allopurinol and Arterial-Occlusive-Diseases

The influence of a temporary occlusion of the superior mesentery artery on the generation of oxygen free radical products was tested in controls and after administration of perflubron. The occlusion time lasted for 90 min and a reperfusion time of 150 min was chosen until examination of tissue samples took place. The content of thiobarbituric acid reactive substances (TBARS), glutathione (GSH) and myeloperoxidase (MPO) was determined in homogenized tissue samples. A protective effect of antioxidants or radical scavengers was tested in form of alpha-tocopherol and allopurinol. A highly significant increase of TBARS was found in the operated control group, still higher under perflubron (perfluoroocytylbromide, PFOB). However, under alpha-tocopherol as well as under allopurinol the effect of radical products could be diminished below the values of controls. GSH and MPO were not significantly changed under PFOB as compared to the operated control group.

Topics: Allopurinol; Animals; Antioxidants; Arterial Occlusive Diseases; Emulsions; Fluorocarbons; Free Radical Scavengers; Free Radicals; Glutathione; Hydrocarbons, Brominated; Male; Mesenteric Artery, Superior; Oxygen; Peroxidase; Rats; Rats, Wistar; Shock; Thiobarbituric Acid Reactive Substances; Vitamin E

The aim of this study was to assess the effect of allopurinol on rat groin flaps rendered ischaemic by selectively occluding the feeding femoral artery and reperfused by means of microsurgical anastomosis. For the establishment of the critical arterial ischaemia time, the femoral artery of 29 rat groin flaps isolated on the inferior epigastric pedicle was occluded for 10, 12 and 14 h. Following 12 h or more of ischaemia, 5.25% of the flaps survived, compared to 40% survival after 10 h (p = 0.04). In the second stage of the study, 34 rat groin flaps were subjected to arterial ischaemia for 12 h. Of these, 12 rats received allopurinol solution I.V. 30 min prior to reperfusion, 10 received the vehicle solution (control) and 12 underwent no treatment (control). After 7 days, survival of the groin flaps was observed in 41.7%, 0 and 8.3% of the groups, respectively (p = 0.0164). This study suggests that systemic administration of allopurinol has a beneficial effect on rat arterial ischaemic groin flaps and may prolong their critical ischaemia time.

Topics: Allopurinol; Animals; Arterial Occlusive Diseases; Female; Graft Survival; Ischemia; Rats; Skin; Surgical Flaps; Time Factors

Free radicals have been shown to play an important role in ischemia-reperfusion injury in several organ systems; however, the role of free radicals in central nervous system ischemia has been less well studied. Many potential free radical-generating systems exist. The primary products of these reactions, superoxide and hydrogen peroxide, may combine to produce hydroxyl radicals. Of the many potential sources of free radical generation, the enzyme xanthine oxidase has been shown to be important in ischemia in noncerebral tissue. We investigated the effect of the hydroxyl radical scavenger dimethylthiourea and the xanthine oxidase inhibitor allopurinol on infarct volume in a model of continuous partial ischemia. Male Sprague-Dawley rats were treated with dimethylthiourea or allopurinol before middle cerebral artery occlusion. Infarct volume was measured by triphenyltetrazolium chloride staining of brains removed 3 or 24 hours after occlusion. Stroke volume was reduced by 30% after dimethylthiourea treatment and by 32-35% after allopurinol treatment. At 24 hours after stroke, cortical tissue was more effectively protected than caudate tissue with both agents. Pretreatment with dimethylthiourea and allopurinol also significantly reduced cerebral edema formation and improved blood-brain barrier function as measured by fluorescein uptake. Our results imply that hydroxyl radicals are important in tissue injury secondary to partial cerebral ischemia and that xanthine oxidase may be the primary source of these radicals.

