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)

A possible cause of the coronary endothelial injury that occurs with ischemia and reperfusion is the local accumulation of leukocytes during these events. To investigate the role of leukocytes in coronary endothelial injury, we tested the effect of leukocyte removal by filtering on coronary endothelial function in a canine model of regional myocardial ischemia and reperfusion. Blood was supplied to the left anterior descending and circumflex arteries of anesthetized dogs via an extracorporeal circulation. A 60-minute left anterior descending occlusion was followed by 120 minutes of reperfusion either with (n = 6) or without (n = 6) leukocyte filters in the extracorporeal circuit. Regional myocardial blood flow was measured with radiolabeled microspheres. Radiolabeled autologous transferrin (113mIn) and erythrocytes (99mTc) were given intravenously during reperfusion for assessment of microvascular permeability. Left anterior descending and circumflex coronary artery rings were assessed in vitro for endothelium-dependent dilation to acetylcholine, ADP, and thrombin. In unfiltered dogs, ischemia and reperfusion increased the protein leak index of ischemic myocardium 2.3-fold compared with that of nonischemic myocardium (2.3 +/- 0.5 to 5.2 +/- 1.6, p less than 0.05). In filtered dogs, there was no difference in the protein leak index of nonischemic versus ischemic myocardium (1.5 +/- 0.4 versus 1.9 +/- 0.5, p = NS). There was impaired left anterior descending coronary artery relaxation (versus circumflex) in response to endothelium-dependent vasodilators in vitro. However, relaxation was not consistently improved by leukocyte filtering. We conclude that leukocytes are responsible for the endothelial injury secondary to ischemia and reperfusion in the coronary microvasculature but have little or no effect on the endothelial injury in epicardial coronary arteries.
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PMID:Role of leukocytes in coronary vascular endothelial injury due to ischemia and reperfusion. 195 76

The antioxidative system (AOS) ceruloplasmin-transferrin (Cp-Tr) was studied by means of electron paramagnetic resonance in 14 rabbits with experimental atherosclerosis and in 33 patients with ischemic heart disease (IHD). A correlation was found between the AOS Cp-Tr activity and the pathological process severity: mild disease was associated with high AOS activity, while in severe disease course, this activity was threefold lower. This regularity was detectable both in experimental animals and in human IHD patients. It was found that hemosorption (HS) exerted a positive effect only in the presence of low AOS Cp-Tr activity which increased after HS in these cases. In high AOS activity HS caused deterioration of the patients' condition and accumulation of lipid peroxidation products in the blood plasma; this was attended with lowering of the AOS Cp-Tr activity.
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PMID:[Ceruloplasmin-transferrin antioxidant system in in experimental and clinical atherosclerosis]. 229 27

Contractile dysfunction of viable, previously ischemic stunned myocardium is thought to be due to reactive oxygen species generated during ischemia/reperfusion. Direct in vivo evidence that oxidants cause systolic or diastolic dysfunction of viable myocardium has, however, been lacking. We sought to determine whether in vivo exposure of canine myocardium to exogenously generated reactive oxygen species could--in the absence of myocardial ischemia or necrosis--"mimic" the depressed systolic contractile function, paradoxical contraction during early diastole, and prolonged diastolic relaxation time characteristic of stunned myocardium. Anesthetized open-chest dogs were randomly assigned to receive either (1) the free radical generating substrates xanthine oxidase + purine + iron-saturated transferrin or (2) saline, infused directly into an anterior coronary vein. Infusion of free radical substrates did not cause ischemia: regional myocardial blood flow and myocardial high-energy phosphate stores were normal in both groups. Furthermore, infusion of xanthine oxidase + purine + transferrin was not associated with histologic or electron microscopic evidence of myocyte injury or death in this model. Xanthine oxidase + purine + transferrin did, however, produce marked abnormalities in regional systolic contractile function; at 2 hours after the onset of infusion, segment shortening (assessed by sonomicrometry) in the perfused region of the heart averaged 62 +/- 5% of baseline, preinfusion values in animals infused with free radical substrates versus 113 +/- 8% of baseline values in saline-administered control dogs (p less than 0.004). This systolic dysfunction was effectively reversed by administration of the free radical scavenging agents superoxide dismutase + catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo infusion of oxygen free radical substrates causes myocardial systolic, but not diastolic dysfunction. 232 2

