The primary localization of free radical generation after anoxia/reoxygenation in isolated endothelial cells

While free radical-mediated reperfusion injury is clearly important in a variety of disparate organs, the particular cellular source of these radicals is unclear. To address this question, we subjected relatively pure (92% +/- 3% by factor VIII immunoassay) cultures of rat pulmonary artery endothelial cells to 0 to 45 minutes of anoxia (95% N2, 5% CO2), followed by reoxygenation (95% air, 5% CO2), to simulate ischemia/reperfusion. Cell injury was assayed after reoxygenation by the release of previously incorporated 51chromium and/or lactate dehydrogenase, and viability was determined by means of trypan blue exclusion. These three end points correlated closely. Without anoxia, the cells remained viable, with minimal evidence of injury for the entire experimental period, while 45 minutes of hypoxia followed by 30 minutes of reoxygenation produced substantial evidence of cell injury in 71% +/- 6% of the cells. This injury was reduced to 21% +/- 2% by treatment with the highly specific free radical scavengers superoxide dismutase and catalase together, either before anoxia or after anoxia, but just before reoxygenation. Similar protection was provided by xanthine oxidase inhibition with allopurinol. The injury was mimicked (without anoxia) by the exogenous generation of superoxide radicals with xanthine and xanthine oxidase. These experiments establish the essential components of free radical generation at reperfusion to be localized within the isolated endothelial cell in the absence of neutrophils or parenchymal cells.     

Pulmonary reperfusion injury: evidence for oxygen-derived free radical mediated damage and effects of different free radical scavengers

Blood granulocyte-mediated reactions involving generation of oxygen-derived free radicals have recently been shown to be capable of causing injury to the lungs. These findings suggest a similar mechanism also to be involved in the development of pulmonary ischemia/reperfusion injury. In the present study, therefore, the effects of three oxygen-derived free radical scavengers, superoxide dismutase (SOD; 1 mg/kg), catalase (20000 IU/kg) and allopurinol (45 mg/kg), were evaluated during reperfusion in a rabbit model after 2 h normothermic ischemia of the lung. During reperfusion, ischemic lungs were found to have an elevated pulmonary vascular resistance, increased total and extravascular lung water content, and decreased arterial oxygen tension (PaO₂) compared to control animals. SOD and catalase, but not allopurinol, were able to reduce pulmonary injury by lowering the pulmonary vascular resistance, but could not prevent pulmonary damage as shown by total lung water (TLW) or PaO₂. It is concluded that oxygen-derived free radicals such as hydrogen peroxide and the superoxide anion may play an important role in precipitating pulmonary injury after ischemia. The failure of xanthine oxidase inhibition (allopurinol) to exert protective effects may suggest that oxygen-derived free radical generation following pulmonary ischemia occurs predominantly via leukocyte-mediated reactions.     

Albumin and Hydroxyethyl Starch Modulate Oxidative Inflammatory Injury to Vascular Endothelium

Background: Human serum albumin is used clinically to maintain colloid osmotic pressure and is viewed to serve an antioxidant role in the vascular compartment via binding of redox-active metal complexes, transport of nitric oxide, and the oxidant-scavenging reactions of the single thiol of human serum albumin, cys34. Because of these potentially desirable adjunctive actions, we evaluated the purity and thiol redox state and compared the relative effects of clinically available 25% human serum albumin preparations with a starch-derived colloid, 6% hydroxyethyl starch, in in vitro models of inflammatory vascular injury.

Methods: Bovine aortic endothelial cell responses to chemical, enzymatic, and cell-derived reactive inflammatory mediators in the presence of human serum albumin or hydroxyethyl starch were assessed.

