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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concentrations of purine catabolites in the cerebral interstitial fluid during progression of and recovery from ischemia were studied using brain microdialysis and high-performance liquid chromatography. Sealed 0.5-mm hollow dialysis fibers were stereotactically implanted into either the cerebral cortex or hippocampus of ketamine anesthetized gerbils and perfused with artificial cerebrospinal fluid at 2 microliters/min. Cerebral ischemia was induced by occlusion of the bilateral common carotid arteries. The reflectance spectra of oxy- and deoxyhemoglobin at the brain surface were monitored over the scalp to assess ischemia and confirm recirculation. Ischemia caused a rapid, 4.8-fold increase in the extracellular concentration of adenosine. The progressive increase in the concentration of adenosine, inosine, and hypoxanthine soon after recirculation is particularly interesting. The subsequent decrease in purine compound concentration was rapid for adenosine but more gradual for inosine and hypoxanthine. Calculated K values for adenosine deaminase and purine nucleoside phosphorylase were 0.045/min and 0.016/min, respectively. However, no xanthine, uric acid, or purine nucleotides were found in the perfusate. These observations indicated the presence of purine catabolites in the cerebral interstitial space as well as consecutive degradation and recycling involving the interconversion of purine compounds by biochemical metabolic pathways.
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PMID:Purine catabolites in cerebral interstitial fluid during progression of and recovery from ischemia. 171 45

The effect of ischemia and reperfusion on purine nucleoside phosphorylase was studied in an isolated perfused rat liver model. This enzyme is localized primarily in the cytoplasm of the endothelial and Kupffer cells; some activity is associated with the parenchymal cells. Levels of this enzyme accurately predicted the extent of ischemia and reperfusion damage to the microvascular endothelial cell of the liver. Livers from Lewis rats were subjected to 30, 45 and 60 min of warm (37 degrees C) no flow ischemia that was followed by a standard reperfusion period lasting 45 min. Purine nucleoside phosphorylase was measured at the end of the no flow ischemia and reperfusion periods as was superoxide generation (O2-). Bile production was monitored throughout the no flow ischemia and reperfusion periods. Control perfusions were carried out for 120 min. A significant rise in purine nucleoside phosphorylase levels as compared with controls was observed at the end of ischemia in all the three groups. The highest level, 203.5 +/- 29.2 mU/ml, was observed after 60 min of ischemia. After the reperfusion period, levels of purine nucleoside phosphorylase decreased in the 30- and 45-min groups 58.17 +/- 9.66 mU/ml and 67.5 +/- 17.1 mU/ml, respectively. These levels were equal to control perfusions. In contrast, after 60 min of ischemia, levels of purine nucleoside phosphorylase decreased early in the reperfusion period and then rose to 127.8 +/- 14.8 mU/ml by the end of reperfusion (p less than 0.0001). Superoxide generation at the beginning of reperfusion was higher than in controls with similar values observed at the end of 30, 45 and 60 min of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Purine nucleoside phosphorylase: a new marker for free oxygen radical injury to the endothelial cell. 215 67

This study aimed at analyzing the involvement of platelet activating factor (PAF) in ischemia/reperfusion injury (I/R) of the liver. Male Wistar rats under pentobarbital anesthesia were subjected to 60 min of normothermic ischemia of the left and median liver lobes, followed by 30 min of reperfusion in vivo. Blood pressure and body temperature were controlled throughout the experiment. Preischemic injection of a specific PAF antagonist (BN52021, 5 mg/kg body mass) resulted in significant reduction of postischemic enzyme loss into the serum from the vascular endothelium (purine nucleoside phosphorylase: 56.9 +/- 11.4 vs 86.6 +/- 20.4 U/l**) and the hepatic parenchyme (alanine aminotransferase: 176 +/- 60 vs 519 +/- 180 U/l***), accompanied by a significant increase of hepatic bile production (1.28 +/- .32 vs 0.80 +/- 0.16 microliter/g/min*) and tissue levels of ATP (6.12 +/- 1.73 vs 4.21 +/- 1.30 mumol/g*). Laser Doppler flowmetry revealed a significant improvement by BN52021 of left lobular erythrocyte flux recovery from 27 +/- 25 to 78 +/- 19% of respective preischemic control values. The data give evidence for an implication of PAF in I/R damage to the vascular endothelium and in impaired parenchymal function of the liver, probably due to altered microvascular reperfusion. Treatment with PAF antagonists should improve results after liver surgery under ischemic conditions. (*;**;***: P < 0.05; 0.01; 0.001).
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PMID:Involvement of platelet activating factor in microcirculatory disturbances after global hepatic ischemia. 774 67

