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

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.
 ...
PMID:Advantages of backscatter electron imaging scanning electron microscopy for intracellular localization of cardiac analytes by gold conjugated antibody. 865 28

The effect of three cardioplegic protocols on perioperative myocardial injury was studied in 62 coronary artery bypass grafting (CABG) patients randomized into three groups with either antegrade or retrograde cold blood cardioplegia, or coronary sinus occlusion during antegrade supply. During the aortic cross-clamp time anterior and posterior septal temperatures were recorded, indicating the distribution of cardioplegic solution within the myocardium. Serum creatine kinase (CK), CK-isoenzyme MB and myoglobin as well as 12-lead electrocardiograms (ECG) were analyzed. Statistical analysis showed no effect of the cardioplegic protocol, whereas the patient's preoperative status, aortic cross-clamp time and intraoperative myocardial temperature had significant (P < 0.05) effects on immediate postoperative CK and CK-MB enzyme release. Creatine kinase-MB peak values were significantly increased in patients with major vessel disease and reduced left ventricular function (92 +/- 53 U/l versus 67 +/- 25 U/l). Both CK and CK-MB values were significantly higher in patients with aortic cross-clamp times of more than 1 h than in patients with shorter clamping times (661 +/- 188 and 78 +/- 40 U/l versus 500 +/- 200 and 57 +/- 24 U/l). Patients with 22 +/- 3 degrees C myocardial temperature before terminal cardioplegia had significantly elevated CK as compared to patients with temperatures of 15 +/- 2 degrees C (665 +/- 185 U/l versus 510 +/- 211 U/l). However, enzyme peak values had only poor predictive power for postoperative ECG changes, suggesting that enzyme peaks were not necessarily a sign of perioperative ischemia. Patients with major vessel disease and reduced myocardial function, with aortic cross-clamp time of more than 1 h and/or inadequate intraoperative myocardial cooling may be highly susceptible to global ischemia and operative procedures, and therefore show elevated peak enzyme levels shortly after surgery. In contrast, elevated myoglobin peaks within 1 h after aortic declamping were significantly correlated to perioperative signs of transient ischemia (P < 0.02).
 ...
PMID:Perioperative myocardial injury with different modes of antegrade and retrograde cardioplegic delivery. 866 19

Although rare, exertional collapse and sudden death are the most serious potential complications of sickle cell trait. Studies suggest that this condition may occur in susceptible persons when poor physical conditioning, dehydration, heat stress or hypoxic states precipitate sickling of the abnormal erythrocytes. Sickling leads to endothelial damage, which can cause vasoconstriction, disseminated intravascular coagulation and local tissue damage. Cardiac effects include acute ischemia and arrhythmias. Muscle damage results in acute compartment syndromes and release of myoglobin into the circulation. Acute renal failure is possible. Diagnosis is based on a high index of suspicion, and characteristic presentation and laboratory findings, including myoglobinuria, hyperkalemia, hypocalcemia, hyperphosphatemia and elevated creatine kinase levels. The differential diagnosis includes pulmonary embolism, acute cardiac events, anaphylaxis and heat stroke. Management is based on stabilization, rehydration, and the treatment and prevention of complications.
 ...
PMID:Exertional collapse and sudden death associated with sickle cell trait. 904 99

Perfused rat heart experiments focused on determining the critical O2 level in postischemic myocardium. After a 20-min global ischemia, reperfusion began with O2-saturated saline buffer reflowing at different rates (0.5-12 ml/min). The 1H nuclear magnetic resonance (NMR) signal of the Val E11 myoglobin (Mb) gave an index of the intracellular oxygenation, whereas the 31P-NMR spectra reflected the high-energy phosphate and pH status. At the same time, physiological monitors recorded both contractile function and O2 consumption. Biochemical analysis determined the lactate concentration. Within 6-12 min of reperfusion, the O2 reached a new steady state, which depended directly on the flow rate. Below 12 ml/min reflow, the postischemic O2 level was consistently lower than the corresponding control values. Phosphocreatine, P(i), pH, myocardial O2 consumption, and lactate formation rate exhibited a similar linear relationship with MbO2 saturation in both the control and postischemic myocardium. It appears that neither the cellular energy production nor the steep intracellular O2 gradient has changed substantially in the postischemic myocardium.
 ...
PMID:Cellular response to reperfused oxygen in the postischemic myocardium. 877 Jan 12

