed in relation to their CVD risk status.
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PMID:Cardiovascular disease risk factors and menopausal status in midlife women from the former Soviet Union. 1466 3

Hemochromatosis is a hereditary iron overload syndrome characterized by increased iron storage, followed by liver cirrhosis and is often associated with restrictive cardiomyopathy. The purpose of this study was to detect alterations of cardiac high-energy phosphate metabolism in patients with hereditary hemochromatosis (HHC) prior to the development of structural heart diseases. Therefore cardiac phosphorus-31 two-dimensional chemical shift imaging ((31)P 2D CSI) was employed. Twenty-four male patients (mean age 47.2 +/- 12 years) homozygous for the C282Y mutation in the hemochromatosis associated HFE gene and twenty-four male healthy volunteers (mean age 47 +/- 11 years) as age-matched controls were included in this study. Using a 1.5-Tesla whole-body magnetic resonance scanner, electrocardiograph-triggered transversal 31P 2D CSI was performed. Left ventricle mean phosphocreatine (PCr) to beta-adenosine triphosphate (beta-ATP) ratios of patients with HHC (1.60 +/- 0.41) were significantly decreased in comparison to healthy volunteers (1.93 +/- 0.36; p = 0.004). Furthermore, we detected moderate, negative correlations between left ventricular PCr to beta-ATP ratios and transferrin saturation, cholesterol, low-density lipoprotein as well as triglyceride. This study shows that 31P 2D CSI permits the detection of alterations of cardiac high-energy phosphate metabolism in patients with HHC, but without any evidence for heart disease. The decreased PCr to beta-ATP ratios in HHC might be caused by mitochondrial impairment due to cardiac iron overload.
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PMID:Cardiac phosphorus-31 two-dimensional chemical shift imaging in patients with hereditary hemochromatosis. 1512 Jan 71


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