Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myoglobin is the oxygen-binding protein characteristic of skeletal and cardiac muscle. With muscle disease or dysfunction, myoglobin may enter the circulation, and after renal clearance, it may also appear in the urine. Therefore, the presence of myoglobinemia and myoglobinuria may serve as indicators of the presence and severity of muscle disease. With newly developed methods of detection, myoglobinemia and myoglobinuria are now recognized as complications of trauma, ischemia, surgery, states of exertion and stress, metabolic abnormalities, inherited enzyme disorders, toxin and drug actions, and inflammatory states. Infarction of the heart muscle also can be detected by myoglobin assay. Persistent myoglobinuric states may be complicated by renal failure and electrolyte imbalance. The diagnosis of myoglobinemia and myoglobinuria can be now confirmed with the use of immunoassay techniques. Although not yet widely available, they offer the possibility of the specificity and sensitivity needed for clinical use.
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PMID:Myoglobin: methods and diagnostic uses. 40 72

A normal single left coronary artery was found in a high school boy who died suddenly after Rugby football practice. He had an infarct lesion in the posterior wall where there was no perfusion because of the absence of the right coronary artery. There was no significant lesion in the anterior wall except for contraction band necrosis. Myoglobin diffusion paralleled the extent of necrosis. The case was useful in evaluating the effects of ischemia on a human subject because variations due to personality and postmortem changes were not involved. Actomyosin ATPase activity was not different among the various infarct and non-infarct regions examined except in one infarct region where it was higher.
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PMID:Sudden death case of single coronary artery with special reference to the effect of ischemia on actomyosin. 215 Apr 22

The relationship between the progression of sarcolemmal damage and the appearance of amorphous matrix densities (AMDs) within myocardial mitochondria in the early phase of ischemia was studied in coronary-ligated rats by means of electron microscopy. The animals were divided into six groups according to the duration of ischemia (from 10 to 120 min). The severity of sarcolemmal damage was graded into four classes according to the ultrastructural ischemic changes, as follows: grade 0, normal cells; grade 1, slight ischemic changes in cellular organelles but intact sarcolemma; grade 2, formation of subsarcolemmal blebs, but overall sarcolemmal integrity; and grade 3, sarcolemmal disruption. In the experiment, grade 1 cells decreased and those of grade 3 increased with a longer period of ischemia. The appearance of grade 3 cells was distinct at 30 min of ischemia. This cellular damage proceeded from the subendocardial layer to the subepicardial layer indicating the "wavefront phenomenon." The number of AMDs within the mitochondria increased as the sarcolemmal damage became more severe. It was noteworthy that AMDs could be found in cells with an intact sarcolemma after subjection to 10 min of ischemia. Myoglobin staining of the myocardium obtained after 10 min of ischemia followed by 6 hr of reperfusion revealed no loss of myoglobin, indicating no irreversible cell damage. This finding suggests that the formation of AMDs may occur prior to the disruption of the sarcolemma or irreversible cell damage.
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PMID:Relationship between sarcolemmal damage and appearance of amorphous matrix densities in mitochondria following occlusion of coronary artery in rats. 259 63

The relationships among isometric tension development, the oxidation-reduction states of pyridine nucleotides and cytochrome c, and the oxygenation state of myoglobin have been assessed using the arterially perfused rabbit interventricular septum under different conditions of contraction rate, perfusate [Ca2+] and pH, catecholamine stress, and hypoxia. Hypoxia was produced either by decreasing oxygen availability with maintained flow (high-flow hypoxia) or by decreasing the flow rate (ischemia). Under normoxic conditions, increased work caused a fall of the cytosolic adenine nucleotide phosphorylation potential, delta G(ATP)c, an oxidation of the pyridine nucleotides, and a reduction of cytochrome c; the opposite occurred with decreased work. Thus, the redox potential span from NADH to cytochrome c, delta Eh, varied with the energy demand such that delta Eh and delta G(ATP)c changed in the same direction. Under hypoxic conditions, all respiratory components became more reduced, and myoglobin was partially deoxygenated. The percentage change of developed tension under hypoxic conditions was approximately proportional to the percentage change of oxidized cytochrome c. When high-flow hypoxia and ischemia were compared at the same rates of oxygen delivery, the developed tension at any level of cytochrome c reduction was always lower with ischemia than with high-flow hypoxia. This difference was attributed to the low intracellular pH of ischemic tissue. Myoglobin deoxygenation was linearly related to cytochrome c reduction under all conditions of hypoxia, indicating steep oxygen gradients. The results support the concept of heterogeneous oxygenation of the tissue with mixed populations of aerobic and anaerobic mitochondria in the hypoxic state. In the full aerobic state, the control of mitochondrial respiration in situ appears similar to that of isolated mitochondria.
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PMID:Mitochondrial function in normal and hypoxic states of the myocardium. 630 29

