allopurinol and Shock

Acute tubular necrosis is a frequent occurrence following hypovolemic shock and human renal transplantation. Although this postischemic injury was originally thought to result from ischemia alone, it has recently been recognized that significant tissue injury can occur during the period of reperfusion. The demonstration of the oxygen free-radical-mediated postischemic reperfusion injury by Granger, Rutili, and McCord in ischemic cat intestine suggested that this mechanism might also be operative following renal ischemia. In the kidney, postischemic injury results in necrosis of the proximal renal tubule and accumulation of erythrocytes in the outer renal medulla. It has been proposed that the primary event leading to these pathologic changes is a free-radical-mediated injury to the endothelial cells in the inner stripe of the outer medulla. Experimental evidence in animals subjected to warm and cold ischemia supports a free-radical-mediated mechanism. The clinical significance of these findings is demonstrated in preclinical animal studies of renal transplantation in which approximately two-thirds of the injury following cold ischemia could be ablated by superoxide dismutase administered just prior to reperfusion or by allopurinol when administered both at the time of preservation and reperfusion or at the time of preservation alone.

Topics: Acute Kidney Injury; Allopurinol; Animals; Cats; Free Radicals; Humans; Ischemia; Kidney; Kidney Transplantation; Kidney Tubular Necrosis, Acute; Perfusion; Postoperative Complications; Rabbits; Rats; Shock; Superoxide Dismutase; Temperature; Xanthine Oxidase

It is now clear that oxygen-derived free radicals play an important part in several models of experimentally induced reperfusion injury. Although there are certainly multiple components to clinical ischemic and reperfusion injury, it appears likely that free-radical production may make a major contribution at certain stages in the progression of the injury. The primary source of superoxide in reperfused reoxygenated tissues appears to be the enzyme xanthine oxidase, released during ischemia by a calcium-triggered proteolytic attack on xanthine dehydrogenase. Reperfused tissues are protected in a variety of laboratory models by scavengers of superoxide radicals or hydroxyl radicals or by allopurinol or other inhibitors of xanthine oxidase. Dysfunction induced by free radicals may thus be a major component of ischemic diseases of the heart, bowel, liver, kidney, and brain.

Topics: Animals; Calcium; Coronary Disease; Free Radicals; Humans; Intestines; Ischemia; Shock; Superoxides; Transplantation; Xanthine Dehydrogenase; Xanthine Oxidase

The initial cellular reaction against the deleterious effects of shock-inducing stimuli apparently elevates the energy-producing capacity so that the cell is able to sustain its normal function. Several endocrine events are fundamentally important as triggering factors for this kind of reaction. As the shock state advances, cellular metabolism deteriorates progressively and cellular energy is exhausted. Depression of intracellular cAMP may induce cellular metabolic unresponsiveness to hormonal stimuli. Consistent degradation of high-energy substances, extreme deviation of the redox state in the NAD+-NADH system, and decrease of endogenous key substances such as L-carnitine ultimately may lead to a standstill of cellular enzymatic reactions (Fig. 13). Methods intended to sustain cellular membrane and enzymatic systems may offer the best contribution to the improvement of shock therapy.

Topics: Adenine Nucleotides; Allopurinol; Animals; Bucladesine; Carnitine; Cyclic AMP; Cytoplasm; Energy Metabolism; Humans; Kidney; Liver; Oxidation-Reduction; Rabbits; Rats; Shock; Shock, Hemorrhagic

Oxygen radicals appear to be involved in the microvascular and parenchymal cell injury associated with various pathologic disorders. Studies indicate that oxygen radicals increase microvascular permeability by creating large leakage sites predominantly in the small venules. The highly reactive hydroxyl radical appears to be responsible for the microvascular alterations associated with oxygen radical production. There is considerable indirect evidence implicating oxygen radicals in the pathogenesis of circulatory shock. The oxygen radicals are probably formed by the enzyme xanthine oxidase when intravascular volume is restored. Similar biochemical processes appear to be involved in reperfusion injury to the kidney and skin. Evidence is also presented that implicates oxygen radicals in the reperfusion injury associated with organ preservation and transplantation.

