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

Toxic oxidants (oxygen free radicals) have been implicated in the formation of brain edema from ischemia-reperfusion injury or tumor growth. We investigated the ability of an iron chelator, a calcium channel blocker, and a xanthine oxidase inhibitor to reduce formation of brain edema following a cold lesion in cats. The agents were given independently of each other in an attempt to inhibit the Haber-Weiss reaction, prevent Ca++ modulated uncoupling of oxidative phosphorylation, and inhibit the generation of toxic oxidants via xanthine oxidase, respectively. Pentastarch-deferoxamine conjugate at a dose of 50 mg/kg was given 15 minutes before and 60 minutes after the cold lesion. Nimodipine was given at a dose of 1 mg/kg 1 hour before and 2 hours after the cold lesion. Allopurinol was given at a dose of 50 mg/kg 24 hours before, at the time of the lesion and, 24 and 48 hours after the lesion. Gravimetric measurements of multiple brain areas were performed at 24 hours post-lesion in the pentastarch-deferoxamine and nimodipine groups and at 72 hours post-lesion in the allopurinol group. None of these agents led to significant reduction in brain edema formation as measured with a gravimetric column of kerosene and bromobenzene. Pentastarch-deferoxamine conjugate was utilized to avoid the confounding effects of arterial hypotension which is seen with intravenous deferoxamine. There was even a suggestion of increased edema in the periventricular white matter in animals treated with nimodipine. Taken together, independent inhibition of the Haber-Weiss reaction, of calcium channels, or of xanthine oxidase does not reduce formation of brain edema in the cold lesion model.
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PMID:Proposed toxic oxidant inhibitors fail to reduce brain edema. 797 65

To determine the contribution of ischemia-reperfusion injury (IRI) to the blood flow deficit and hepatocellular dysfunction seen after resuscitation from hemorrhagic shock, the xanthine oxidase inhibitor allopurinol was given to rats as a 50 mg/kg bolus after shock but before resuscitation and continued as a 25 mg/kg/h infusion. Resuscitation with shed blood and lactated Ringer's restored cardiac output and blood pressure in both groups. Control animals demonstrated a reduction in total hepatic and effective hepatic blood flow to 59% and 43% of baseline values, respectively. Allopurinol resulted in a return to baseline values of both variables. Allopurinol treatment resulted in a 350% increase in xanthine, a 630% increase in hypoxanthine, and a 70% reduction in uric acid concentrations. These data suggest that IRI contributes to the organ dysfunction and blood flow deficits seen after resuscitated hemorrhagic shock the effect of which can be attenuated by the addition of the xanthine oxidase inhibitor allopurinol to standard resuscitation.
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PMID:Allopurinol plus standard resuscitation preserves hepatic blood flow and function following hemorrhagic shock. 799 11

Open chest dogs undergoing 30-min occlusion of the left anterior descending coronary artery (LAD), followed by 20-min reperfusion, received silibinin (2 mg/kg body weight), allopurinol (100 mg for two days as pretreatment, 20 mg/kg body weight during ischemia and reperfusion), superoxide dismutase (SOD, 5 and 0.5 mg/kg body weight, starting from the last minute of ischemia over 6 min). Control and treated dogs were comparable with respect to myocardial regional contractile force (strain gauge), malondialdehyde (MDA) and creatinine kinase (CK) levels of sinus coronarius blood samples, heart rate, and blood pressure. Allopurinol and large doses of SOD produced significant improvement in contractility and decreased MDA levels, which might suggest free radical mediated reactions during reperfusion.
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PMID:Effect of antioxidant treatment on the myocardium during reperfusion in dogs. 819 77

The effects of perfusate calcium reduction, allopurinol and dimethylthiourea on reperfusion-induced arrhythmias and purine wash-out in isolated rabbit and rat hearts were compared. The overall incidence of reperfusion-induced ventricular tachycardia (VT) was 88% and 94% and that of ventricular fibrillation (VF) was 44% and 88% in the control rabbit and rat hearts, respectively. VF was reduced to 10% and 0% in rat and rabbit hearts subjected to perfusate calcium reduction (0.4 mM for 1 min before ischemia and for 1 min before and throughout reperfusion), respectively. In allopurinol, 1 mM, perfused rat hearts the overall incidence of VF was not changed and only the incidence of a sustained VF (that lasting for at least 10 min) was reduced. VT and VF were prevented in allopurinol-perfused rabbit hearts. Dimethylthiourea, 10 mM, reduced the incidence of VF in rat hearts to 16% and did not significantly affect VT and VF in rabbit hearts. In untreated rat hearts, the major purine compounds washed out upon reperfusion were inosine, hypoxanthine, xanthine and urate. Allopurinol augmented the wash-out of adenosine and abolished that of xanthine and urate. In untreated rabbit hearts, the major purine washed out were inosine, adenosine and hypoxanthine. Allopurinol did not cause further increase in adenosine wash-out in rabbit hearts. We speculate that: (1) calcium mediated arrhythmogenic mechanism is operating both in reperfused rat and rabbit heart; (2) free radical mediated mechanism is of an importance only in rat heart; (3) neither a decreased free radical production secondary to xanthine oxidase inhibition nor the augmentation of adenosine wash-out is a likely explanation for the antiarrhythmic effect of allopurinol in reperfused hearts; and (4) high level of myocardial adenosine accumulation during ischemia, probably secondary to low xanthine oxidase activity, may play a role of a natural defence mechanism in ischemic/reperfused rabbit heart.
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PMID:Reperfusion arrhythmias and purine wash-out in isolated rat and rabbit heart. Effect of allopurinol, dimethylthiourea and calcium reduction. 823 Feb 46