In recent years, several laboratories have suggested that serum levels of antioxidant activity and redox balance are reduced in patients with chronic renal failure. Some clinical reports have also proposed that defective serum antioxidative enzymes may contribute to a certain uremic toxicity through peroxidative cell damage. A 48-year-old woman was referred to us from the surgical department of our hospital because of consciousness disturbance, pancytopenia and acute acceleration of chronic azotemia after postoperative radiation therapy. We diagnosed acute acceleration of chronic renal failure with severe acidemia and started hemodialysis therapy immediately. Two days after admission to our department, she developed upper abdominal sharp pain and bradyarrhythmia. Serum amylase activity was elevated markedly and the ECG finding showed myocardial ischemia. On the 24th hospital day these complications were treated successfully with conservative therapy and hemodialysis. We considered that radiation therapy in this patient with chronic renal failure evoked marked oxidative stress and that deficiency of transferrin played an important role in peroxidative cell damage.
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PMID:[A case of multiple organ failure induced by postoperative radiation therapy probably evoking oxidative stress]. 769 60

Asian patients with diabetes have a higher prevalence of renal disease than their European counterparts. The aim of the study was to investigate the pattern of the renal excretion of proteins in 70 Asian and 70 European patients with diabetes and to relate it to dietary intake of protein and prevalence of diabetic complications. Compared with matched Europeans, Asian patients had an increased urinary excretion of albumin and transferrin (p < 0.02) with 14 Asians and 6 Europeans having significant microalbuminuria (> 30 micrograms min-1). In 12 Asians and all 6 Europeans this was associated with complications from diabetes, particularly vascular. Asian patients had significantly more ischaemic heart disease (p < 0.001) but less neuropathy (p < 0.001) and retinopathy (p < 0.05) than their matched European counterparts. Asian diets were lower in protein (median (range) Asian vs European: 12.5% (6-29%) vs 19% (11-27%); p < 0.01) and carbohydrate but higher in fat than European diets. There was no correlation between dietary protein intake and excretion of any of the urinary proteins measured. However, a significant correlation was found in Asians between protein intake and length of residence in the UK (p < 0.005). Unless ways to reduce complications can be found then future allocation of resources will need to take this into consideration in areas with large Asian communities.
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PMID:Higher levels of microproteinuria in Asian compared with European patients with diabetes mellitus and their relationship to dietary protein intake and diabetic complications. 818 Dec 50

Regulation of iron balance is of particular interest, especially iron absorption, cellular iron metabolism and transferrin-transferrin receptor in hematopoiesis. Recent advances in molecular and cell biology have helped to reveal the mysteries of cellular iron metabolism concerning mRNA encoding ferritin and transferrin receptor synthesis. The physiology of transferrin and transferrin receptor is applied in the evaluation of erythropoiesis, i.e., erythron transferrin uptake in ferrokinetics and measurement of serum transferrin receptor. In iron absorption, much of the key mechanism remains unknown. The importance of iron metabolism in human beings is discussed in traditional areas of iron deficiency and nutrition. Iron overload is a new clinical problem to be solved in hemochromatosis or in relation to ischemic heart disease.
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PMID:Overview of iron metabolism. 858 65

To investigate whether urinary excretion of transferrin (uTf) and albumin (uAlb) is related to diabetic macroangiopathy, we compared the levels of uTf and uAlb between ischemic heart disease (IHD) group and non-IHD group in patients with non-insulin-dependent diabetes mellitus. The patients (n = 102) without macroproteinuria were enrolled in the present study. Firstly, we divided the subjects into the two groups, IHD group (n = 16) and non-IHD group (n = 86), according to findings of ischemic changes on electrocardiogram. The levels of uTf and uAlb in IHD group were 3.9 +/- 0.9 and 40.6 +/- 9.7 (mean +/- S.E.M.) mg/g Creatinine, respectively. These values were significantly (P < 0.01) higher than those of non-IHD group (1.8 +/- 0.2 for uTf and 19.6 +/- 1.8 for uAlb). There was no significance in the levels of HbA1c, blood pressure, plasma lipids, and diabetic duration between the two groups. Secondly, we divided the subjects by the levels of uTf and uAlb. The frequency of IHD in the group (n = 22, 36.4%) with microalbuminuria and microtransferrinuria was significantly (P <0.03) higher than those (n = 38, 10.5%) with normoalbuninuria and microtransferrinuria, and also significantly (P < 0.02) higher than those (n = 42, 9.5%) with normoalbuminuria and normotransferrinuria. We concluded that the measurement of uAlb is important when approaching diabetic macroangiopathy.
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PMID:Microalbuminuria is closely related to diabetic macroangiopathy. 1041 38

