allopurinol and Multiple-Organ-Failure

During liver transplantation, graft ischemia-reperfusion injury leads to a systemic inflammatory response producing postoperative organ dysfunctions. The aim of this observational and prospective study was to compare the impact of Solution de conservation des organes et tissus (SCOT) 15 and University of Wisconsin (UW) preservation solutions on early cytokine release, postreperfusion syndrome and postoperative organ dysfunctions.. Thirty-seven liver transplantations were included: 21 in UW Group and 16 in SCOT 15 group. Five cytokines were measured in systemic blood after anesthetic induction, 30minutes after unclamping portal vein and on postoperative day 1.. Following unclamping portal vein, cytokines were released in systemic circulation. Systemic cytokine concentrations were higher in UW than in SCOT 15 group: Interleukin-10, Interleukine-6. In SCOT 15 group, significant reduction of postreperfusion syndrome incidence and acute kidney injury were observed. Alanine and aspartate aminotransferase peak concentrations were higher in SCOT 15 group than in UW group. However, from postoperative day 1 to day 10, aminotransferase returned to normal values and did not differ between groups.. Compared to UW, SCOT 15 decreases systemic cytokine release resulting from graft ischemia-reperfusion injury and reduces incidence of postreperfusion syndrome and postoperative renal failure.

Topics: Adenosine; Allopurinol; Cytokines; Female; Glutathione; Humans; Insulin; Liver Transplantation; Male; Middle Aged; Multiple Organ Failure; Organ Preservation Solutions; Postoperative Complications; Prospective Studies; Raffinose; Reperfusion Injury; Time Factors

Toxic epidermal necrolysis (TEN) is characterized by fever, scalded appearance of the skin, and epidermolysis associated to blister formation and exfoliation, and it is caused by hypersensitivity reaction to a drug. The authors report two cases of death as a result of TEN; both referred to old aged women treated with a polytherapy including allopurinol. Both patients displayed erythematous skin lesions similar to scald burns and epidermolysis at the face, chest, and abdomen and died shortly after hospitalization. Autopsy findings and histological examinations revealed epidermal necrolysis and confirmed the clinical diagnosis. A strict time-correlation between allopurinol administration and symptoms was evidenced. Because of its iatrogenic origin, TEN often arises suspicions of medical liability; however, because of its unpredictable nature, the occurrence of this syndrome cannot be ascribed to the medical staff whose main task is the rapid diagnosis and the correct management.

Topics: Aged; Allopurinol; Fatal Outcome; Female; Gout Suppressants; Humans; Multiple Organ Failure; Stevens-Johnson Syndrome

The present report describes the case of a 67-year-old patient who developed an allopurinol-induced hypersensitivity syndrome (AHS) with toxic epidermal necrolysis and subsequently died of septic multiorgan failure. Considering the increasing prescription rate of allopurinol, the present case report intends to demonstrate the underestimated threat of AHS.

Topics: Aged; Allopurinol; Diagnosis, Differential; Drug Hypersensitivity; Fatal Outcome; Gout; Humans; Kidney Failure, Chronic; Male; Multiple Organ Failure; Recurrence; Stevens-Johnson Syndrome

Langerhans cell histiocytosis (LCH) is an enigmatic disease usually occurring in children. Tumor lysis syndrome (TLS) is a clinical syndrome associated with severe metabolic derangement and oliguric acute renal failure. In this report, we present the clinical course of an infant with advanced LCH who had TLS develop after chemotherapy. Treatment with continuous arteriovenous hemofiltration resulted in effective control of serum uric acid, potassium, creatinine, phosphorus, and blood urea nitrogen levels in the blood.