Topics: Animals; Cricetinae; Dogs; Free Radicals; Ischemia; Kidney; Microcirculation; Organ Preservation; Oxygen; Rats; Shock; Skin; Skin Transplantation; Surgical Flaps; Tissue Preservation; Xanthine Oxidase

This study investigated whether the free radical scavengers allopurinol (50 mg p.o. q.i.d.) and dimethyl sulphoxide (DMSO, 500 mg p.o. q.i.d.) influence the incidence of stress-induced acute gastric mucosal injury in patients with pelvic fractures and hypovolaemic shock. In 177 fully evaluable patients (control n = 58, allopurinol n = 62, DMSO n = 57), endoscopically proven stress-induced injury evolved in a significantly (p less than 0.01) larger number of controls relative to either group on active therapy. During the first 3 days after hospitalization, 13 controls (22%) developed the injury whereas only 2 patients in each of the allopurinol (3%) and DMSO (4%) groups had this injury. Of these cases, 8 controls (14%) and one patient in the allopurinol group (2%) deteriorated and underwent emergency surgery, however 3 of the controls (5%) died in the immediate post-operative period. The results suggest that oxygen-derived free radicals are directly implicated in stress-induced acute gastric mucosal injury and that removing them protects against this injury and its complications.

Topics: Adolescent; Adult; Aged; Allopurinol; Dimethyl Sulfoxide; Double-Blind Method; Female; Fractures, Bone; Free Radicals; Gastric Mucosa; Humans; Male; Middle Aged; Pelvic Bones; Peptic Ulcer; Prognosis; Prospective Studies; Shock

This study aimed to evaluate the relation between apoptosis of enterocytes and oxygen-free radical injury in scalded rats with delayed resuscitation as well as the role of antioxidants in the prevention of enterocyte apoptosis.. For this study, 150 male Wistar rats were divided randomly into four groups representing early resuscitation (ER), delayed resuscitation (DR), N-acetylcysteine (NAC) treatment, and allopurinol (Allo) treatment. The animals were subjected to a 30% total body surface area, full-thickness scald. Fluid therapy was started 6 hours after the injury in the DR and treatment groups. Apoptosis of enterocytes was identified by DNA fragmentation (ap%), DNA agarose gel electrophoresis, and terminal deoxynucleotidyl transferace (TdT)-mediated dUPT-biotin nick end labeling (TUNEL). The contents of malondialdehyde (MDA), total sulfhydryl (TSH), and nonprotein sulfhydryl (NPSH) and the activity of xanthine oxidase in intestinal mucosa were determined after the burn in the four groups.. Apoptosis of enterocytes increased significantly in all the groups. The animals in the DR group showed an earlier and greater increase in ap% than the animals in the ER group. Similar results were seen for electrophoresis, TUNEL assay, and levels of MDA, xanthine oxidase (XO), TSH, and NPSH. Treatment with NAC was associated with a decrease in ap% and MDA, but not XO, as compared with the levels in the DR group, whereas treatment with Allo was associated with a decrease in MDA and XO, but not ap%. Delayed resuscitation was associated with significant decreases in TSH and NPSH, as compared with the levels in the ER group, whereas both the NAC and Allo groups had significantly higher levels of TSH and NPSH than the DR group.. Significant apoptosis of enterocytes was induced by oxidative stress in the intestinal mucosa after a burn in rats. The findings show that NAC blunted intestinal apoptosis induced by oxygen-free radical, which was generated in the process of ischemia-reperfusion injury after a burn because of delayed resuscitation.

Topics: Acetylcysteine; Allopurinol; Animals; Apoptosis; Burns; DNA Fragmentation; Enterocytes; Glutathione; Ilium; In Situ Nick-End Labeling; Intestinal Mucosa; Male; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury; Resuscitation; Shock; Xanthine Oxidase

