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)

In the conclusion of this series of reports, the application of 31P/2H NMR to investigate the pathophysiology of sepsis in rat hindlimb muscle is demonstrated. Sepsis decreased muscle [PCr] by 18%, 18 +/- 4 SD vs 22 +/- 4 SD mmol/kg tissue wet wt (P = 0.01) in control rats but [ATP] was unchanged, 6 mmol/kg tissue wet wt (P = 0.2). The derived free cytosolic [ADP] in the two groups was similar, [ADP]septic = 0.023 +/- 0.004 SD and [ADP]control = 0.021 +/- 0.003 SD mmol/kg tissue wet wt, and not statistically different (P = 0.14). Likewise [Pi] in the septic and control groups was not statistically different, [Pi]septic = 1.1 +/- 0.5 SD and [Pi]control = 1.2 +/- 0.4 SD mmol/kg tissue wet wt (P = 0.2). Septic rats presented the symptom of respiratory alkalosis evidenced by elevated blood pH. Sepsis decreased muscle blood flow by 33%, P = 0.003, but examination of individual subjects did not demonstrate a correlation with the reduction in [PCr]. Thus, a metabolic energy deficit caused by cellular ischemia/hypoxia is not a likely cause of cellular abnormality in rat hindlimb muscle during sepsis.
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PMID:Concurrent quantification of tissue metabolism and blood flow via 2H/31P NMR in vivo. III. Alterations of muscle blood flow and metabolism during sepsis. 159 58

Experiments were designed to determine whether endothelial cell injury contributes to increased coronary vascular tone after global cardiac ischemia and reperfusion. Canine hearts were exposed to global ischemia for 45 minutes and were reperfused for 60 minutes. Rings (5 to 6 mm long) of the left anterior descending coronary artery from reperfused hearts and from normal (control) hearts were suspended for isometric force measurement in organ chambers containing physiologic salt solution (37 degrees C, and 95% oxygen and 5% carbon dioxide). After contraction with prostaglandin F2 alpha, reperfused coronary arteries had significant impairment of endothelium-dependent relaxations to aggregating platelets (52% +/- 12% relaxation versus 102% +/- 11% for control segments; p less than 0.05). Reperfused arterial rings also exhibited impaired endothelium-dependent relaxations to the receptor-dependent agonist acetylcholine and the platelet-derived compounds adenosine diphosphate and serotonin. Importantly, endothelium-dependent relaxations to the non-receptor-dependent agonist A23187 were normal after ischemia and reperfusion. Quiescent (noncontracted) reperfused arterial rings lost the ability to counteract the constrictive effect of aggregating platelets on the coronary vascular smooth muscle (24% +/- 7% contraction versus 5% +/- 2% relaxation for control segments; p less than 0.05). Endothelium-independent contractions to potassium chloride and prostaglandin F2 alpha were similar in reperfused and normal arteries. Also, endothelium-independent relaxations to nitric oxide and isoproterenol were comparable in reperfused arteries and normal vessels. Thus global cardiac ischemia and reperfusion impair the normal endothelium-dependent relaxations to aggregating platelets and other receptor-dependent vasoactive drugs. This impairment of platelet-mediated coronary vasodilation may explain increased coronary vascular tone after cardiopulmonary bypass and could be an important pathophysiologic mechanism of postoperative coronary vasospasm.
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PMID:Global myocardial ischemia and reperfusion impair endothelium-dependent relaxations to aggregating platelets in the canine coronary artery. A possible cause of vasospasm after cardiopulmonary bypass. 159 79

Using NADH fluorometry to monitor myocardial metabolism, the mechanism of reperfusion injury was investigated after the delivery of an experimental reperfusate. Using an isolated working heart preparation, rat hearts underwent 15 min of global ischemia at 37 degrees C. Following the ischemic insult, an oxygenated enriched reperfusion solution was given for 5 min. The hearts were then returned to a working state and aortic flow recorded to evaluate recovery. NADH levels were monitored throughout the experiment with a fluorometer and glycogen, AMP, ADP, and ATP were measured biochemically pre- and postischemia, after reperfusion and after recovery. In this study, reperfusion injury was best abated by an enriched reperfusate. Our results indicate the mechanism for this amelioration is not high-energy phosphate replenishment. Rather, as indicated by NADH fluorescence, the hearts attain an intermediate level of metabolism that permits glycogen to be restored and functional recovery to be improved.
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PMID:Monitoring myocardial reperfusion injury with NADH fluorometry. 161 62