The present study was undertaken to evaluate if allopurinol administration protects mice from bowel necrosis caused by temporary intestinal ischemia followed by indomethacin (INDO). We have previously reported that ischemia (15-minute occlusion of superior mesenteric vessels) followed by intravenous (i.v.) INDO caused significant bowel necrosis in CD-1 mice. Ischemia or INDO alone did not cause necrosis. To investigate protective measures against necrosis, we used CD-1 mice, 25 to 30 g. Forty-four animals were gavage fed 1 mL of water for 7 days and 32 animals were gavage fed 10 mg/kg allopurinol for 7 days. On the seventh day all animals were anesthetized and the superior mesenteric vessels occluded for 15 to 20 minutes, followed by i.v. INDO (0.5 mg/kg) once daily for 3 days. Animals who died were examined for bowel necrosis and all animals were killed 7 days after surgery and necropsied. Of the 44 saline-fed animals, 12 developed bowel necrosis (27%). Of the 32 allopurinol-fed animals, 1 developed necrosis (3%). The result of Fisher's exact two-tailed test was P = .006. Pretreatment with oral allopurinol significantly protects the mice from developing bowel necrosis when the mesenteric vessels are temporarily occluded and INDO is administered. Allopurinol may prevent reperfusion injury by inhibiting formation of xanthine oxidase generated, oxygen-derived free radicals and may be valuable in pretreating premature infants with patent ductus arteriosus who have had an ischemic episode in whom INDO use is contemplated.
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PMID:Allopurinol protects the bowel from necrosis caused by indomethacin and temporary intestinal ischemia in mice. 830 86

The effect of 5'-nucleotidase inhibitor (AMP-C) and xanthine oxidase inhibitor (Allopurinol: ALLO) on myocardial functional recovery and the restoration of myocardial high energy phosphates after 15 min of normothermic global ischemic insult, was studied in the isolated isovolemic Langendorff rat heart model. Fifty nine rats were divided into 4 groups: Group I; saline, Group II; AMP-C plus ALLO, Group III; AMP-C, Group IV; ALLO. Intermittent infusion of drugs was delivered in 3 ml of solution at 5 min intervals during ischemia. Percent recovery of left ventricular systolic function was as follows: Group I; 74.2 +/- 3.6%, Group II; 87.7 +/- 1.7%, Group III; 83.5 +/- 3.1%, Group IV; 86.4 +/- 2.6%. Improved recovery was statistically significant only in Group II (p < 0.05 vs Group I). Suppression of reactive hyperemia was seen with reperfusion in the groups which had been treated with AMP-C (i.e., Groups II and III). Myocardial adenine nucleotides and purines were measured in 6 hearts in each group using high performance liquid chromatography. Myocardial ATP levels was 0.89 +/- 0.16 nmol/mg left ventricular wet weight in Group I, 1.37 +/- 0.12 in Group II (p < 0.05 vs Group I), 1.42 +/- 0.17 in Group III (p < 0.05) and 1.17 +/- 0.15 in Group IV. This study demonstrates that intermittent infusion of AMP-C plus ALLO during global myocardial ischemia results in improved myocardial functional recovery and improved preservation of high energy phosphates.
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PMID:Evaluation of the effectiveness of 5'-nucleotidase inhibitor and allopurinol in myocardial ischemia. 835 99

The effect of Allopurinol on energy metabolism (re-utilisation of hypoxanthine) was studied in a in vivo skeletal muscle ischemia rat model by 31-P-MR spectroscopy. Allopurinol-treatment showed no benefit to the kinetics of PCr/(Pi + PCr) and ATP/(Pi + PCr). The role of re-utilisation of hypoxanthine has to be further investigated.
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PMID:[Modification of ischemia and reperfusion damage of skeletal muscles with allopurinol: in vivo 31P MR spectroscopy of the posterior limb of the rat]. 837 57