Rat liver was kept at 4 degrees C or 37 degrees C in MEM, and reperfused through a closed circulation from the hepatic vein to the portal vein at 37 degrees C with the same solution. Although purine nucleoside phosphorylase and ALT activities were increased in the perfusate, depending on the duration of ischemia at both 4 degrees C and 37 degrees C, the ratio of the latter to the former was significantly higher after 37 degrees C-ischemia than after 4 degrees C-ischemia. The stimulation stage of Kupffer cells evaluated in situ by formazan deposition after liver perfusion with nitro blue tetrazolium and phorbol myristate acetate was elevated after 4 degrees C-ischemia longer than 1 h, but not after 37 degrees C-ischemia. In contrast, the degree of oxidative stress in hepatocytes assessed by formazan deposition after liver perfusion with nitro blue tetrazolium alone was greater after 37 degrees C-ischemia than after 4 degrees C-ischemia. These results suggest that oxidative stress in hepatocytes and the stimulatory state of Kupffer cells after ischemia-reperfusion may differ between 4 degrees C-ischemia and 37 degrees C-ischemia, probably leading to different development of liver damage.
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PMID:Oxidative stress in hepatocytes and stimulatory state of Kupffer cells after reperfusion differ between warm and cold ischemia in rats. 799 81

S-Adenosylmethionine (SAMe) and N-acetylcysteine (NAC), two agents with known benefit for reducing hepatic injury, were used to treat ischemic injury in a rat liver perfusion model. We compared cold ischemic injury with sequential periods of cold and warm ischemia that equate to episodes during the storage and implantation of liver grafts. The additional period of 20 min warm ischemia after 24 hr cold ischemia profoundly impaired initial (15 min) mean blood flow (1.8 +/- 0.1 vs. 2.7 +/- 0.4 ml/min/g liver for cold ischemia, P < 0.001) and bile flow (2.31 +/- 0.74 vs. 10.6 +/- 3.96 mg/hr/g liver for cold ischemia, P < 0.001) and increased the oxygen extraction ratio (OER) (0.53 +/- 0.03 vs. 0.29 +/- 0.08 for cold ischemia, P < 0.01) and acid release from glycolysis (0.18 +/- 0.02 vs. 0.11 +/- 0.02 mmol/g liver for cold ischemia, P < 0.05). Impairment of blood flow, bile flow, and OER was sustained throughout the 3-hr perfusion. In the same model, SAMe restored hepatic blood flow to control values when administered to the donor, included in the UW, and added as a bolus to the perfusate on reperfusion. SAMe also improved OER (P < 0.001 vs. sequential cold and warm ischemia) and initial bile flow (9.63 +/- 2.01 mg/hr/g liver, P < 0.01), returning values to control levels by 3 hr. SAMe reduced the initial release of glucose upon reperfusion (P < 0.01) and improved subsequent glucose uptake, but corresponding benefits on enzyme release from damaged hepatocytes (AST) or endothelial cells (purine nucleoside phosphorylase) were not observed. Equimolar concentrations of NAC induced transitory improvements in blood and bile flow but these were not sustained beyond 30 min of reperfusion.
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PMID:Evidence that S-adenosylmethionine and N-acetylcysteine reduce injury from sequential cold and warm ischemia in the isolated perfused rat liver. 817 41