We have shown previously that rats subjected to tourniquet shock develop an acute form of remote organ injury of the liver that is both Kupffer cell (KC) and polymorphonuclear (PMN) leukocyte dependent. Circulating plasma xanthine oxidase (XO) has been shown to be responsible for the development of endothelial dysfunction and for remote organ injury of the lung and intestine after ischemia-reperfusion protocols. We now hypothesize that XO is released from rat hind limbs upon reperfusion and that it is responsible for KC and PMN leukocyte activation in this shock model. Our results show that about 30% of rat gastrocnemius muscle xanthine dehydrogenase (XD) is converted to XO during the 5-h tourniquet period and that it is released into the femoral vein within 10 min of reperfusion. Total muscle xanthine oxidoreductase activity (XO + XD) decreases within 30 min of reperfusion and is paralleled by a corresponding increase in femoral vein lactic dehydrogenase. In addition, liver tissue XO increases significantly within 30 min of reperfusion without a corresponding conversion of endogenous XD. Conversion of hepatic XD becomes evident 60 min after reperfusion is initiated, as does XO, and alanine aminotransferase (ALT) release into the hepatic vein, presumably from damaged hepatocytes as a consequence of oxidative stress. Tissue myeloperoxidase activity also increases significantly after the 60-min reperfusion period. That XO mediates KC and PMN activation is supported by the following observations: a) the close relationships between plasma XO and the time courses of tumor necrosis factor-alpha TNFalpha release into the hepatic vein and colloidal carbon clearance by KCs; b) that colloidal carbon clearance, TNFalpha and ALT release, loss of tissue free thiols, lipid peroxidation (TBARS), and liver infiltration by PMN neutrophils can also be induced by the administration of exogenous XO to normal rats; and c) pretreatment of rats with allopurinol inhibits KC activation and liver leukocyte infiltration. These results suggest that XO, released from the ischemic limb on reperfusion, is taken up by the liver were it mediates KC and PMN neutrophil activation and thus contributes to the development of multiple system organ failure after hind limb reperfusion.

Topics: Alanine Transaminase; Animals; Female; Hindlimb; Ischemia; Kupffer Cells; L-Lactate Dehydrogenase; Liver; Macrophage Activation; Muscle, Skeletal; Neutrophils; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion; Shock; Time Factors; Tourniquets; Xanthine Dehydrogenase; Xanthine Oxidase

Applying the orthotopic rat liver transplantation (ORLT) model, postoperative survival has been shown to be mainly dependent on the portal vein clamping time (PVCT). It was hypothesized that prolonged intestinal congestion was responsible for the activation of Kupffer cells (KC) with overproduction of TNF, secondary to splanchnic endotoxin accumulation and release on reperfusion. The role of KCs was directly investigated in the context of long PVCTs by eliminating them (using liposome-encapsulated dichloromethylene diphosphonate), by preventing their activation (using a calcium channel blocker, nisoldipine) and by inhibiting TNF production (using thalidomide). Livers from different groups of rats were transplanted following 24-h cold preservation in the UW solution with long PVCTs (from 18-21 min). KCs depletion, preservation with nisoldipine and pretreatment with thalidomide significantly improved survival in conditions using long PVCTs. KC depletion and nisoldipine preservation had no effect on liver enzymes or pathological findings while lung injury was significantly improved. The present data confirm that, in the context of ORLT with long PVCTs, KCs are directly responsible for the systemic endotoxin-like shock syndrome and their effect is mediated through overproduction of TNF.

Topics: Adenosine; Adenosine-5'-(N-ethylcarboxamide); Allopurinol; Animals; Calcium Channel Blockers; Cell Count; Clodronic Acid; Cold Temperature; Constriction; Glutathione; Graft Survival; Hepatectomy; Immunosuppressive Agents; Insulin; Ischemia; Kupffer Cells; Liposomes; Liver; Liver Transplantation; Lung; Macrophage Activation; Male; Nisoldipine; Organ Preservation Solutions; Portal Vein; Postoperative Complications; Raffinose; Rats; Rats, Inbred Lew; Reactive Oxygen Species; Shock; Thalidomide; Time Factors; Tissue and Organ Procurement; Tumor Necrosis Factor-alpha

This study was designed to determine whether oxygen-derived free radicals play a role in the pathogenesis of gastric mucosal lesions produced by haemorrhagic shock and reperfusion experimental model in the rat. Ranitidine (H2-receptor blocker) in different doses, allopurinol, an inhibitor of xanthine oxidase and SOD (superoxide dysmutase) pre-treatment were used against haemorrhagic shock and reperfusion induced gastric mucosal lesions. Altogether 67 rats were divided into seven different groups. The area of gastric mucosal lesions was measured, the activity of endogenous peroxidase was examined histochemically and histological grading was made. Evans blue was used to demonstrate the improved permeability of gastric mucosal membranes. Ranitidine, in high dose, allopurinol and superoxide dysmutase significantly protected against haemorrhagic shock-induced gastric mucosal lesions, against improved membrane permeability and peroxidation.