Topics: Acute Kidney Injury; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Blood Transfusion; Combined Modality Therapy; Disease Progression; Etoposide; Fatal Outcome; Female; Fluid Therapy; Hemofiltration; Histiocytosis, Langerhans-Cell; Humans; Infant; L-Lactate Dehydrogenase; Lymph Nodes; Mercaptopurine; Multiple Organ Failure; Neck; Orbital Diseases; Prednisolone; Sodium Bicarbonate; Temporal Bone; Tumor Lysis Syndrome; Uric Acid; Vinblastine; Vincristine

The possible role of xanthine oxidase (XO) activation in the signal transduction process during the septic shock syndrome was examined. The XO activity index after caffeine intake was assessed simultaneously with the blood glutathione redox ratio, a known parameter of oxidative stress.. An investigational clinical study in a nine-bed pediatric intensive care unit.. Critically ill infants and children (n = 34) with systemic inflammatory response syndrome following infection, trauma or major surgery. Biochemical investigations (n = 54) were performed at various stages of the shock syndrome, characterized by pediatric risk of mortality and organ dysmetabolic scores. Controls consisted of 30 healthy children.. The in vivo XO activity index was measured as the urinary ratio of two metabolites of caffeine: 1-methyluric acid and 1-methylxanthine. The blood concentrations of oxidized (GSSG) and reduced glutathione (GSH) were determined. The XO activity index and redox ratio GSSG/GSH were highly increased in patients in shock dominated by the clinical symptoms of a proinflammatory response. A significantly lower XO activity index was found with an increased GSSG/ GSH in patients whose stage of shock was characteristic of an excessive anti-inflammatory response. The XO activity index and GSSG/ GSH were correlated closely with each other (r = 0.624, n = 54; p < 0.001), and were also related to the daily severity scores.. Potent and simultaneous activation of the two redox systems strongly indicates a definite role of free radicals from XO in the overspill of the acute proinflammatory reaction of the shock syndrome, followed by a significant downregulation.

Topics: Biomarkers; Case-Control Studies; Child; Child, Preschool; Female; Glutathione; Humans; Infant; Male; Multiple Organ Failure; Oxidation-Reduction; Oxidative Stress; Statistics, Nonparametric; Systemic Inflammatory Response Syndrome; Xanthine Oxidase

Our recent results indicate that pancreatic enzymes in the ischemic intestine are involved in the production of in vivo activators, which stimulate cells in the cardiovascular system and initiate multiple organ failure. Since the intestine is a rich source of xanthine oxidase (XO), we investigated whether XO may be involved in the production of circulating activators in shock. The small intestine was perfused with saline (SAL group), a broad acting pancreatic enzyme inhibitor, ANGD (ANGD group), allopurinol (ALLOP group), or a combination of ANGD and allopurinol (ANGD + ALLOP group). 100 min of splanchnic arterial occlusion was followed by 120 min of reperfusion. Leukocytes from asymptomatic volunteers were incubated with plasma from experimental animals, and the fractions of pseudopod positive cells were counted as an indicator for the activator. ANGD served to preserve the arterial blood pressure (MAP) close to its control values (96.6 +/- 6.2 % in ANGD versus 60.9 +/- 6.2 % in SAL, 120 min after reperfusion, P < 0.05). In line with our previous experiments, ANGD decreased the formation of activator (30.5 +/- 4.8% in SAL versus 7.3 +/- 1.6 % in ANGD, 120 min after reperfusion, P< 0.05). Although allopurinol inhibited the XO in the small intestine, no protection from early indicators of multi-organ injury was detected. The recovery of MAP and reduced levels of plasma activator achieved in the ANGD + ANGD group was similar to those in the ALLOP group. These results indicate that XO may not serve as a significant source for plasma derived activators in an acute phase of shock after severe intestinal ischemia.

Topics: Allopurinol; Animals; Benzamidines; Bile; Blood Pressure; Duodenum; Guanidines; Intestinal Mucosa; Ischemia; Leukocytes; Male; Multiple Organ Failure; Neutrophils; Protease Inhibitors; Rats; Rats, Wistar; Xanthine Dehydrogenase; Xanthine Oxidase

Topics: Acetylcysteine; Adenosine Triphosphate; Allopurinol; Animals; Glutathione; Heart; Intestine, Small; Ischemia; Liver; Lung; Malondialdehyde; Mesenteric Arteries; Multiple Organ Failure; Myocardium; Oxidative Stress; Peroxidase; Rats; Rats, Wistar; Reperfusion Injury; Somatostatin