Results: The cys34 thiol of fresh human serum albumin preparations was 70-85% oxidized and contained a population of human serum albumin (approximately 25% of total) having the cys34 resistant to reduction by 2-mercaptoethanol and NaBH4. Treatment of bovine aortic endothelial cells with human serum albumin dose-dependently protected from HOCl-mediated 14C-adenine release, with this protective effect of human serum albumin not dependent on protein thiol status. Addition of human serum albumin to cell media provided no protection from the cytotoxic actions of peroxynitrite and xanthine oxidase-derived reactive species. Binding of activated polymorphonuclear leukocytes to bovine aortic endothelial cells was significantly amplified by hydroxyethyl starch and inhibited by human serum albumin administration. The binding of neutrophil-derived myeloperoxidase to bovine aortic endothelial cells, a mediator of multiple oxidative and nitric oxide-consuming reactions, was also inhibited by human serum albumin and enhanced by hydroxyethyl starch.     

Albumin and hydroxyethyl starch modulate oxidative inflammatory injury to vascular endothelium

BACKGROUND: Human serum albumin is used clinically to maintain colloid osmotic pressure and is viewed to serve an antioxidant role in the vascular compartment via binding of redox-active metal complexes, transport of nitric oxide, and the oxidant-scavenging reactions of the single thiol of human serum albumin, cys34. Because of these potentially desirable adjunctive actions, we evaluated the purity and thiol redox state and compared the relative effects of clinically available 25% human serum albumin preparations with a starch-derived colloid, 6% hydroxyethyl starch, in in vitro models of inflammatory vascular injury. METHODS: Bovine aortic endothelial cell responses to chemical, enzymatic, and cell-derived reactive inflammatory mediators in the presence of human serum albumin or hydroxyethyl starch were assessed. RESULTS: The cys34 thiol of fresh human serum albumin preparations was 70-85% oxidized and contained a population of human serum albumin (approximately 25% of total) having the cys34 resistant to reduction by 2-mercaptoethanol and NaBH4. Treatment of bovine aortic endothelial cells with human serum albumin dose-dependently protected from HOCl-mediated 14C-adenine release, with this protective effect of human serum albumin not dependent on protein thiol status. Addition of human serum albumin to cell media provided no protection from the cytotoxic actions of peroxynitrite and xanthine oxidase-derived reactive species. Binding of activated polymorphonuclear leukocytes to bovine aortic endothelial cells was significantly amplified by hydroxyethyl starch and inhibited by human serum albumin administration. The binding of neutrophil-derived myeloperoxidase to bovine aortic endothelial cells, a mediator of multiple oxidative and nitric oxide-consuming reactions, was also inhibited by human serum albumin and enhanced by hydroxyethyl starch. CONCLUSIONS: Clinical human serum albumin preparations show modest intrinsic non-thiol-dependent antiinflammatory properties in vitro, a phenomenon that was not observed with hydroxyethyl starch.     

Role of oxygen-derived free radicals in digestive tract diseases

Evidence is presented that supports a role of oxygen free radicals in the pathogenesis of various disorders of the digestive system. In the intestine, there is evidence that oxygen radicals play an important role in the endothelial and epithelial damage associated with certain models of ischemia. The mechanism for superoxide production in this condition differs from that described for other pathologic states (i.e., oxygen toxicity and neutrophil-mediated inflammation). This mechanism involves the reaction of xanthine oxidase, hypoxanthine, and molecular oxygen to produce a burst of oxygen radicals with reperfusion of the ischemic bowel. Evidence implicating oxygen radicals in inflammatory disorders of the digestive tract (i.e., pancreatitis), radiation injury, and hepatic cirrhosis is also presented. The available data suggest that oxygen radicals appear to be a fundamental mechanism of tissue injury in the pathogenesis of various disorders of the digestive system.     