Preimplantation preparation of cardiac valves includes three major steps: (1) harvesting with accompanying ischemia (warm time from cessation of donor heart beat), (2) antibiotic disinfection, and (3) controlled-rate cryopreservation. To define the interdependent injury effects of these manipulations on leaflet matrix cells and specifically the potential for prolonged harvest-related ischemia to predispose greater injury by the subsequent steps, 96 semilunar valves were harvested from pigs in a manner analogous to human heart valve retrievals and randomly allocated to study groups as follows: 48 control valves were exposed to increasing harvested-related ischemic times, (2, 6, 12, 24 hr) and immersed in liquid nitrogen to arrest metabolic activity (i.e., prior to cryopreservation) and conclude the ischemia; another 48 were similarly harvested, subjected to identical ischemic times, then disinfected in 4 degrees C RPMI medium with standard antibiotics for 24 hr and dimethylsulfoxide cryopreserved at -1 degrees C/min to -170 degrees C (i.e., formal cryopreservation protocol). At thawing, each valve was extracted in 12% trichloroacetic acid and assayed by high performance liquid chromatography for components of the adenine nucleotide pool including ATP, lower energy nucleotides (total adenine nucleotides, [TAN] = [ATP] + [ADP] + [AMP]), adenosine, and the diffusible purines. Results are reported as nanomoles metabolite/milligram of leaflet cell protein (Lowry) and reflect a maintenance of total high energy phosphates in the control groups (5.41 +/- 0.29 nmole TAN at 2 hr; 8.34 +/- 0.67 nmole TAN at 24 hr), which fell significantly in all cryopreserved groups (1.27 +/- 0.33 nmole TAN at 2 hr; 0.34 +/- 0.22 nmole TAN at 24 hr).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High energy phosphate depletion in leaflet matrix cells during processing of cryopreserved cardiac valves. 161 17

The aim of this study was to determine the significance of the "coronary factor" in patients with essential hypertension (EH). Electrocardiogram Holter monitoring was performed in 61 patients with EH stage II (according to the World Health Organization criteria). Silent, ie, painless ST-segment depression, was found in 34 patients on whom echocardiography, a treadmill test, and transesophageal pacing were performed. In 21 patients with EH and silent ischemia, the examination included 201Tl stress scintigraphy, coronary angiography, and a platelet aggregation test. In 15 patients, catecholamines and beta-endorphins were obtained in blood samples during silent ischemia. 201Tl scintigraphy showed transient defects of perfusion without clearance abnormalities (group I) and with clearance abnormalities (group II). The patients in group I had more severe left ventricular hypertrophy (LVH) and a significantly higher platelet aggregation response to 0.5 mumol/L adenosine diphosphate; one patient in this group had coronary atherosclerosis. LVH and the platelet aggregation response was less pronounced in the patients in group II, but atherosclerotic lesions of a coronary artery were observed in four patients. In both groups, norepinephrine and beta-endorphin levels were increased during silent episodes of ischemia. The results suggest that there are different pathogenetic mechanisms of coronary insufficiency in patients with EH, a hypertensive heart, and silent ischemia.
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PMID:Silent myocardial ischemia in patients with essential hypertension. 163 37

We administered fructose-1,6-bisphosphate (FDP), 1 mM, to isolated and perfused rabbit hearts submitted, after 90 minutes of equilibration, to an ischemic period (60 minutes at a coronary flow of 0.17 ml/min/g), followed by a period of reperfusion (30 minutes at a coronary flow of 3.6 ml/min/g). FDP was delivered at different times following the experimental protocol: 60 minutes before ischemia and for the entire experiment; 60 minutes before and during ischemia, but not at reperfusion; at the onset of ischemia and during reperfusion; and only during reperfusion. The FDP cardioprotective effect was evaluated in terms of recovery of left ventricular pressure developed during reperfusion, creatine phosphokinase (CPK) and noradrenaline release, mitochondrial function (expressed as yield, RCI, QO2, ADP/O), ATP and creatine phosphate (CP) tissue contents, calcium homeostasis, and by measuring oxidative stress in terms of reduced and oxidized glutathione release and tissue contents. Our data show that the cytoprotective action of FDP is closely related to the time of administration. Optimal myocardial preservation was achieved when it was present prior to ischemia and during reperfusion. When given at the time of ischemia or only on reperfusion, FDP does not exert cardioprotection. The data suggest that the FDP cardioprotective effect is related to improvement of energy metabolism.
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PMID:Role of timing of administration in the cardioprotective effect of fructose-1,6-bisphosphate. 163 29

Isolated canine hearts were preserved at 4 degrees C with multi-dose cardioplegic solution every hour for 6 hours. Reperfusion was observed for 2 hours under cross-circulation without cardiotonic drugs. The aprotinin group (n = 8), which received cardioplegic solution with added aprotinin (150 KIU/mL), was compared with the control group (n = 6). The increase in tissue adenosine triphosphate and total adenine nucleotide content during reperfusion was significant in the aprotinin group; there was no change in the control group, and the levels at the end of reperfusion tended to be higher in the aprotinin group than in the control group. Tissue adenosine diphosphate levels remained unchanged in both groups. Tissue adenosine monophosphate levels declined during reperfusion in both groups and were slightly lower in the control group. Tissue levels of cyclic adenosine monophosphate remained unchanged in the aprotinin group whereas they increased during ischemia and declined significantly during reperfusion in the control group. Tissue levels of cyclic guanosine monophosphate declined during reperfusion in both groups without difference. Creatine phosphate levels recovered in both groups without difference. Serum cyclic guanosine monophosphate concentration tended to be lower in the aprotinin group than in the control group. Serum creatine kinase-MB level increased slightly during reperfusion in both groups without difference. N-acetyl-beta-D-glucosaminidase levels were significantly suppressed during reperfusion in the aprotinin group as compared with the control group. These results suggest that aprotinin is effective in preserving adenine nucleotide and adenosine triphosphate levels and in stabilizing tissue cyclic adenosine monophosphate levels in prolonged hypothermic cardioplegic preservation followed by reperfusion.
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PMID:Effect of aprotinin to improve myocardial viability in myocardial preservation followed by reperfusion. 171 31