Hepatic outcome after ischemia is compromised by anoxic injury and by release of oxygen free radicals or other pathological mediators at reperfusion. The platelet-activating factor (PAF) is an endogenous lipid-mediator which plays a key role in catalysing various pro-inflammatory processes. In this study the possible influence of platelet-activating factor antagonism was investigated on the integrity of the vascular endothelium, on free radical-mediated peroxidation and on post-ischemic functional outcome of the liver in the rat. Animals under pentobarbital anesthesia were subjected to 60 min of ischemia of the left and median liver lobes followed by 30 min of reperfusion in vivo. Pre-ischemic injection of the platelet-activating factor antagonist BN 52021 resulted in a significant reduction of endothelial enzyme loss into the plasma (purine nucleoside phosphorylase 56.2 vs. 83.1 U/l), and lowered hepatic lipid peroxidation (malondialdehyde 830 vs 932 nmol/g), leading to a significant improvement of postischemic bile flow and higher tissue levels of ATP. This suggests that the platelet-activating factor may play an important role in hepatic ischemia-reperfusion injury and that PAF antagonists like BN 52021 may be useful for clinical treatment.
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PMID:Platelet-activating factor antagonism enhances the liver's recovery from warm ischemia in situ. 822 31

This study was undertaken in order to assess the role of purely circulation-related effects upon free-radical-mediated reperfusion injury in the liver by comparing the respective effects of the oxygen free-radical scavenger superoxide dismutase (SOD) and the vasodilative action of papaverine in an ischemia/reperfusion model of the liver. Livers from male Wistar rats were rinsed blood free via the portal vein and stored ischemically (60 min at 37 degrees C in Krebs-Henseleit solution and 60 min at 4 degrees C in Euro-Collins solution). Reperfusion was carried out at a constant flow of 30 ml/min for 45 min at 37 degrees C in a nonrecirculating manner. Warm ischemic damage was evident in untreated livers compared to control livers, submitted solely to cold ischemia for 2 h at 4 degrees C, by increased vascular resistance upon reperfusion, enhanced enzyme leakage from the parenchyma (glutamate pyruvate transaminase, glutamate dehydrogenase) and from the endothelium (purine-nucleoside phosphorylase), reduced tissue content of ATP and enhanced lipid peroxidation. Preischemic treatment with SOD or papaverine (the latter also given during reperfusion) significantly reduced hepatic vascular resistance and parenchymal enzyme loss in a comparable manner. Both drugs resulted in a significant increase of hepatic tissue content of ATP at the end of reperfusion. SOD, but not papaverine, prevented the leakage of purine-nucleoside phosphorylase and significantly reduced the tissue levels of lipid peroxides.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of the hepatovasculature in free radical mediated reperfusion damage of the liver. 840 87

The hearts of young (6 months) and aged (24 months) rats, paced at a frequency of 300 bpm, were perfused by the Langendorff technique and subjected to: 20 min of equilibration perfusion, 30 min of global ischemia (95% reduction of the coronary flow) and 20 min of reperfusion. The control group was equilibrated for 20 min and then aerobically perfused for 50 min. After 20 min of stabilization, ATP and ADP levels and the adenine nucleotide pool were significantly higher in young than aged hearts (15% increase), but no modifications were found between the two age groups after 50 min of aerobic perfusion. Even the energy charge did not change under aerobic conditions. At the end of the ischemic period the levels of ATP and ADP decreased to a similar extent in young and aged hearts. After 20 min of reperfusion the myocardial level of ATP remained lower in comparison to the preischemic and control values in both age groups. At the end of the reperfusion there was a decrease in energy charge and creatine phosphate levels in the aged group in respect to the young group. The concentrations of adenosine, hypoxanthine and xanthine in coronary effluents did not change during ischemia and reperfusion irrespective of the age of the animals. On the contrary, the release of uric acid during ischemia and reperfusion was greater in aged than young hearts (90% increase). Moreover, the level of inosine in perfusates during the ischemic period was significantly lower in the 24-month-old group (30% decrease). These results are in accordance with the increased purine nucleoside phosphorylase activity and the decreased hypoxanthine phosphorybosyl-transferase activity found in the myocardium of the aged vs. young rats at the end of the reperfusion period. These data indicate that in the aged rat hearts, when exposed to ischemic and reperfusion conditions, there is a modification of purine breakdown which leads to a greater production of uric acid in respect to that found in young hearts.
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PMID:Age-dependent differences of ATP breakdown and ATP-catabolite release in ischemic and reperfused hearts. 846 22