Leukocyte adhesion may play a central role in the pathogenesis of preservation-reperfusion injury to liver grafts. We previously showed that lymphocyte adhesion to sinusoids is dependent on the length of cold ischemia. In the present study we examined the mechanisms of lymphocyte adherence after harvesting combined with a short and a long preservation time. The effects of lymphocyte adherence on liver function were also examined. Rat livers were stored at 1 degrees C in University of Wisconsin solution for 45 min or 30 hr and then reperfused at 37 degrees C in the isolated perfused rat liver with isogeneic lymphocytes in an asanguineous perfusate. The role of reactive oxygen intermediates was investigated with allopurinol, a vitamin E analog and ascorbate or superoxide dismutase and catalase. For us to determine the role of Kupffer cells, Kupffer cell blockade was produced by gadolinium chloride. Leukotriene B4 effects were examined with the lipooxygenase inhibitor, nordihydroguaiaretic acid. We evaluated the possible presence of mechanical obstruction by studying flow rates and the circulation of red blood cells. We examined the role of adhesion molecules by pretreating lymphocytes with trypsin or neuraminidase and by exposing livers to arabinogalactan. We investigated the effects of lymphocyte adhesion on liver function by comparing perfusate liver enzymes in livers reperfused with and without lymphocytes, with trypsinized lymphocytes and with an increased number of lymphocytes. Allopurinol significantly reduced hypoxanthine degradation, and nordihydroguaiaretic acid inhibited leukotriene B4 release into the perfusate. The ability of gadolinium chloride to inhibit Kupffer cells was shown by colloid carbon uptake. In livers harvested and preserved for 45 min, lymphocytes decreased about 40% during reperfusion. In livers preserved for 30 hr, the reduction was significantly greater (about 80%). Lymphocyte adherence was lessened in livers preserved for 45 min by all three of the reactive oxygen intermediate protectants and by gadolinium chloride. In contrast, neither reactive oxygen intermediate protectants nor gadolinium chloride reduced adherence in livers preserved for 30 hr. Nordihydroguaiaretic acid had no effect in livers preserved for either 45 min or 30 hr. Portal flow in livers preserved for 45 min and 30 hr was similar, suggesting an absence of mechanical obstruction, and this finding was supported by a complete absence of red cell trapping. Trypsinization of lymphocytes and exposure of livers to arabinogalactan significantly lessened lymphocyte adherence in livers preserved for 30 hr but not in those preserved for 45 min.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lymphocyte adherence in the reperfused rat liver: mechanisms and effects. 838 Jul 89

The peroxidation of lipids and changes in the activities of related enzymes, such as xanthine-xanthine oxidase (XOD), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) in the gastric mucosa were studied in rat model of ischemia-reperfusion with pylorus ligation. Myeloperoxidase (MPO), a marker enzyme of leucocytes, was also studied. Thiobarbituric acid reactive substances (TBA RS) in gastric mucosa were significantly increased by clamping the celiac artery for 30 min and reperfusion for 60 min after 3 h of pylorus ligation. XOD activity in gastric mucosa increased with the development of gastric mucosal injury. Allopurinol significantly suppressed XOD activity but did not inhibit mucosal injury or the increase in TBA RS. MPO activity in the gastric mucosa was significantly increased by gastric mucosal injury. Famotidine significantly inhibited the increase in MPO activity in gastric mucosa, while allopurinol did not. SOD and GSH-px activities in the gastric mucosa were decreased significantly by gastric mucosal injury. SOD activity was normal following treatment with famotidine and allopurinol. Moreover, GSH-px activity recovered to the normal level with famotidine and allopurinol treatment. These findings suggest that oxygen radicals and lipid peroxidation can cause gastric mucosal injury by ischemia-reperfusion in the pylorus-ligated rat. The generation of oxygen free radicals may be derived mainly from activated polymorphonuclear leukocytes (PMN), and the decrease in SOD and GSH-px activity in gastric mucosa seems to aggravate mucosal injury by free radicals and lipid peroxidation.
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PMID:Role of lipid peroxidation in gastric mucosal lesions induced by ischemia-reperfusion in the pylorus-ligated rat. 839 87

This study was aimed at examining the vulnerability of the liver to oxygen-free radicals upon reoxygenation after prolonged ischemia. Livers from male Wistar rats were first flushed with Ringer's and Euro-Collins solutions. After ischemic storage in Krebs-Henseleit solution at 37 degrees C for 60 min and in Euro-Collins solution at 4 degrees C for another 60 min, they were then persufflated with either gaseous O2 or N2 for 30 min at 37 degrees C, and rinsed again with Ringer's solution. Enzyme concentrations and calcium ion activities were measured in the effluent rinsing solution after passage through the liver. Treatment with superoxide dismutase (SOD) or allopurinol resulted in a significant reduction of tissue injury, determined by the enzyme loss, calcium uptake, and lipid peroxidation upon persufflation with O2. Allopurinol also improved the tissue levels of ATP and the sum of adenine nucleotides after aerobic persufflation, whereas SOD did not. Notwithstanding, neither treatment had any effect on anoxic persufflation with N2. Thus, we conclude that the postischemic liver is susceptible to oxygen-induced free radical injury and that allopurinol and SOD promote specific antioxidative protection of the liver, with the exclusion of side effects related to substrates or perfusion modalities.
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PMID:The effects of allopurinol and SOD on lipid peroxidation and energy metabolism in the liver after ischemia in an aerobic/anaerobic persufflation. 840 Jun 77


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