Cardiovascular, respiratory, and vascular dysfunction can follow trauma-induced no-flow-reflow states: hemorrhage, blunt trauma, or neurogenic shock. Liver ischemia-reperfusion (IR) induces remote lung damage by means of xanthine oxidase (XO) pro-oxidant activity. This damage was not proven in the heart, neither was the independent role of radical oxygen species (ROS) established in such cases. We investigated whether multiple organ dysfunction after a trauma-like IR is XO and ROS related and whether clinically used ROS scavengers could be beneficial.. A controlled, randomized trial in which isolated rat livers, hearts, lungs, and aortic rings were perfused with Krebs-Henseleit solutions. After stabilization, livers were either perfused or made ischemic (2 hours). Then, pairs of liver plus heart, lung, or ring were reperfused in series (15 minutes), and then the second organ circulated alone for 45 minutes. Remote organ protection against the pro-oxidant hepatic-induced toxicity was evaluated by using allopurinol (1 mmol/L, heart), mannitol (0.25 g/kg, lung), or methylene blue (40 mg/kg, ring).. IR liver effluents typically contained high lactate dehydrogenase, XO, and uric acid concentrations compared with control organs. IR was associated with doubled lung peak inspiratory pressure and reduced static compliance. Myocardial velocity of contraction and relaxation decreased by one third of baseline, and rings contracted abnormally and responded inadequately to phenylephrine. Wet-weight to dry-weight ratios in the remote organs increased as well. Most remote reperfusion injuries were attenuated by the drugs.. Liver no-flow-reflow directly induces myocardial, pulmonary, and vascular dysfunction. These are likely mediated by XO and ROS. The tested drugs protected against these pro-oxidants, even in the presence of circulating XO.

Topics: Allopurinol; Animals; Aorta; Coronary Vessels; Disease Models, Animal; Drug Evaluation, Preclinical; Free Radical Scavengers; Heart Arrest; In Vitro Techniques; Liver; Lung; Male; Mannitol; Methylene Blue; Multiple Organ Failure; Multiple Trauma; Myocardium; Random Allocation; Rats; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury; Xanthine Oxidase

In the present study we evaluate the possibility that xanthine oxidase released by damaged pancreas could act as a source of oxidative damage in systemic tissues during the early stages of acute pancreatitis. This was accomplished by evaluating the effects of xanthine oxidase inhibition with oxypurinol infused into the portal vein. Under these conditions, we inhibited the enzyme before it reached the liver and other distant organs, without inducing changes in the severity of pancreatic damage. Results indicate that pancreatitis parallels increases in xanthine oxidase activity in plasma. Superoxide radicals generated by this enzyme appears to be involved in the decrease of reduced glutathione levels in the plasma and liver. In addition, xanthine oxidase inhibition prevents the infiltration of neutrophils into the lungs. We conclude that oxygen free radicals generated by xanthine and xanthine oxidase released to the bloodstream are involved in the systemic organ failure associated with acute pancreatitis.

Topics: Acute Disease; Analysis of Variance; Animals; Disease Models, Animal; Free Radicals; Lipid Peroxidation; Liver; Male; Multiple Organ Failure; Oxidative Stress; Pancreas; Pancreatitis; Rats; Rats, Wistar; Time Factors; Xanthine; Xanthine Oxidase

We hypothesized that multiple organ injury and concentrations of xanthine oxidase (an oxidant-generating enzyme released after hepatoenteric ischemia) would be decreased by the administration of a bolus of a colloid solution at reperfusion.. Randomized, masked, controlled animal study.. University-based animal research facility.. Fifty-four New Zealand white male rabbits, weighing 2 to 3 kg.. Anesthetized rabbits were assigned to either the hepatoenteric ischemia-reperfusion group (n = 27) or the sham-operated group (n = 27). Hepatoenteric ischemia was maintained for 40 mins with a balloon catheter in the thoracic aorta, followed by 3 hrs of reperfusion. Each group was randomly administered a bolus of one of three fluids at the beginning of reperfusion: Hextend (hetastarch solution); 5% human albumin; or lactated Ringer's solution. The investigators were masked as to the identity of the fluid administered.. Multiple organ injury was assessed by the release of lactate dehydrogenase activity into the plasma and by indices of gastric and pulmonary injury. Circulating lactate dehydrogenase activity was significantly greater (p < .001) in animals receiving lactated Ringer's solution than in rabbits receiving either colloid solution. Gastric injury (tissue edema, Histologic injury Score) was significantly decreased (p < .01) by administration of both colloid solutions. Lung injury (bronchoalveolar lavage lactate dehydrogenase activity) was significantly decreased (p < .05) by the hetastarch solution administration. The hetastarch solution administration resulted in 50% less xanthine oxidase activity release during reperfusion compared with albumin or lactated Ringer's solution administration (p < .001).. We conclude that multiple organ injury and xanthine oxidase release after hepatoenteric ischemia-reperfusion are decreased by colloid administration.