Topics: Allopurinol; Animals; Arterial Occlusive Diseases; Blood-Brain Barrier; Brain Chemistry; Cerebral Arteries; Cerebral Infarction; Disease Models, Animal; Drug Evaluation, Preclinical; Male; Rats; Rats, Inbred Strains; Staining and Labeling; Stroke Volume; Thiourea; Time Factors

Pre-treatment with allopurinol is able markedly to attenuate the deterioration in blood viscosity (BV) and whole blood filterability (WBF) that occurs after ischaemia during exercise. It also reduces the exercise-induced increase in serum oxidase activity, although this action is slightly less effective in peripheral obliterative arterial disease (POAD) patients. Conversely, allopurinol is completely ineffective in modifying haemorheological parameters in vitro, and it does not affect superoxide anion generation or enzyme release from neutrophils stimulated in vitro with formyl-methionyl-leucyl-phenylalanine (FMLP). It is suggested that allopurinol may attenuate changes in BV and WBF by affecting xanthine-oxidase-dependent free radical formation in tissues.

Topics: Aged; Allopurinol; Arterial Occlusive Diseases; Blood Viscosity; Coronary Disease; Female; Glucuronidase; Humans; In Vitro Techniques; Male; Middle Aged; Neutrophils; Physical Exertion; Rheology; Superoxides

This study assessed the contribution of angiotensin II, oxygen-free radicals, and vasopressin to the mortality of acute mesenteric ischemia in rats. Rats received saline replacement (16 ml/kg/hr) for 3 hr during and after 85 min of superior mesenteric artery (SMA) occlusion. Only 21% of rats that received saline alone (n = 14, control) survived 48 hr, significantly less than the 100% survival of sham-operated rats (no SMA occlusion, n = 5, P less than 0.01). Neither teprotide (an angiotensin converting-enzyme inhibitor), allopurinol (to reduce oxygen-free radical formation), nor a specific vasopressin antagonist [1-(beta-mercapto-beta,beta-cyclopentamethyleneproprionic acid), 2-(O-methyl) tyrosine arginine-vasopressin] improved 48-hr survival, which was 17% in each group (n = 6, each). Survival improved significantly to 86% (n = 7, P less than 0.001) when intravenous glucagon (1.6 micrograms/kg/min) was given for 2 hr after SMA reperfusion. Survival after dopamine infusion (12 micrograms/kg/min iv) was 67% at 48 hr, a nearly significant improvement (n = 9, P less than 0.06). These results suggest that angiotensin II, oxygen-free radicals, and vasopressin do not contribute significantly to the high mortality observed after acute intestinal ischemia in this rat model, but that glucagon, and to a lesser extent, dopamine, are potentially therapeutic.

Topics: Allopurinol; Animals; Arterial Occlusive Diseases; Dopamine; Glucagon; Ischemia; Male; Mesenteric Arteries; Rats; Rats, Inbred Strains; Teprotide

Occlusion of the pulmonary arterial circulation to a lung for prolonged periods has been reported to result in only minimal alterations in lung morphology. We studied the effects of 48 h of pulmonary arterial occlusion followed by 4 h of reperfusion in 18 awake dogs. Because of evidence in other organ systems of O2 radical generation, during reperfusion, nine of the animals were randomly assigned to receive allopurinol, a xanthine oxidase inhibitor, and vitamin E, an antioxidant. Reperfusion resulted in marked edema and inflammatory infiltrates in the reperfused lung but also caused mild edema and inflammation in the contralateral continuously perfused lung. Electron microscopy demonstrated lysis of both capillary endothelial and alveolar epithelial cells bilaterally, with the frequency of cell injury greater on the reperfused side. During reperfusion, body temperatures rose dramatically from 39.4 +/- 0.1 to 40.6 +/- 0.2 degrees C (P less than 0.05) and marked leukopenia developed. There were no differences in any hemodynamic, gas exchange, or morphometric measurements between allopurinol-treated dogs and untreated animals. We conclude that reperfusion causes local and distant injury which does not appear to be mediated by xanthine oxidase-produced O2 radicals.

Topics: Allopurinol; Animals; Arterial Occlusive Diseases; Blood Pressure; Carbon Dioxide; Cardiac Output; Dogs; Heart Rate; Hemodynamics; Lung; Microscopy, Electron; Oxygen; Partial Pressure; Perfusion; Pulmonary Artery; Pulmonary Circulation; Vitamin E