在培养的人胚软骨细胞中硒的抗氧自由基损伤作用观察

目的：观察自由基的对培养的人胚软骨及硒的防护作用。方法：在体外培养的人胚关节软骨细胞培养液中,加入黄嘌呤,黄嘌呤氧化酶及微量元素硒。测定软骨细胞ＤＮＡ和蛋白质及软骨基质中蛋白多糖和胶原的含量要比伸的蠕变量大结果：培养１４４ｈ,软骨细胞ＤＮＡ,蛋白质及软基质中蛋白多糖含量都明显减少,但胶原含量无明显改变,含硒组减少程度轻。结论：自由基可能和退形性关节疾病因有关,是否选择微量硒预防及治疗自由基引起的软     

Minimal role of xanthine oxidase and oxygen free radicals in rat renal tubular reoxygenation injury

The role of xanthine oxidase and oxygen free radicals in postischemic reperfusion injury in the rat kidney remains controversial. Proximal tubules, the focal segment affected by ischemic renal injury, were isolated in bulk, assayed for xanthine oxidase activity, and subjected to 60 min of anoxia or hypoxia and 60 min of reoxygenation to evaluate the participation of xanthine oxidase and oxygen radicals in proximal tubule reoxygenation injury. The total xanthine oxidase in isolated rat proximal tubules was 1.1 mU/mg of protein, approximately 30% to 40% of the activity found in rat intestine and liver. Lactate dehydrogenase release, an indicator of irreversible cell damage, increased substantially during anoxia (39.8 +/- 2.3 versus 9.8 +/- 1.8% in controls) with an additional 8 to 12% release during reoxygenation. Addition of 0.2 mM allopurinol, a potent xanthine oxidase inhibitor, and dimethylthiourea, a hydroxyl radical scavenger, failed to protect against the reoxygenation lactate dehydrogenase release. Analysis of xanthine oxidase substrate levels after anoxia and flux rates during reoxygenation indicates that hypoxanthine and xanthine concentrations are in a 15-fold excess over the enzyme Km and 0.3 mU/mg of protein of xanthine oxidase activity exists during reoxygenation. Hypoxic tubule suspensions had a minimal lactate dehydrogenase release during hypoxia and failed to demonstrate accelerated injury upon reoxygenation. In conclusion, although xanthine oxidase is present and active during reoxygenation in isolated rat proximal tubules, oxygen radicals did not mediate reoxygenation injury.     

Interaction of platelet activating factor, reactive oxygen species generated by xanthine oxidase, and leukocytes in the generation of hepatic injury after shock/resuscitation

OBJECTIVE: To evaluate the putative relation of platelet activating factor (PAF), xanthine oxidase, reactive oxidants, and leukocytes in the pathogenesis of hepatic injury after shock/resuscitation (S/R) in vivo. BACKGROUND: Reactive oxygen metabolites generated by xanthine oxidase at reperfusion have been found to trigger postischemic injury in many organs, including the liver. However, the precise linear sequence of the mechanism of consequent hepatic injury after S/R remains to be characterized. METHODS: Unheparinized male rats were bled to a mean blood pressure of 45 +/- 3 mmHg. After 2 hours of shock, they were resuscitated by reinfusion of shed blood (anticoagulated with citrate-phosphate-dextrose) and crystalloid and observed for the next 6 or 24 hours. RESULTS: S/R caused the oxidation of hepatic glutathione and generated centrolobular leukocyte accumulation at 6 hours, followed by predominantly centrolobular hepatocellular injury at 24 hours. Each of these components was attenuated by PAF inhibition with WEB 2170, xanthine oxidase inhibition with allopurinol, antioxidant treatment with N-acetylcysteine, or severe leukopenia induced by vinblastine. In each case, the degree of leukocyte accumulation at 6 hours correlated with the hepatocellular injury seen at 24 hours. However, xanthine oxidase inhibition with allopurinol failed to attenuate further the small level of residual hepatocellular injury seen in leukopenic rats. CONCLUSION: These findings suggest that reactive oxidants generated by xanthine oxidase at reperfusion, stimulated by PAF, mediate hepatocellular injury by triggering leukocyte accumulation, primarily within the centrolobular sinusoids.     