It is known that treatment of myoglobin with H2O2 leads to covalent alteration of the heme prosthetic group with concomitant formation of a protein bound heme adduct and transforms myoglobin from an oxygen storage protein to an oxidase. In the current study it was shown, with the use of 14C-labeled heme reconstituted into apomyoglobin, that up to 88% of the oxidatively altered heme can be accounted for by the protein bound product. Furthermore, a partially purified preparation of the protein bound heme adduct was introduced into human fibroblasts using the method of osmotic lysis of pinosomes and found to cause cell death (40%) within 1 h, as evidenced by trypan blue exclusion. Native myoglobin introduced into cells in the same manner or extracellular treatment by the protein bound heme adduct had no effect on cell viability. The extent of cell death could be decreased (50%) by N-acetyl-L-cysteine, indicating a potential role for reactive oxygen intermediates in this process. These results show that the covalently altered myoglobin can elicit cellular damage and suggests that similar processes may occur in vivo in pathologic conditions such as that involving cardiac ischemia and reperfusion injury, where covalently altered myoglobin may form.
 ...
PMID:Covalent crosslinking of the heme prosthetic group to myoglobin by H2O2: toxicological implications. 879 Oct 91

It has been shown by a number of authors that early myocardial infarction constitutes a dynamic process of cyclic oscillation between coronary occlusion and spontaneous coronary reopening. Infarct-markers, such as ST-segment elevation, serum-creatine kinase isoenzyme MB, the atrionatriuretic peptide (ANP) and serum-myoglobin (Mb) exhibit cyclic behaviour pattern during early AMI and thus reflect episodes of intermittent, spontaneous reperfusion. The latter have recently been verified by angiography. The mechanism underlying the phenomena seen in early myocardial infarction is likely to be based on a constant vasoconstrictive stimulus, deriving from aggregating platelets. The vasoconstriction subsequent to platelet aggregation produces an initial episode of myocardial ischemia. This episode is followed by a hypoxia of the artery wall. Reactive coronary dilation secondary to ischemia is than promoted by the release of vasoactive by-products of anaerobic glycolysis as well as changes in the open propability of certain transmembrane ion channels. Thereafter, the initial coronary occlusion is interrupted by transient vasodilation. A wave of reperfusion follows and leads to reoxygenation and wash-out of ischemia-induced vasodilative components as well as biochemical markers. The vasoconstrictive forces then take over again. This results in repeated waves of reperfusion. A number of arguments in favour of this concepts are discussed in this paper.
 ...
PMID:Cyclic phenomena in early myocardial infarction. 883 24

The purpose of this study was to determine whether the initial rate of hemoglobin and myoglobin deoxygenation during immediate postexercise ischemia, a reflection of muscle O2 consumption (VO2mus), can be a quantitative measure of muscle oxidative metabolism. The finger flexor muscles of five healthy men (aged 25-31 yr) were monitored by 31P-magnetic resonance spectroscopy for changes in phosphocreatine (PCr), Pi, and pH. Tests were conducted during 15 min of cuff ischemia and during 5 min of submaximal isotonic grip exercise at 10, 20, 30, and 40% of maximal voluntary contraction, one contraction every 4 s. The VO2mus changes were also monitored by near-infrared spectroscopy with continuous wave. The VO2mus during exercise was expressed relative to the resting value. The resting metabolic rate, calculated from the PCr breakdown rate after complete O2 depletion, was 0.0010 (SD) mM ATP/s. During submaximal exercise (pH > 6.9), the VO2mus increased with a rise in intensity (0.036 +/- 0.011, 0.054 +/- 0.016, 0.062 +/- 0.012, and 0.067 +/- 0.020 mM ATP/s during 10, 20, 30, and 40% maximal voluntary contraction, respectively) and showed significant correlation with changes in both calculated ADP and PCr values (r2 = 0.98 and r2 = 0.99, respectively). In conclusion, because of the significant correlation with regulatory metabolites (ADP and PCr) of oxidative phosphorylation, O2 decline rate in immediate postexercise ischemia determined by near-infrared spectroscopy with continuous wave can be utilized for the quantitative evaluation of localized muscle oxidative metabolism.
 ...
PMID:Noninvasive measures of oxidative metabolism on working human muscles by near-infrared spectroscopy. 888 81