Topics: Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Hydroxyethyl Starch Derivatives; Intestines; L-Lactate Dehydrogenase; Liver; Male; Multiple Organ Failure; Plasma Substitutes; Rabbits; Random Allocation; Reperfusion Injury; Xanthine Oxidase

To determine xanthine oxidase activity, free radical concentrations, and lipid peroxidation in patients with sepsis syndrome compared with noninfected critically ill patients.. A prospective observational study.. A nine-bed intensive care unit in a university teaching hospital trust.. Fourteen consecutive patients who met the established criteria for sepsis syndrome with multiple organ dysfunction syndrome, and ten noninfected critically ill patients were studied.. None.. Xanthine oxidase activity was increased in septic patients compared with both healthy volunteers (p < .01) and noninfected patients (p < .05), and was highest in the six patients who survived (p < .05). Lipid peroxides were increased in both septic patients (p < .001) and nonseptic controls (p < .001). Xanthine oxidase activity did not relate to the Acute Physiology and Chronic Health Evaluation (APACHE) II score or to the presence of organ dysfunction. The mean ascorbyl radical concentration (arbitrary units) determined by electron paramagnetic resonance following spin trapping was increased in patients compared with healthy subjects (p < .05).. Patients with sepsis have xanthine oxidase activation, high free-radical concentrations, and evidence of free radical damage. The finding that xanthine oxidase activity was lower in those patients who died, coupled with increased lactate concentrations implies more severe ischemia with incomplete reperfusion resulting in less xanthine oxidase "wash out" into the circulation. Increased ascorbyl radical concentrations may be due to an increased radical generation and oxidant scavenging, but appears to be unrelated to xanthine oxidase activity within the circulation.

Topics: Adult; Aged; Aged, 80 and over; APACHE; Critical Illness; Female; Free Radicals; Humans; Lactates; Lipid Peroxidation; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Survival Rate; Systemic Inflammatory Response Syndrome; Xanthine Oxidase

Endotoxin (lipopolysaccharide) stimulation of macrophages (M phi) induces the generation of toxic reactive oxygen intermediates (ROI); however, recent studies implicate intracellular redox changes in signal transduction pathways for cytokines. To test whether oxidant stress modulates M phi activation, rabbit alveolar M phi were exposed to the following: diamide (oxidizes intracellular glutathione); glucose oxidase (generates hydrogen peroxide); or xanthine oxidase (generates superoxide), before lipopolysaccharide. Supernatants were assayed for tumor necrosis factor (TNF) and cell lysates were assayed for procoagulant activity (PCA). TNF mRNA was analyzed by Northern blot. M phi exposure to diamide and glucose oxidase augmented TNF production, PCA expression, and TNF mRNA accumulation; however, xanthine oxidase exposure inhibited TNF production while augmenting PCA expression. M phi signal transduction can be enhanced by increasing cellular oxidant stress. The differential response of TNF versus PCA suggests the existence of distinct redox-sensitive signal transduction pathways. These data define a mechanism by which oxidants generated during inflammation may modulate M phi function.