Free radicals and cardioplegia: allopurinol and oxypurinol reduce myocardial injury following ischemic arrest

Oxygen-derived free radicals generated by xanthine oxidase may represent a major cause of myocardial injury during ischemia and reperfusion. We have used the isolated working rat heart model of cardiopulmonary bypass and ischemic arrest to assess whether allopurinol or oxypurinol, which should prevent free radical formation through their ability to inhibit xanthine oxidase, can improve postischemic myocardial recovery when the drugs are administered either chronically (pretreatment) or acutely (as an addition to the cardioplegic or reperfusion solution). With normothermic ischemic arrest, both drugs, when given either chronically or acutely, significantly improved postischemic recovery of function. However, under hypothermic conditions, allopurinol conferred no protection when given either as pretreatment or during reperfusion, but it was effective when added to the cardioplegic solution. When administered under the appropriate conditions, both allopurinol and oxypurinol enhanced the protective effect afforded by the St. Thomas' Hospital cardioplegic solution, possibly by inhibiting xanthine oxidase activity and preventing the formation of oxygen-derived free radicals.     

Is Ischemic Preconditioning a Useful Strategy in Steatotic Liver Transplantation?

This study examined the effect of preconditioning on steatotic livers for transplantation and attempted to identify the underlying protective mechanisms. Blood flow alterations, neutrophil accumulation, tumor necrosis factor alpha release and lipid peroxidation were observed in nonsteatotic livers after transplantation. Steatotic and nonsteatotic liver grafts were similar in their blood flow, neutrophil accumulation, and TNF release after transplantation. However, in the presence of steatosis, lipid peroxidation and hepatic injury increased. In addition, recipients of steatotic liver grafts were more vulnerable to lung damage associated with transplantation. The conversion of xanthine dehydrogenase to xanthine oxidase and the accumulation of xanthine during cold ischemia was greater in steatotic than in nonsteatotic liver grafts. The results obtained with xanthine oxidase inhibitors indicated that xanthine/xanthine oxidase could be responsible for the increased lipid peroxidation as well as the exacerbated liver and lung damage associated with transplantation of steatotic livers. Preconditioning reduced the xanthine accumulation and percentage of xanthine oxidase seen in steatotic liver grafts during cold ischemia, and conferred protection against liver and lung damage following transplantation. The benefits of preconditioning could be mediated by nitric oxide. These findings suggest that preconditioning could be a relevant new strategy to protect against the inherent risk of steatotic liver failure following transplantation.     

Superoxide production by neutrophils in a model of adult respiratory distress syndrome

Neutrophils (polymorphonuclear leukocytes [PMNs]) are thought to contribute to the pathophysiology of adult respiratory distress syndrome (ARDS) by the release of toxic oxygen metabolites. This study investigated superoxide production by circulating and bronchoalveolar lavage (BAL) PMNs in a rat model of ARDS induced by chronic Escherichia coli (lipopolysaccharide) endotoxemia. Superoxide production was stimulated by fmet-leu-phe, opsonized zymosan, and phorbol myristate acetate. Circulating and BAL PMNs from lipopolysaccharide-infused rats compared with PMNs from control rats are primed for nonselective increased superoxide production. The BAL PMNs are not only partially primed to release superoxide on adherence, they concomitantly have a depressed superoxide response to a phagocytic (opsonized zymosan) stimulus. These PMN responses may partially explain both the pulmonary injury and the increased susceptibility to pulmonary infection seen in patients with ARDS.     

Cardiac ischemic preconditioning improves lung preservation in valve replacement operations

