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)

Uric acid (UA) in the rat brain was measured by HPLC with an electrochemical detector following focal ischemia. At 24 h after the operation, the UA level in the ischemic center was 105.47 +/- 8.39 nmol/g tissue, whereas it was 8.36 +/- 1.86 in the sham-operated group. Allopurinol, xanthine oxidase inhibitor, almost completely inhibited this UA accumulation. These data demonstrate that the UA increase in the ischemic brain is due to the xanthine oxidase reaction.
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PMID:Allopurinol inhibits uric acid accumulation in the rat brain following focal cerebral ischemia. 280 84

Growing evidence supports the concept that oxygen free radicals are an important cause of myocardial ischemic and reperfusion injury. This study was designed to determine if toxic oxygen metabolites may exacerbate ischemic injury upon reoxygenation. Left ventricular function was studied in a group of seven dogs receiving intermittent, 4 degrees C, hyperosmolar, hyperkalemic (KCI 25 mEq/L) saline cardioplegic solution. This group was compared to a group (n = 7) receiving a hyperkalemic (KCI 25 mEq/L) cardioplegic solution designed to scavenge superoxide anion and hydroxyl radical: superoxide dismutase (3,000 U/ml) and mannitol (325 mOsm/L). A third group of five animals received allopurinol pretreatment (50 mg/kg/day) for 72 hours and hyperkalemic saline cardioplegic solution. After 60 minutes of ischemia (10 degrees to 15 degrees C) and 45 minutes of reperfusion, left ventricular mechanical function was better in the groups receiving free radical scavengers and allopurinol pretreatment than in the group receiving only hyperkalemic saline cardioplegic solution. Free radical scavengers preserved myocardial function in this model of hypothermic global ischemia and reperfusion. Our data support the concept that injury occurs primarily during reperfusion with the generation of oxygen free radicals via the hypoxanthine-xanthine oxidase reaction. Allopurinol has potential clinical application in the prevention of reperfusion injury.
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PMID:Prevention of free radical-induced myocardial reperfusion injury with allopurinol. 298 20

Reactive oxygen species generated by xanthine oxidase during reperfusion of ischemic liver might in part be responsible for ischemic organ injury. Therefore, the effect of allopurinol, an inhibitor of xanthine oxidase, on the oxidant stress associated with reperfusion and on hepatic function 24 h after ischemia was assessed in a model of partial hepatic ischemia in rats. The increase in circulating glutathione disulfide (GSSG) was used as an index of oxidant stress. Hepatic function was assessed using a breath test to quantitative the demethylation of aminopyrine in vivo. In control animals the plasma concentration of GSSG 1 h after onset of reperfusion increased from 0.9 mumol/l in sham-operated controls to 4.2, 5.5, and 8.0 mumol/l following 45, 90 and 120 min of ischemia, respectively. The percent of the administered dose of (dimethylamine-14C)-aminopyrine appearing in breath as 14CO2 was not significantly different from sham-operated controls (40.2%) 24 h after 45 min of ischemia (34.1%), but decreased progressively to 26.0% (p less than 0.05) and 20.6% (p less than 0.05) after 90 and 120 min of ischemia, respectively. Allopurinol, administered at a dose of 50 mg/kg 18 h and 1 h prior to ischemia, did not prevent the rise in plasma GSSG, did not alleviate the release of transaminases, and did not improve the demethylation of aminopyrine 24 h after ischemia, suggesting that reactive oxygen species generated by xanthine oxidase during reperfusion of ischemic liver do not contribute significantly to ischemic injury.
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PMID:Effect of allopurinol on oxidant stress and hepatic function following ischemia and reperfusion in the rat. 321 73