Topics: Animals; Blood Coagulation Factors; Cells, Cultured; CHO Cells; Cricetinae; Dactinomycin; Diamide; Electrophoresis; Endotoxins; Glucose Oxidase; Glutathione; Humans; Infant, Newborn; Macrophages, Alveolar; Male; Multiple Organ Failure; NF-kappa B; Oxidants; Oxidation-Reduction; Oxidative Stress; Protein Synthesis Inhibitors; Rabbits; Reactive Oxygen Species; Respiratory Distress Syndrome, Newborn; RNA, Messenger; Superoxides; Tumor Necrosis Factor-alpha; Xanthine Oxidase

Topics: Allopurinol; Chemical and Drug Induced Liver Injury; Fatal Outcome; Gout; Humans; Male; Middle Aged; Multiple Organ Failure

This paper presents a primary study of the treatment of experimental multiple system organ failure (MSOF) in rats. The rats were pretreated with xanthine oxidase inhibitor allopurinol, the energy metabolism regulator fructose-1,6-diphosphate (FDP) and purified Chinese herbal medicine polydatin. The incidence of MSOF decreased from 71.4% in the untreated group to 35.7%, 47.1% and 16.7% in treated groups, respectively, while the mean survival time was prolonged to 38.5h, 30.2h and 41.7h in treated groups, respectively, as compared with 26.4h in the untreated group. In addition to the known antioxidant effect of the allopurinol, this study also suggests that FDP and polydatin enhance the capacity of antioxidtion.

Topics: Allopurinol; Animals; Antioxidants; Free Radicals; Fructose-Bisphosphatase; Glucosides; Glutathione Peroxidase; Male; Malondialdehyde; Multiple Organ Failure; Oxygen; Rats; Rats, Inbred Strains; Stilbenes; Superoxide Dismutase

51 burned patients with TBSA over 30% were studied prospectively. MOF developed in 17 of them. Postburn MOF occurred mainly in those with TBSA over 70%. Mortality of MOF was directly proportional to the number of organs involved. The incidence of pulmonary failure was the highest, and the highest mortality was attributed to renal failure. MOF occurring in the early stage was more related to burn shock, and those occurring in the late stage was predisposed mainly by infection. Oxygen free radicals play an important role in the genesis and development of postburn MOF. In this study, it was revealed that antiperoxidation ability declined, active oxygen was increased, and lipid peroxidation became excessive after the burn injury. It was also found that oxygen free radical-mediated effects produced more serious damages in patients with MOF than those without, and also more in those died than the survivors. The hypoxanthine-xanthine oxidase system was a significant source of oxygen radicals after the burn injury. There were also significant changes in plasma TXA2 and PGI2 levels postburn. The marked increase in TXA2/PGI2 ratio indicated imbalance between TXA2 and PGI2, which was correlated well with burn size and closely related to the development of postburn MOF. The excessive production of TXA2 might trigger or accelerate the formation of microaggregates and thromboxane, subsequently leading to visceral damages and failure.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Burns; Female; Humans; Male; Malondialdehyde; Multiple Organ Failure; Shock, Traumatic; Superoxide Dismutase; Thromboxane B2; Xanthine Oxidase

We have previously shown that gut ischemia/reperfusion (I/R) causes simultaneous liver and lung dysfunction and that neutrophils play a critical role in this process. The purpose of this study was to ascertain whether xanthine oxidase (XO) was likewise operational. Normal and XO-inactivated rats (given a tungsten-enriched, molybdenum-depleted diet for 3 weeks) underwent 45 minutes of occlusion of the superior mesenteric artery, and control rats were subjected to a sham laparotomy. After zero and six hours of reperfusion, blood was sampled and livers and lungs harvested. Iodine-125-labeled albumin leak was used as a marker for pulmonary and liver capillary permeability barrier function, and serum acetoacetate/3-hydroxybutyrate (AcAc/3-OHB) levels as an index of hepatic mitochondrial redox state. Gut ischemia/six hours of reperfusion (I/R) increased the 125I albumin lung/blood ratio and the 125I albumin liver/blood ratio; AcAc/3-OHB levels decreased significantly. Xanthine oxidase activation eliminated the observed lung and liver capillary leak as well as the hepatic metabolic derangement induced by gut I/R. In conclusion, the simultaneous lung and liver dysfunction produced by gut I/R is mediated by XO.

Topics: Animals; Disease Models, Animal; Evaluation Studies as Topic; Ischemia; Liver; Lung; Male; Mesentery; Multiple Organ Failure; Neutrophils; Rats; Rats, Inbred Strains; Reperfusion Injury; Respiratory Distress Syndrome; Serum Albumin, Radio-Iodinated; Xanthine Oxidase