BACKGROUND: Previous work has shown that cardiac ischemic preconditioning reduces cardiac reperfusion injury. We investigated whether cardiac ischemic preconditioning can improve lung preservation in patients who undergo valve replacement. METHODS: Forty patients with rheumatic heart disease requiring valve replacement were randomly divided into two groups. Twenty patients received two cycles of 3 minutes of aortic cross-clamping and 2 minutes of reperfusion before cardioplegic arrest (group IP), and 20 patients underwent 10 minutes of cardiopulmonary bypass (group C, control group). Blood samples from the pulmonary vein were collected to measure levels of polymorphonuclear leukocytes, superoxide dismutase, malonedialdehyde, and thromboxane B2, and arterial oxygen tension. Blood samples from the coronary sinus were used to measure calcitonin gene-related peptide values. Hemodynamic data were recorded by a pulmonary artery Swan-Ganz catheter. Lung tissue was collected after 1 hour of reperfusion to evaluate morphology. Clinical outcome data were recorded. RESULTS: In group C (cardiopulmonary bypass and cardioplegic arrest), the levels of polymorphonuclear leukocytes, thromboxane B2, malonedialdehyde, and calcitonin gene-related peptide were increased after 1 hour of reperfusion, whereas the value for superoxide dismutase was decreased. In group IP, preconditioning attenuated the increase in polymorphonuclear leukocytes, thromboxane B2, and malonedialdehyde (p < 0.05) and increased superoxide dismutase and calcitonin gene-related peptide levels (p < 0.05). Preconditioning also increased arterial oxygen tension and cardiac index compared with controls (p < 0.05) and decreased mean pulmonary artery pressure and pulmonary vascular resistance index (p < 0.05). Histologic findings showed less lung injury and a lower polymorphonuclear leukocyte count in group IP than in group C (p < 0.05). Group IP had fewer postoperative pulmonary complications and a shorter intubation time. CONCLUSIONS: Cardiac ischemic preconditioning improves lung preservation in patients having valve replacement. The mechanism may be that cardiac ischemic preconditioning reduces the accumulation of polymorphonuclear leukocytes in lung tissue and decreases the formation of oxygen free radicals.     

Effect of oxygen free radicals on rabbit and human erythrocytes. Studies on cellular deformability

Changes in deformability of rabbit and human erythrocytes caused by exposure in vitro to the oxygen free radical generator hypoxanthine and xanthine oxidase were studied. The deformability reduction observed after 30 min of exposure to hypoxanthine-xanthine oxidase could be prevented by pretreatment with SOD, while after only 5 min of such exposure allopurinol and catalase also appeared to have a protective effect. Exposure of human erythrocytes to hypoxanthine and xanthine oxidase in Krebs solution prevented an otherwise occurring hemolysis. Exposure to both substances or to xanthine oxidase alone in Dulbeccos phosphate solution produced a reduction in deformability. The results indicate that exposure of erythrocytes to free oxygen radicals reduces deformability and that this effect may contribute to the myocardial dysfunction and the epicardial erythrostasis observed during open-heart surgery.     

Neutropenia prevents decrease in strength of rat intestinal anastomosis: partial effect of oxygen free radical scavengers and allopurinol

A marked decrease in strength, probably due to local collagenolysis, occurs early after surgery in tissues adjacent to an incisional wound. To examine the role of the neutrophils, antineutrophil serum (ANS) was given to rats before and after a standardized end-to-end ileoileal anastomosis. Preimmune serum (PIS) was given to control rats. The decrease in anastomotic breaking strength, amounting to 55% in the PIS group, did not occur in ANS-treated rats, in which there was a decrease by more than 95% in the number of circulating polymorphonuclear cells. The decrease in tissue strength seems to be partly from oxygen free radicals, since the free radical scavengers superoxygen dismutase (SOD) and catalase prevented approximately 50% of the decrease. The xanthine oxidase inhibitor, allopurinol, prevented approximately 30% of the decrease. This is consistent with oxygen free radicals being partly generated by the neutrophils and partly generated after conversion of tissue xanthine dehydrogenase to xanthine oxidase. In contrast to ANS, SOD and catalase were unable to fully prevent the decrease in breaking strength. Therefore some other factor in addition to oxygen free radicals should be involved. One such factor may be the release of collagenolytic proteinases, e.g., elastase and cathepsin G, from the neutrophils.     