Excessive body iron or iron overload occurs under conditions such as primary (hereditary) hemochromatosis and secondary iron overload (hemosiderosis), which are reaching epidemic levels worldwide. Primary hemochromatosis is the most common genetic disorder with an allele frequency greater than 10% in individuals of European ancestry, while hemosiderosis is less common but associated with a much higher morbidity and mortality. Iron overload leads to iron deposition in many tissues especially the liver, brain, heart and endocrine tissues. Elevated cardiac iron leads to diastolic dysfunction, arrhythmias and dilated cardiomyopathy, and is the primary determinant of survival in patients with secondary iron overload as well as a leading cause of morbidity and mortality in primary hemochromatosis patients. In addition, iron-induced cardiac injury plays a role in acute iron toxicosis (iron poisoning), myocardial ischemia-reperfusion injury, Friedreich ataxia and neurodegenerative diseases. Patients with iron overload also routinely suffer from a range of endocrinopathies, including diabetes mellitus and anterior pituitary dysfunction. Despite clear connections between elevated iron and clinical disease, iron transport remains poorly understood. While low-capacity divalent metal and transferrin-bound transporters are critical under normal physiological conditions, L-type Ca2+ channels (LTCC) are high-capacity pathways of ferrous iron (Fe2+) uptake into cardiomyocytes especially under iron overload conditions. Fe2+ uptake through L-type Ca2+ channels may also be crucial in other excitable cells such as pancreatic beta cells, anterior pituitary cells and neurons. Consequently, LTCC blockers represent a potential new therapy to reduce the toxic effects of excess iron.
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PMID:Role of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy. 1660 32

Ethanol is a molecule of enduring research interest because its consumption has important social as well as medical implications. With excessive ethanol consumption, there is higher prevalence for hypertension, stroke, cardiomyopathy, and arrhythmias. A principal mechanism by which ethanol exerts these cardiovascular effects is through modulation of blood pressure. In this article, we focus on recent research that pursues information on the effects of alcohol on blood pressure in human subjects, regardless of whether they have hypertension or not. Known means by which alcohol exerts hemodynamic effects are briefly covered, and insights on novel biomediators, such as endothelin and gene-based mechanisms, are presented. Newer tools, such as the Alcohol Use Disorders Identification Test-Consumption Questions (AUDIT-C) survey and carbohydrate-deficient transferrin (CDT) serum test, are also covered. Reducing excessive alcohol intake can produce a reduction in blood pressure of up to 4 mm Hg, on average, which could substantially affect the rates of stroke and ischemic heart disease.
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PMID:Alcohol and its relationship to blood pressure. 1688 66

Myocardium reperfusion following coronary artery bypass grafting (CABG) may result in "reperfusion injury" by free radical generations. Since desferrioxamine administration attenuates this syndrome, non-transferrin-bound-iron (NTBI) released into the perfusing medium during CABG was implicated as a catalyst for oxygen radical formation. From 13 patients with "redo" CABG, specimens were collected from the coronary sinus (influx) and the aortic vent (efflux) after each distal coronary anastomosis. Specimens were subjected to sieving chromatography, and fractions were analyzed for total iron and NTBI using atomic absorption spectrometry (AAS). A statistically significant increase in NTBI was measured in influx (p = 0.002) and efflux samples (p = 0.023) collected after each graft. The combined amount of NTBI measured in these specimen was proportional to the CK-MB increase measured in the patients' sera on the day of surgery and the subsequent day. NTBI which accumulated in the circulatory bypass fluid during CABG may catalyze the generation of free radicals in the myocardium when body temperature is restored. This may aggravate myocardial damage as reflected by a post-surgical increase in CK-MB concentrations. Studies are in progress to develop new methods for the removal of NTBI during cardiac surgery. Tissue injury occurs with reperfusion during ischemia. This has been attributed to oxygen-derived free radicals that are generated by substances released from hypoxic areas (Kloner, Przyklenk et al., 1989; McCord, 1998). Reperfusion injury, i.e. the "reperfusion syndrome," occurs after coronary artery bypass grafting (CABG) when the ischemic myocardium is again provided with a supply of blood. Its most serious manifestations are arrhythmia and myocardial stunning (Ar"Rajab, Dawidson et al., 1996; Ferrari, Ceconi et al, 1996). The role of iron in reperfusion injury has been implicated by indirect evidence: during the reperfusion syndrome, the binding of iron with the chelator desferrioxamine (Ambrosio, Zweier et al., 1987; Bel, Martinod et al., 1996), or the administration of exogenous apo-transferrin, improved cardiac contractility and delayed manifestations of cardiac injury (Tiede, Sareen et al., 1990). Iron, as a transition metal, is able to catalyze free radical formation when released into the circulation from endogenous stores as non-transferrin-bound-iron (NTBI). This iron may be bound to small proteins or inorganic ligands (Halliwell and Gutteridge, 1984; Pollock and Campana, 1980; Zweier, 1992). A method for the measurement of NTBI was recently developed (Ambrus, Stadler et al., 1999). The purpose of this study was to explore whether a correlation exists among (a) the amount of NTBI released during CABG surgery, (b) the length of time of myocardial ischemia, and (c) the myocardial damage that occurs during cardiopulmonary bypass.
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PMID:Myocardial release of non-transferrin-bound iron during cardio-pulmonary bypass surgery. 1731 69


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