Topics: Allopurinol; Animals; Free Radical Scavengers; Free Radicals; Gastric Mucosa; Histamine H2 Antagonists; Histocytochemistry; Male; Peroxidase; Ranitidine; Rats; Rats, Wistar; Reperfusion Injury; Shock; Shock, Hemorrhagic; Superoxide Dismutase; Xanthine Oxidase

Post-ischemic hepatic injury is characterized by zonal heterogeneity of injury (central lobular necrosis), sinusoidal neutrophil accumulation, and injury generated by reactive oxygen metabolites. We evaluated the role of the heterogeneous distribution of hepatic xanthine oxidase in the generation of neutrophil accumulation and consequent hepatocellular injury in rats subjected to shock [controlled hemorrhagic hypotension (mean arterial pressure = 37.5 + or - 2.5 mmHg for 120 min)], with or without subsequent resuscitation and hemodynamic stabilization, compared with sham-operated rats. Shock/resuscitation produced striking neutrophil accumulation (assayed by esterase histochemistry) in the pericentral sinusoids, associated with centrolobular necrosis. This paralleled the pericentral distribution of xanthine oxidase (determined by histochemical assay of frozen sections) and its release from the liver into the circulation at resuscitation. Pretreatment with allopurinol inhibited hepatic xanthine oxidase activity, neutrophil accumulation, and pericentral hepatocyte necrosis in shock/resuscitation in rats. These findings suggest that reactive oxygen metabolites generated by heterogeneously distributed xanthine oxidase may contribute to the heterogeneity of hepatocellular injury in "ischemic hepatitis."

Topics: Animals; Cell Movement; Liver; Male; Necrosis; Neutrophil Activation; Neutrophils; Rats; Rats, Sprague-Dawley; Shock; Xanthine Oxidase

To ascertain whether surgery causes ischaemia-reperfusion (I-R) related injury, if this injury is augmented by preoperative shock, and reduced with low dose allopurinol.. Randomised blind placebo controlled trial.. Surgical laboratory.. 22 pigs were randomly allocated to four groups; OP = operation/placebo, OA = operation/ allopurinol, SOP = shock + operation/placebo, SOA = shock + operation/allopurinol. An aortic tube prosthesis was inserted in all. In groups SOP and SOA preoperative shock was induced by exsanguination. Allopurinol was administered in group OA on the preoperative day and peroperatively, in group SOA during shock and peroperatively.. Perioperative blood concentrations of thiobarbituric acid reactive species (TBARS), ascorbic acid (AA), albumin, 99mTc-albumin and creatine phosphokinase (CPK) as indicators of oxidative membrane damage, antioxidant activity, microvascular permeability changes and muscular cell damage respectively.. In the OP and OA groups TBARS gradually increased, while AA, 99mTc-albumin and CPK remained unchanged and albumin decreased. No effect of allopurinol was observed in these groups. In the SOP group TBARS and AA were not significantly different from groups OP and OA. Yet, albumin, 99mTc-albumin and CPK decreased significantly more in the SOP group. Compared with the SOP group, allopurinol treatment (SOA) produced lower TBARS and higher AA levels, and reduced the effect of shock on albumin, 99mTc-albumin and CPK concentrations.. Aortic surgery causes no I-R related damage. Pre-operative shock produces I-R related damage, which is reduced by allopurinol.