Reactive oxygen molecule-mediated injury in endothelial and renal tubular epithelial cells in vitro

To investigate renal tubular epithelial cell injury mediated by reactive oxygen molecules and to explore the relative susceptibility of epithelial cells and endothelial cells to oxidant injury, we determined cell injury in human umbilical vein endothelial cells and in four renal tubular epithelial cell lines including LLC-PK1, MDCK, OK and normal human kidney cortical epithelial cells (NHK-C). Cells were exposed to reactive oxygen molecules including superoxide anion, hydrogen peroxide and hydroxyl radical generated by xanthine oxidase and hypoxanthine. We determined early sublethal injury with efflux of 3H-adenine metabolites and a decline in ATP levels, while late lytic injury and cell detachment were determined by release of 51chromium. When the cells were exposed to 25, 50, and 100 mU/ml xanthine oxidase with 5.0 mM hypoxanthine, ATP levels were significantly lower (P less than 0.001) in LLC-PK1, NHK-C and OK cells compared to MDCK cells while ATP levels were significantly lower (P less than 0.01) in endothelial cells compared to all tubular cell lines. A similar pattern of injury was seen with efflux of 3H-adenine metabolites. When the cells were exposed to 50 mU/ml xanthine oxidase with 5.0 mM hypoxanthine for five hours, total 51chromium release was significantly (P less than 0.001) greater in LLC-PK1, NHK-C and OK cells compared to MDCK cells, while total 51chromium release was significantly (P less than 0.001) greater in endothelial cells compared to all tubular cells. However, lytic injury was the greatest in LLC-PK1 cells and NHK-C cells while cell detachment was the greatest in endothelial cells. MDCK cells were remarkably resistant to oxidant-mediated cell detachment and cell lysis. In addition, we determined ATP levels, 3H-adenine release and 51chromium release in LLC-PK1, NHK-C and endothelial cells in the presence of superoxide dismutase to dismute superoxide anion, catalase to metabolize hydrogen peroxide, DMPO to trap hydroxyl radical and DMTU to scavenge hydrogen peroxide and hydroxyl radical. We found that catalase and DMTU (scavengers of hydrogen peroxide) provided significant protection from ATP depletion, prevented efflux of 3H-adenine metabolites and cell detachment while DMPO (scavenger of hydroxyl radical) prevented lytic injury. In addition, we found that the membrane-permeable iron chelator, phenanthroline, and preincubation with deferoxamine prevented cell detachment and cell lysis, confirming the role of hydroxyl radical in cell injury.(ABSTRACT TRUNCATED AT 400 WORDS)     

Complement and endotoxin-induced lung injury in sheep

Intravenous infusions of endotoxin in sheep cause lung injury characterized by edema due to increased microvascular permeability. Similar increases in pulmonary microvascular permeability are seen in septic patients with the adult respiratory distress syndrome. Since endotoxin-induced lung injury may be mediated by interactions between products of complement activation and polymorphonuclear leukocytes, plasma and lung lymph from six unanesthetized sheep infused with Escherichia coli endotoxin (1.0 micrograms/kg over 30 min) were examined for complement-derived chemotactic activity. By 2-3 hr following infusion of endotoxin, all animals had the increased lung lymph fluid and protein flows characteristic of permeability edema. Preinfusion samples of plasma and lung lymph did not contain chemotactic activity for polymorphonuclear leukocytes. Following infusion of endotoxin, however, significant chemotactic activity was detected in plasma at 0.5-3.5 hr (P less than 0.05) and in lymph at 1.5-6.5 hr (P less than 0.025). The chemotactic activity was heat stable (56 degrees C for 30 min) but was abolished by treatment with antibodies to C5. These data indicate that infusions of endotoxin lead to the generation in plasma, and the appearance in lung lymph, of C5-derived peptides with chemotactic activity for polymorphonuclear leukocytes. C5-derived peptides may account for the pulmonary microvascular leukostasis and endothelial injury that lead to increased permeability edema after infusions of endotoxin.     

Xanthine oxidase in experimental spinal cord injury.