The onset of warm ischemia and reperfusion injury in the liver was investigated in a canine model through changes in parenchymal markers [isozyme class V of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT)], endothelial markers [purine nucleoside phosphorylase (PNP) and hyaluronic acid clearance], and the liver metabolism (ketone body ratio) in warm ischemia induced by inflow occlusion using Pringle's maneuver and subsequent reperfusion. In this in vivo model, a PNP assay system and a model were designed so as to exclude the influence of wide localization of PNP possibly originating in erythrocytes or the intestine, and to discriminate between PNP of endothelial cells and that of parenchymal cells in the liver. After 45 min of warm ischemia, reperfusion resulted in damage only to endothelial cells, as seen by significant increase in PNP alone (3.6 +/- 0.1 U/liter at the end of warm ischemia to 6.8 +/- 0.5 U/liter at 5 min after reperfusion, P < 0.01) and significant decrease in hyaluronic acid clearance compared to the 30-min warm ischemia group in which no increase in either marker for parenchymal and endothelial cells was noted. By contrast, after 60 min of warm ischemia, reperfusion resulted in damage to parenchymal cells along with damage to endothelial cells, as seen by significant increases in LDH(V) and ALT (93 +/- 4 U/liter and 32 +/- 2 IU/liter at the end of warm ischemia to 239 +/- 17 U/liter and 165 +/- 27 IU/liter at 5 min after reperfusion, respectively), as well as a marked increase in PNP and deterioration of hyaluronic acid clearance compared to the 45-min warm ischemia group. Reperfusion after 120 min of warm ischemia did not show recovery of metabolic function of the liver as evaluated by hepatic mitochondrial redox state. It is suggested that a time lag occurs in the onset of injury between parenchymal cells and endothelial cells and that endothelial cells are temporally earlier in failing than parenchymal cells when the liver is exposed to short-term warm ischemia and subsequent reperfusion.
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PMID:Difference in onset of warm ischemia and reperfusion injury between parenchymal and endothelial cells of the liver. Evaluation by purine nucleoside phosphorylase and hyaluronic acid. 860 98

Activated Kupffer cells (KC) have been implicated in the damage sustained by preserved liver grafts during ischemia and reperfusion. The aim of this study was to compare ischemia/reperfusion injury in preserved, KC-depleted rat livers and preserved control livers, with special regard to sinusoidal endothelial cell (SEC) injury. Wistar rats were injected with liposome-encapsulated dichloromethylene diphosphonate, 48 hr before hepatectomy, to eliminate KC, or were withheld this pretreatment (controls). Livers were flushed with cold University of Wisconsin solution and after 0, 8, 16, or 24 hr of storage at 4 degrees C, were reperfused in a recirculation system with 200 ml of oxygenated Krebs-Henseleit solution at 37 degrees C for 90 min. Damage to SEC was measured by the uptake of hyaluronic acid (HA) from the perfusate and release of purine nucleoside phosphorylase (PNP). Perfusate samples were, furthermore, analyzed for aspartate aminotransferase (AST) and tumor necrosis factor-alpha. Carbon particles were infused in the perfusate to determine the phagocytotic capacity of KC. Biopsies were taken for histological examination and sections were stained with ED2 monoclonal antibodies to confirm the absence of KC. After 90 min of reperfusion, immediately after cold flush (t0), the uptake of HA was 72.2+/-2.3% and 69.3+/-1.3% in KC-depleted livers and in control livers, respectively (n.s.). After 8 hr of storage, HA uptake was 21.6+/-4.5% and 34.6+/-8.0%, respectively (n.s.). After 16 and 24 hr of storage and reperfusion, no uptake of HA was found in either KC-depleted or control livers, indicating abolished SEC function. PNP activities in the perfusate were higher in control livers (after 8 and 24 hr of storage), presumably due to release from damaged KC. No difference was found in AST and no tumor necrosis factor-alpha was measured in the perfusates of normal and KC-depleted livers. Electron microscopic studies showed that after 8 and 24 hr of storage and reperfusion, KC were activated and were able to phagocytose colloidal carbon. Our conclusion was that the elimination of Kupffer cells did not result in reduction of ischemic and reperfusion damage in livers preserved up to 24 hr, as assessed in vitro by SEC uptake of HA, PNP release, and AST release.
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PMID:No attenuation of ischemic and reperfusion injury in Kupffer cell-depleted, cold-preserved rat livers. 903 38


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