The effect of normothermic ischemia and ischemia/reperfusion on the function of cardiac sarcoplasmic reticulum (CSR) was investigated using a modified Langendorff perfusion of isolated rat hearts. The function of the CSR was assessed by the oxalate-supported Ca2+ uptake rate of ventricular homogenates. The contribution of the ryanodine-sensitive portion of the CSR was determined by using 20 microM ruthenium red or 625 microM ryanodine to close the CSR Ca2+ release channel. The Ca2+ uptake rate of the CSR decreased progressively with increasing duration of ischemia, but this depression was much less when uptake was assayed in the presence of ryanodine. The depression in CSR Ca2+ uptake preceded ischemic contracture. Ryanodine and ruthenium red stimulated uptake almost equally in control hearts, but ruthenium red was much less effective than ryanodine after ischemia. This difference could not be overcome by increasing the ruthenium red concentration. These results confirm the suggestion that the Ca2+ release channel is inappropriately opened after ischemia. The CSR uptake rates were almost completely restored at 15 minutes of reperfusion after 5 and 10 minutes of ischemia but were only partially restored after 15 minutes of ischemia. At reperfusion, mechanical function (end-diastolic pressure and peak systolic developed pressure) was markedly depressed after only 15 minutes of ischemia. The degree of "stunning" correlated well with the depression of CSR function in individual hearts. The decreased Ca2+ uptake of the CSR was not due to a buildup of ADP in the homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reversibility of the effects of normothermic global ischemia on the ryanodine-sensitive and ryanodine-insensitive calcium uptake of cardiac sarcoplasmic reticulum. 172 84

This study assessed gentamicin's effects on ischemia/reperfusion renal injury to better understand when and how it worsens postischemic acute renal failure. Rats were subjected to 25 minutes of renal pedicle occlusion with and without preischemic (15-minute) or postischemic (15-minute or 8-hour) gentamicin treatment (100 mg/kg, by itself a subtoxic dose). Gentamicin's impact on hypoxia/reoxygenation injury to isolated rat proximal tubular segments was also assessed. Preischemic and postischemic gentamicin worsened the severity of acute renal failure to the same degree, suggesting that pretreatment induces its effect in the reperfusion period. Gentamicin paradoxically lessened hypoxic damage to proximal tubular segments (assessed by lactate dehydrogenase release), again implying no adverse impact on oxygen deprivation-induced tubular injury. From 0-4 hours of reperfusion, gentamicin approximately halved ATP/ADP ratios (due to increased ADP), indicating a drug-induced defect in cellular energetics. This abnormality temporally correlated with evolving morphological damage. Although antioxidants (deferoxamine and sodium benzoate) have been reported to protect against pure aminoglycoside nephrotoxicity, they did not mitigate gentamicin's adverse impact on postischemic acute renal failure. Gentamicin did not influence ischemia/immediate reperfusion deacylation/reacylation (assessed by renal free fatty acid content) despite its known antiphospholipase activity. Although in the normal kidney gentamicin preferentially accumulated in cortex, in the postischemic kidney, both cortex and outer medullary stripe developed striking (approximately threefold to fivefold) and comparable gentamicin increments. In conclusion, gentamicin appears to exacerbate postischemic acute renal failure by adversely influencing the reperfusion, not the ischemic injury, process. This may occur because increased gentamicin accumulation negatively impacts on reperfusion cellular energetics.
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PMID:Gentamicin effects on renal ischemia/reperfusion injury. 172 86

Myocardial ATP, ADP, and AMP were measured from cardiac biopsy in 11 dogs after intracoronary injection of 6 mL of sodium-meglumine diatrizoate (SMD), iohexol (IOH), or 0.9% sodium chloride (NaCl), and in three of the dogs at baseline before any injection. The ATP at baseline and after SMD, IOH, and 0.9% NaCl were 5.39 +/- 0.41, 3.72 +/- 0.70, 5.52 +/- 0.82, and 5.44 +/- 1.40 mumol/g wet weight, respectively. There were significant differences between SMD and IOH (P less than .02), and between SMD and 0.9% NaCl (P less than .05). The energy charge of SMD was 0.82 +/- 0.08, which differed from 0.89 +/- 0.02 for NaCl or 0.9 +/- 0.05 for baseline (P less than .05), but not from 0.85 +/- 0.04 for IOH. In conclusion, diatrizoate caused significant depletions in ATP stores in comparison with iohexol, but there was no significant difference with respect to energy charge. Nonionic contrast media would be preferable for coronary arteriography in patients whose high-energy stores might be depleted from severe ischemia.
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PMID:Effects of intracoronary administration of contrast media on myocardial high-energy phosphate. A comparison of sodium meglumine diatrizoate and iohexol. 173 78


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