Topics: Allopurinol; Animals; Antioxidants; Aorta, Abdominal; Ascorbic Acid; Blood Vessel Prosthesis; Capillary Permeability; Creatine Kinase; Female; Granulocytes; Ischemia; Muscle, Skeletal; Oxidation-Reduction; Placebos; Random Allocation; Reperfusion Injury; Serum Albumin; Shock; Single-Blind Method; Swine; Technetium; Thiobarbituric Acid Reactive Substances

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

Topics: Animals; Dogs; Myocardial Contraction; Myocardial Reperfusion Injury; Reactive Oxygen Species; Shock; Shock, Hemorrhagic; Splanchnic Circulation; Xanthine; Xanthine Oxidase; Xanthines

Our results suggest that xanthine oxidase (XO) contributes to lung neutrophil sequestration in hypovolemic shock. Catheterized rats subjected to shock by phlebotomy (approximately 30% blood loss) had decreased mean arterial blood pressures (P less than 0.05) and increased (P less than 0.05) lung myeloperoxidase (MPO) activities (indicative of lung neutrophil accumulation) compared with sham-treated normotensive rats. In contrast, rats depleted of lung and plasma XO activity by tungsten diet before phlebotomy had decreased (P less than 0.05) lung MPO activities compared with phlebotomized rats fed regular diets.

Topics: Animals; Cell Movement; Lung; Male; Neutrophils; Peroxidase; Rats; Rats, Inbred Strains; Shock; Tungsten; Xanthine Dehydrogenase; Xanthine Oxidase

A stable in vivo preparation of moderate hypovolemia with prompt volume restoration was produced in anesthetized rats. The microcirculation of the terminal ileum was observed in vivo videomicroscopy, and changes in mean arterial pressure (MAP) as well as arteriolar diameters were recorded after a 30-min period in which the MAP was reduced by 50% by bleeding. Volume was restored with shed blood alone (control); dextran 70 alone (dextran); or dextran + hypertonic (7.5%) saline (dextran + HS). A final group of rats was pretreated with allopurinol 5 mg/kg and then treated identically to the control group to assess the role of the xanthine oxidase system in microcirculation changes following hemorrhage. MAP was restored to normal by return of shed blood in control animals, but inflow arterioles (A1) remained significantly constricted. MAP was significantly higher and A1 arteriolar dilation was observed in the dextran + HS group. Responses in allopurinol-pretreated animals were not different from the responses seen in control animals. We conclude that persistent arteriolar constriction is produced by moderate hypovolemia and this effect is ameliorated by volume restoration with dextran + HS.

Topics: Allopurinol; Animals; Arteries; Arterioles; Blood Pressure; Blood Transfusion, Autologous; Dextrans; Fluid Therapy; Ileum; Male; Microcirculation; Rats; Rats, Inbred Strains; Saline Solution, Hypertonic; Shock; Vasoconstriction

Recent data suggest that oxygen free radicals are implicated in the pathogenesis of ischemic injury. This study evaluates the effects of allopurinol, a xanthine oxidase (XO) inhibitor, on malonaldehyde generation, free sulfhydryl levels, oxygen consumption, and water contents of rat gastrocnemius muscles of female Sprague-Dawley rats subjected to tourniquet shock and after hind-limb reperfusion. Serum lactic dehydrogenase isozyme patterns after ligature release were also examined. Our results show that the four muscle parameters were not altered during 5 hr of ischemia, but that on hind-limb reperfusion, malonaldehyde production, SH levels, O2 consumption, and water contents were significantly altered in the control animals, but not in those pretreated with allopurinol. LDH serum patterns of the untreated animals showed the presence of all five isoforms; these were much less evident in the drug-protected rats. Our data suggest that following ischemia, the affected muscles are unable to recover their normal function when reperfusion is resumed. The subsequent damage is probably due to the generation of cytotoxic superoxide radicals formed during the XO-catalyzed transformation of hypoxanthine to uric acid on tissue reoxygenation. The severity of tissue damage is related to the duration of the ischemic episode possibly due to hypoxanthine accumulation during ischemia.

Topics: Allopurinol; Animals; Female; Hindlimb; Injections, Intraperitoneal; Ischemia; Isoenzymes; L-Lactate Dehydrogenase; Lipid Metabolism; Malondialdehyde; Muscles; Oxygen Consumption; Rats; Rats, Inbred Strains; Shock; Sulfhydryl Compounds; Superoxides; Tourniquets; Water

The pathogenesis of burn shock syndrome involves the production of superoxide radicals which are first generated in the burned skin. They are responsible for an increase in vascular permeability with loss of plasma, which results in hemoconcentration and hypovolemia. The resulting systemic hypoperfusion leads to a generalized production of superoxide radicals and subsequent cellular damage. Prior administration of allopurinol or superoxide dismutase increases the survival rates of mice subjected to burn shock.