Recent research has contributed to the understanding of nontraumatic rhabdomyolysis. In cases associated with coma, the pathophysiology is secondary to local pressure necrosis caused by compression from the patient's own body. The local pressure results in an edema-ischemia cycle concluding with compartmental tamponade and muscle breakdown. Myoglobin released by the damaged muscle indirectly induces the acute renal failure via its breakdown product, ferrihemate, which poisons renal tubular cells. Uric acid nephropathy may also play a role. Radionuclide scanning has assumed a significant role as a diagnostic tool to determine the extent of soft tissue injury. Early volume expansion and administration of sodium bicarbonate and mannitol are recommended as prophylaxis against renal failure. Fasciotomy appears to have a role both in the prevention of limb damage and in the diminution of the systemic toxic effects produced by muscle breakdown.
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PMID:Rhabdomyolysis secondary to drug overdose and prolonged coma. 740 37

Myoglobin and myosin light chain 1 (MLC1) are intracellular human cardiac marker proteins which are released as a consequence of ischemia. Human cardiomyocytes were isolated from fresh biopsies and also maintained for several passages in cell culture. The cardiomyocytes were fixed in 100% methanol at -20 degrees C, and labeled. The immunolocalization of intracellular antigen by fluorescence conjugated imaging was compared with scanning electron microscopy (SEM) backscatter electron (BSE) imaging of gold conjugated antibody. Ultra-violet light microscopy showed the intracellular distribution of both proteins to be mainly in the nuclear envelope, the cytoplasm immediately surrounding the nucleus and along portions of the cell membrane. To confirm this observed distribution of myoglobin and MLC1, labeling was repeated with antimyoglobin and anti-MLC1 monoclonal antibodies conjugated to colloidal gold particles. The advantage of colloidal gold labeling is that the intracellular antigen-antibody complexes may be more precisely located because of the significant improvement in resolution provided by BSE imaging in the SEM. BSE imaging confirmed the presence and subsarcolemma localization of myoglobin in cardiomyocytes directly isolated from fresh biopsies. The distribution of colloidal gold-conjugated antibodies did not coincide with the intracellular distribution of the two proteins in the cardiomyocytes grown in cell culture as indicated by immunofluorescence. A relatively random, intracellular gold particle distribution was confirmed by x-ray microanalysis. BSE imaging resulted in consistent auto-backscatter labeling patterns very similar to the labeling patterns obtained with immunofluorescent labeling. X-ray microanalysis confirmed that these auto-backscatter labeling patterns were formed by concentrations of intracellular phosphate. Sodium dodecyl sulfate-poly-acrylamide gel electrophoresis (SDS-PAGE) and subsequent Western blotting indicated that myoglobin and MLC1 were no longer present in detectable quantities in these cells after several passages. Polymerase chain reaction (PCR) amplification of mRNA for human myoglobin and cardiac MLC1 confirmed the absence of their transcripts. Electrophoretic analysis of proteins in cardiomyocytes grown in cell culture confirmed an increasing presence of alkaline phosphatase. Staining of this enzyme with 5-bromo-4-chloro-3-indolyl phosphate and nitroblue tetrazolium showed that alkaline phosphatase was distributed in the same intracellular pattern as the fluorescence conjugated anti-body and the phosphatase auto-backscatter. These results indicate that high-resolution backscatter SEM imaging may be used as necessary control to confirm fluorescence light microscope intracellular labeling of antigens.
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PMID:Advantages of backscatter electron imaging scanning electron microscopy for intracellular localization of cardiac analytes by gold conjugated antibody. 865 28