To determine the role of free radical-induced injury during heart preservation and transplantation, we harvested hearts from 28 mongrel dogs (12.5 to 16.5 kg), divided them into four groups, and orthotopically transplanted them. A group of seven hearts were orthotopically transplanted immediately after excision (group A). A second group of seven animals received allopurinol pretreatment (50 mg/kg/day) for 72 hours, and the hearts were orthotopically transplanted immediately after excision (group B). A third group of seven hearts were transplanted after continuous perfusion with oxygenated modified Collins solutions at 4 degrees C, pH 7.4, and a pressure of 20 mm Hg for 18 hours (group C). A fourth group of seven animals received allopurinol pretreatment (50 mg/kg/day) for 72 hours, and the hearts were orthotopically transplanted after perfusion with modified Collins solutions in the same manner as group C hearts (group D). The generation of free radicals, estimated by measurement of thiobarbituric acid reactive substances (malondialdehyde) in the coronary effluent, stayed at low levels during perfusion in groups C and D and also remained at low levels during operational ischemia in group A and B. During reperfusion, their levels abruptly and significantly increased and were associated with a corresponding increase in creatinine kinase MB isoenzyme (malondialdehyde levels at 30 minutes' reperfusion: A, 2.25 +/- 0.43; B, 1.55 +/- 0.25 nmol/ml/100 gm wet weight [p less than 0.05 versus group A]; C, 2.67 +/- 0.28; D, 1.77 +/- 0.27 nmol/ml/100 gm wet weight [p less than 0.05 versus group C]). In the allopurinol pretreatment groups, allopurinol significantly slowed the appearance of malondialdehyde and the release of creatinine kinase MB isoenzyme during reperfusion. Furthermore, cardiac functions during reperfusion, expressed as percent of control (mean +/- standard deviation), were significantly better in the allopurinol pretreatment groups than in the untreated groups: maximum first derivative of left ventricular pressure: A, 76.4 +/- 9.5; B, 99.7 +/- 14.3 [p less than 0.05 versus group A]; C, 25.2 +/- 2.6; D, 42.7 +/- 7.9 [p less than 0.05 versus group C]). These results indicate that (1) the generation of oxygen free radical is not significant during perfusion with modified Collins solutions nor during operational ischemia, but only during reperfusion, and (2) allopurinol reduces free radical-induced injury during reperfusion. Allopurinol has potential application in the prevention of reperfusion injury during heart transplantation.
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PMID:Prevention of free radical-induced myocardial injury by allopurinol. Experimental study in cardiac preservation and transplantation. 327 69

Allopurinol, a competitive inhibitor of xanthine oxidase, has been shown to have a protective effect on ischemic myocardium, but its mechanism of action remains controversial. We used an isolated rat heart preparation to test the hypothesis that allopurinol could restore adenosine triphosphate (ATP) levels and improve the recovery of left ventricular function after global myocardial ischemia. Hearts were equilibrated for 30 min, subjected to 10 min of global, normothermic (37 degrees C) ischemia, and reperfused for 15, 30, and 60 min. Hearts treated with allopurinol (100 microM) exhibited greater ATP levels and improved function during reperfusion than did untreated control hearts. Hearts treated with hypoxanthine (100 microM), the substrate for xanthine oxidase, also showed increased ATP and functional recovery compared with controls. These results suggest that allopurinol may protect the globally ischemic myocardium by enhancing the salvage of hypoxanthine for reincorporation into adenine nucleotides.
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PMID:Allopurinol enhanced adenine nucleotide repletion after myocardial ischemia in the isolated rat heart. 333 32

Experiments were performed to test whether the reduction in infarct size afforded by allopurinol following 24 h of permanent coronary artery occlusion is sustained over the subsequent 24 h. A dog's coronary artery was occluded with an embolus followed by injection of radiomicrospheres into the left ventricle to mark the ischemic region and to measure regional blood flow. Dogs were sacrificed either 24 h or 48 hours after embolization. The infarcts were delineated by failure to stain with triphenyl tetrazolium chloride and the ischemic zones were visualized by autoradiography of the heart slices. Dogs in the treatment groups received 600 mg of allopurinol PO 18 h before surgery, and a 10 mg/kg IV bolus 15 minutes before embolization followed by constant IV infusion of 55 mg/kg/24 h until sacrifice. A close correlation in the control animals between the percent of the ischemic zone which infarcted and collateral blood flow was used to predict a nonintervention infarct size in each treatment animal. Allopurinol treatment caused 17.9 +/- 3.3% less of the risk zone to be tetrazolium negative after 24 hours of ischemia than that seen in untreated animals. Less allopurinol induced salvage was observed in the 48 hour drug group with only a 11.1 +/- 3.3% limitation in infarct size. Furthermore, the effect was inconsistent at 48 h with only 2 dogs showing salvage. We conclude that allopurinol delays but does not prevent infarction in the permanent occlusion model.
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PMID:Protection afforded by allopurinol in the first 24 hours of coronary occlusion is diminished after 48 hours. 334 99