Topics: Allopurinol; Animals; Burns; Female; Free Radicals; Hematocrit; Hemodynamics; Mice; Pigmentation; Shock; Superoxide Dismutase; Superoxides; Urinary Bladder

Topics: Allopurinol; Child; Critical Care; Humans; Infusions, Parenteral; Shock

Various metabolic, cellular, and subcellular alterations in cell function and morphology occur during shock or low-flow conditions. In attempting to find treatment programs that would be beneficial following shock, various substrates have been used. Infusion of hypertonic glucose during shock has been shown to improve survival; however, it is unlikely that the effect of glucose is by provision of energy until the circulation is restored. Infusion of glucose--insulin--potassium during shock has also been reported to be beneficial in certain clinical situations. Controversies exist concerning the efficacy of infusions of cyclic AMP, nicotinamide, and Krebs cycle intermediates during shock. Pretreatment of kidneys with inosine or raising glycogen stores of the myocardium have been shown to have protective effects of kidneys and myocardium during ischemia and these procedures may be suitable for organ preservation. Pretreatment with allopurinol has been shown to be beneficial in shock; however, it is unlikely that allopurinol by itself if given following shock would have any salutary effects. Treatment with ATP-MgCl2 has been shown to be beneficial following hemorrhagic shock, sepsis, endotoxin shock, burns, postischemic hepatic failure, and postischemic renal failure. Thus, provision of energy directly in the form of ATP during adverse circulatory conditions appears to be the most advantageous and direct method for the treatment of shock.

Topics: Adenosine; Adenosine Triphosphate; Allopurinol; Animals; Cyclic AMP; Dogs; Glucose; Humans; Inosine; Insulin; Niacinamide; Rabbits; Rats; Shock

Rats were anesthetized and their lift kidneys were made ischemic for 1 h by clamping of the aorta just above the left renal artery. Mannitol (2.5 g/kg), Dextran 70 (0.6 g/kg), methylprednisolone (50 and 100 mg/kg), and allopurinol (100 mg/kg body weight) were administered before, during, or after the ischemia period in order to test the effect of each of these drugs upon this model of renal injury. At 24 h after the release of the aortic clamp the left kidneys of the drug treated animals wwere perfusion fixed and processed for light and electron microscopy. Dextran administration to animals with ischemic kidneys gave rise to a pronounced vacuolization ("osmotic nephrosis"), in the entire proximal tubule and especially in the pars recta. This was in contrast to dextran administration to rats with nonischemic kidenys, which showed no or very mild "osmotic nephrosis." This demonstrates that ischemia makes rat kidneys more susceptible to the development of "osmotic nephrosis." In controls (no drug treatment) one hour of renal ischemia gave partial necrosis of pars recta of the proximal tubule, while the pars convoluta tubule survived. Mannitol treatment significantly reduced the amount of necrosis of the pars recta, whereas dextran, methylprednisolone, and allopurinol had no or a negative effect on the survival of the cells of the pars recta segment. It is suggested that mannitol protects against the development of necrosis by increasing medullary blood flow in combination with a counteractive influence on the cellular swelling, which is known to occur in ischemia.

Topics: Allopurinol; Animals; Dextrans; Ischemia; Kidney Tubules, Proximal; Male; Mannitol; Methylprednisolone; Microscopy, Electron; Necrosis; Rats; Shock

Topics: Adenine Nucleotides; Allopurinol; Animals; Male; Rabbits; Rats; Shock; Shock, Hemorrhagic; Uric Acid

Topics: Acidosis; Allopurinol; Animals; Bicarbonates; Blood Pressure; Carbon Dioxide; Diuresis; Dogs; Female; Hydrogen-Ion Concentration; Male; Partial Pressure; Shock; Time Factors; Tourniquets; Uric Acid; Xanthine Oxidase