To evaluate the effect of reperfusion with hypertonic-hyperosmotic solution, cardiectomy was performed in 25 New Zealand white rabbits. Seven isolated hearts were submitted to 30 min of global ischemia and reperfused with oxygenated buffer for 60 min. Myoglobin and isoenzyme MB of creatine kinase concentrations were each measured in the effluent 15 min, and values were correlated (r = 0.5011, p = 0.015). After this procedure, 18 isolated hearts were randomized in two groups. Hearts of group I were reperfused with hypertonic-hyperosmotic solution (NaCl 7.5% dextran 60,000 MW) diluted in oxygenated buffer, and group II with oxygenated buffer. Myoglobin and coronary flow were measured in both groups, group I showed lower levels of myoglobin (p = 0.0069) and higher coronary flow (p = 0.028) than group II. In conclusion, changes in myoglobin concentration in the heart effluent are more sensitive than changes in isoenzyme MB of creatine kinase; thus, evaluation of this parameter may be useful in the detection of ischemia reperfusion injury. Additionally, hypertonic-hyperosmotic solution improves the coronary flow and has a protective effect against ischemia-reperfusion injury.
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PMID:Hypertonic-hyperosmotic solution modifies myoglobin levels in early reperfusion after ischemic cardiac arrest. Experimental model. 920 13

The effect of ischemic preconditioning (IP; 3 min ischemia plus 3 min reperfusion) on the recovery of cardiac function after Ca2+ depletion was investigated. Isolated rat hearts were subjected to different cycles of IP episodes followed by Ca2+ free perfusion and repletion. Perfusion of control hearts with Ca2+ free medium for 5 min followed by repletion of Ca2+ for 30 min resulted in a marked decrease in the left ventricular (LV) developed pressure and an increase in LV end-diastolic pressure (Ca2+ paradox). The depressed function due to Ca2+ paradox recovered with three cycles of IP. Myoglobin release during Ca2+ repletion also decreased significantly by three cycles of IP. The beneficial effects of IP were also evident when the hearts were subjected to a mild form of Ca2+ paradox involving 3 min Ca2+ depletion. The protective effect rendered by IP disappeared when 10 microM of 8-(p-sulfophenyl)-theophylline, adenosine antagonist was perfused for 10 min before IP. These results suggest that IP exerts beneficial effects on Ca2+ paradox which may be mediated by adenosine.
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PMID:Beneficial effect of ischemic preconditioning on Ca2+ paradox in the rat heart. 971 97

Aims of the study: The evaluation of significant perioperative ischemic processes after coronary artery bypass grafting from postoperative ECG, creatine kinase (CK) and CK iso-enzyme MB remains unreliable and, hence, insufficient. Additional, early available biochemical markers could improve the diagnostics of ischemia. Methods: In 86 patients with multiple vessel disease, activity of serum CK and CK-MB as well as mass of CK-MB, myoglobin and troponin-T were analyzed before and after surgery. Twelve-lead electrocardiograms were evaluated before surgery, 3h postoperatively, and before discharge from hospital. Results: In patients with signs of perioperative ischemia in the 3-hour ECG, primary postoperative peak values of myoglobin and CK were distinctly higher than in patients without signs of ischemia, with median values of 1437 ng/ml vs. 986 ng/ml for myoglobin and of 632 U/l vs. 481 U/l (n.s.) for CK. Sensitivity and specificity of myoglobin were 64 % and 69 %, followed by CK with 61 % and 62 %, respectively. Conclusions: Myoglobin, indicating the risk of perioperative ischemia approximately 45 minutes after declamping of the aorta, is suggested as a candidate for early available routine monitoring.
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PMID:Biochemical markers of perioperative myocardial ischemia in patients with coronary artery bypass grafting. 1035 35

The source(s) of reactive partially reduced oxygen species associated with myocardial ischemia/reperfusion injury remain unclear and controversial. Myoglobin has not been viewed as a participant but is present in relatively high concentrations in heart muscle and, even under normal conditions, undergoes reactions that generate met (Fe3+) species and also superoxide, hydrogen peroxide, and other oxidants, albeit slowly. The degree to which the decrease in pH and the freeing of copper ions, as well as the variations in pO2 associated with ischemia and reperfusion increase the rates of such myoglobin reactions has been investigated. Solutions of extensively purified myoglobin from bovine heart in 50 mM sodium phosphate buffer were examined at 37 degrees C. Sufficiently marked rate increases were observed to indicate that reactions of myoglobin can indeed contribute substantially to the oxidant stress associated with ischemia/reperfusion injury in myocardial tissues. These findings provide additional targets for therapeutic interventions.
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PMID:Potential roles of myoglobin autoxidation in myocardial ischemia-reperfusion injury. 1040 2


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