The separate roles of exogenous acid, ischemia, and retransfusion of shed blood on gastric lesion formation in the rat hemorrhagic shock model were studied. In addition, the role of oxyradicals in lesion formation in this model was studied. Intragastric HCl increased gastric mucosal lesion formation in a dose-dependent manner. Even in the absence of intragastric HCl, ischemia followed by retransfusion of shed blood caused histologic mucosal injury in the corpus and antrum. Allopurinol, a xanthine oxidase inhibitor that prevents oxyradical formation, slightly, but significantly, reduced the gastric mucosal injury induced by ischemia-reperfusion but not that induced by ischemia alone. There was no significant difference in the extent of damage caused by ischemia-reperfusion and ischemia alone. We conclude that exogenous acid, ischemia, and oxyradical formation after retransfusion of shed blood are all important interacting factors in the rat hemorrhagic shock model of gastric mucosal injury. Allopurinol, by inhibiting formation of the oxyradical component, significantly protects against the injury.
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PMID:Role of exogenous acid and retransfusion in hemorrhagic shock-induced gastric lesions in the rat. 335 Feb 82

Allopurinol has been shown to provide significant protection against ischemia/reperfusion-induced microvascular and parenchymal cell injury. It has been hypothesized that the protection seen with allopurinol after ischemia/reperfusion (I/R) is caused by inhibition of xanthine oxidase. However, recent reports suggest that the beneficial effects of allopurinol in I/R may be caused by direct free radical scavenging. The objective of this study was to determine whether the regimen of allopurinol administration used in most I/R studies leads to a significant modification of the free radical scavenging properties of extracellular fluid (ECF), i.e., plasma and lymph. Plasma and intestinal lymph samples obtained from both control and allopurinol-treated cats were used to assess the following: 1) allopurinol and oxypurinol concentrations, 2) xanthine oxidase inhibition, 3) myoglobin-catalyzed linolenic acid peroxidation, 4) hypochlorous acid scavenging, and 5) protein and nonprotein sulfhydryl content. ECF from allopurinol-treated animals contained approximately 10 microM each of allopurinol and oxypurinol. Ten percent ECF resulted in 80% inhibition of xanthine oxidase activity. Comparable volumes of control ECF did not inhibit xanthine oxidase. Furthermore, allopurinol treatment did not enhance the antioxidant properties of ECF. The results of this study do not support the contention that the beneficial effects of allopurinol in I/R injury are caused by the scavenging of oxidants produced in ECF by activated granulocytes.
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PMID:Allopurinol does not enhance antioxidant properties of extracellular fluid. 339 21

Allopurinol is thought to protect hearts against damage due to hypoxia or ischemia by inhibiting xanthine oxidase and oxygen radical generation. We subjected isolated rabbit hearts, equilibrated by perfusion at 37 degrees C, to 1 h of global ischemia at 27 or 37 degrees C with or without brief pretreatment with 100 microM allopurinol. The total absence of xanthine or uric acid in the coronary effluent following ischemia, the presence of hypoxanthine (25 +/- 4 microM peak concentration), and the failure of allopurinol to alter purine washout profiles or postischemic cardiac function suggest that rabbit myocardium lacks xanthine oxidase or dehydrogenase. Data obtained with a similar rat heart preparation showed appreciable formation of xanthine (12 +/- 2 microM peak) and uric acid (10 +/- 3 microM). Allopurinol pretreatment inhibited xanthine and uric acid formation and significantly improved key indicators of postischemic left ventricular function. We conclude that there is species dependency in the myocardial activity of xanthine oxidase or dehydrogenase, that when present it can be inhibited by acute allopurinol pretreatment, and that xanthine oxidase activity and its ability to generate oxygen radicals are not universal contributors to cardiac ischemic damage.
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PMID:Purine efflux after cardiac ischemia: relevance to allopurinol cardioprotection. 381 51

The pathogenic mechanisms responsible for heart damage following temporary coronary artery occlusion are unknown. Some damage may be mediated by a normal cellular enzyme, xanthine dehydrogenase, which converts to xanthine oxidase during myocardial ischemia. Reperfusion, with restoration of oxygen supply, may then lead to formation of superoxide by xanthine oxidase, possibly initiating a cascade of oxidative events. In support of this, reperfusion of transiently ischemic canine myocardium leads to a rapid loss of cellular glutathione and a decrease in catalase activity, both indicative of enhanced generation of activated oxygen. Allopurinol--an inhibitor of xanthine oxidase--ameliorates both biochemical damage and functional deficits ordinarily triggered by ischemia and reperfusion, suggesting one possible mode of pharmacologic intervention following acute myocardial infarction.
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PMID:Reactive oxygen species may cause myocardial reperfusion injury. 383 75


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