The excessive generation of free radicals is thought to be one of the major mechanisms leading to tissue injury in various pathological conditions, including ischemia, inflammation, and trauma. Conversion of xanthine dehydrogenase (XDH) to xanthine oxidase (XO) contributes to the formation of superoxide, an oxygen radical. We measured XDH and XO activity using a newly developed fluorometric assay in an experimental spinal cord injury model in rats. XO activity increased by more than 100% 4 h after spinal cord trauma. Total (XDH + XO) activity also increased by 96% during the same period. Allopurinol, an inhibitor of XO (100 mg/kg/day x 2 days, i.p.), completely inhibited plasma and spinal cord XO activity but did not affect posttraumatic edema determined by water content or polymorphonuclear (PMN) cell infiltration reflected by myeloperoxidase (MPO) activity in traumatized spinal cord. These results indicate that XDH conversion to XO may not be the major mechanism of oxygen radical formation in the pathogenesis of vasogenic edema or inflammatory response in this experimental spinal cord injury model in rats.     

Xanthine oxidase inhibition attenuates ischemic-reperfusion lung injury

Ischemic-reperfusion lung injury is a factor potentially limiting the usefulness of distant organ procurement for heart-lung transplantation. Toxic oxygen metabolites are considered a major etiologic factor in reperfusion injury. Although oxygen-free radicals may be generated by many mechanisms, we investigated the role of xanthine oxidase in this injury process by using lodoxamide, a xanthine oxidase inhibitor, to inhibit ischemic-reperfusion injury in an isolated rat lung model. Isolated rat lungs were perfused with physiologic salt solution (PSS) osmotically stabilized with Ficoll until circulating blood elements were nondetectable in the pulmonary venous effluent. Lungs were rendered ischemic by interrupting ventilation and perfusion for 2 hr at 37 degrees C. After the ischemic interval, the lungs were reperfused with whole blood and lung injury was determined by measuring the accumulation of 125I-bovine serum albumin in lung parenchyma and alveolar lavage fluid as well as by gravimetric measurements. Lung effluent was collected immediately pre- and postischemia for analysis of uric acid by high-pressure liquid chromatography. Lodoxamide (1 mM) caused significant attenuation of postischemic lung injury. Uric acid levels in the lung effluent confirmed inhibition of xanthine oxidase. Protection from injury was not complete, however, implying that additional mechanisms may contribute to ischemic-reperfusion injury in the lung.     

Allopurinol in Renal Ischemia

ABSTRACT

Allopurinol is a xanthine oxidase inhibitor and antioxidant free radical scavenger which facilitates the protection of ischemic organs in part via this mechanism of action. The accumulation of free radicals during ischemia and reperfusion is in great manner overcome by inhibitors of xanthine oxidase and by the development of endogenous antioxidants. The ischemic lesion generates a well-established inflammatory response with the subsequent production of inflammatory molecules characteristically present at the first stages of the injury. Inflammatory cytokines, chemokines, adhesion molecules, and other cellular and molecular compounds are consequently produced as the lesion sets in. Under these conditions, allopurinol diminishes the effect of inflammatory mediators during the ischemic inflammatory response. This study reviews the literature associated with allopurinol and renal ischemia making special emphasis on the best dose and time of administration of allopurinol regarding its protective effect. It also defines the most accepted mechanism of protection on ischemichally damaged kidneys.     

体外循环中白细胞对肺损伤机制及白细胞过渡的肺保护作用

肺损伤为体外循环术后常见的并发症之一，血液与体外循环管道接触，能够活化补体，激活白细胞，白细胞激活后黏附于血管内皮细胞或进入肺组织，释放具有趋化作用的炎性介质及代谢产物，如蛋白酶，氧自由基和花生四烯酸等在肺损伤中起着重要作用，动物实验及临床应用白细胞过滤器在体外循环中对白细胞进行过滤，肺血管阻力明显降低，血氧饱和度，动脉血氧分压升高，尤其对术前缺氧越重和体外循环时间越长的患者作用越明显，因此，在体外循环中进行白细胞过滤能够减轻其对肺的损伤，起到肺保护作用。