In the normal beating heart, oxygen pressure (PO2) gradients between capillary blood and intracellular space are so large that cytosolic PO2 may decline to around PO2 at half saturation of myoglobin (2-5 Torr). Hence, a decrease in capillary blood PO2 of a few Torr would easily deplete oxygen in mitochondria if PO2 gradients are unchanged. The aim of the present study was to demonstrate, in a single isolated cardiac myocyte of the rat, a mechanism that reduces PO2 gradients in hypoxia so that oxygenation of the intracellular space would be sustained. Using a newly developed microspectrophotometric device, we were able to follow changes in cytosolic PO2 of an individual ventricular myocyte in an hypoxic medium. For extracellular PO2 of 4.4 Torr, we found an elevation (2.1 Torr) of the cytosolic PO2 when oxygen consumption of the cell was abolished by 2 mM NaCN, thus demonstrating PO2 gradients from extracellular medium to cytosolic space in a single individual cardiomyocyte. The magnitude of these PO2 gradients was reduced as extracellular PO2 was further lowered, and they were no longer detectable for extracellular PO2 of 0.6 Torr. To further elucidate physiological effects of the PO2-dependent changes in PO2 gradients demonstrated above, we conducted a simulation of ischemia in a single cardiac myocyte. The stop-flow procedure (simulated ischemia) quickly decreased cytosolic PO2 from 7.3 to 1.8 Torr in 5 min, while the rate of fall of PO2 considerably decreased when the cytosolic PO2 decreased to < 2 Torr. Consequently, even 30 min after the onset of the stop flow, cytosolic PO2 was significantly higher than that of the anoxic perfusion. These results together suggest that in severe hypoxia oxygenation of the intracellular space might be partially maintained by relative elevation of cytosolic PO2, resulting from progressive decrease in PO2 gradients from extracellular space to cytosol.
 ...
PMID:Regulation of oxygen diffusion in hypoxic isolated cardiac myocytes. 894 85

Carbon monoxide (CO) poisoning still represents a frequent and severe casualty in France. Aside from the well-known effect of CO on hemoglobin, the role of CO binding to other hemoproteins like myoglobin and cytochrome a3 has been more recently recognized. Moreover, in addition to these hypoxic injuries, the reoxygenation phase may itself induce toxic effects by a mechanism close to the ischemia-reperfusion phenomenon. Clinical manifestations include neurologic disturbances, cardiac arrhythmia, respiratory and circulatory failures which usually disappear with removal from toxic atmosphere and administration of oxygen. However, long term neurologic manifestations may occur and lead to important functional impairment and disability. Hyperbaric oxygen is actually the treatment of choice to avoid the occurrence of delayed sequelae. HBO is advocated in every patient who remains comatose on hospital admission, who has lost consciousness during toxic exposure or with persisting neurologic abnormalities. CO poisoned pregnant women should also undergo HBO.
 ...
PMID:[Carbon monoxide poisoning]. 895 70

Carbon monoxide (CO) poisoning still represents a frequent and severe casualty in France. Aside the well-known effect of CO on hemoglobin, the role of CO binding to other hemoproteins like myoglobin and cytochrome a3 have been more recently recognized. Moreover, in addition to these hypoxic injuries, the reoxygenation phase may itself induce toxic effects by a mechanism close to the ischemia-reperfusion phenomenon. Clinical manifestations include neurologic disturbances, cardiac arrythmia, respiratory and circulatory failures which usually disappear with removal from toxic atmosphere and administration of oxygen. However, long term neurologic manifestations may occur and lead to important functional impairment and disability. Hyperbaric oxygen in actually the treatment of choice to avoid the occurrence of delayed sequelae. HBO is advocated in every patient who remains comatose on hospital admission, who had lost consciousness during toxic exposure or with persisting neurologic abnormalities. CO poisoned pregnant women should also undergo HBO. Well designed prevention programs are urgently needed in our country to decrease the incidence and the consequences of CO poisoning.
 ...
PMID:[Carbon monoxide poisoning: current aspects]. 896 14


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>