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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pretreatment with a single dose of the oxygen metabolite scavenger 1,3-dimethyl-2-thiourea (DMTU) decreased hyperoxia-induced injury (as assessed by measurement of pleural effusions and increases in hematocrits and blood acid-soluble sulfhydryl levels) in rats that were exposed to hyperoxia for 48 hours. However, the degree of protection was not proportional to DMTU dose. An intermediate dose of DMTU (250 mg/kg) reduced injury more than a lower dose of 125 mg/kg and at least as effectively as the higher, widely used dose of 500 mg/kg DMTU. In contrast to its protective action with respect to hyperoxic injury, none of the doses of DMTU that were tested decreased the elevations in lung oxidized glutathione levels or oxidized glutathione/reduced glutathione ratios associated with hyperoxia exposure. These findings indicate that maximal protection from hyperoxic injury may be achieved with doses of DMTU that are lower than the doses used routinely. The failure of DMTU to decrease lung oxidized glutathione and lung oxidized glutathione/reduced glutathione ratio increases after hyperoxia exposure suggests that the mechanism by which DMTU confers protection requires careful evaluation.
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PMID:Effects of dimethylthiourea in hyperoxic injury. 158 7

Recent work with isolated blood vessels has emphasized the importance of intact endothelium when the relaxation of vascular smooth muscle is induced by acetylcholine (ACh). However, the physiologic significance of this endothelial-dependent ACh response in a complete organ circulation is unclear. We questioned whether diminished ACh vasodilation would result from damage of lung vascular endothelium and whether this response could be used as an indication of endothelial injury. We therefore induced pulmonary endothelial cell injury in one rat model by repeated injections of alpha-naphthyl thiourea (ANTU) and in a second rat model by exposing rats for 52 h to 100% oxygen at a barometric pressure of 760 torr (hyperoxia). Rats injected with Tween 80, the solvent for ANTU, or exposed to ambient Denver air served as the respective control animals. The isolated lungs of these rats were perfused with a recirculating cell- and plasma-free, physiological salt solution to study the effect of ACh or NaCl infusion on pulmonary perfusion pressure and vascular responsiveness. ANTU-treated rats demonstrated an intact vasodilatory response after ACh infusion when compared with the solvent control animals. The immediate pulmonary vasodilation after ACh infusion was slightly enhanced in the hyperoxic rat lung when compared with the rats exposed to ambient air, but there was no difference between these groups in the prolonged depression of vascular responsiveness to hypoxia or angiotensin II. Thus, in both models of lung endothelial cell injury, the pulmonary vascular responses to ACh were intact.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acetylcholine-induced pulmonary vasodilation in lung vascular injury. 300 69

Damage to alveolar macrophages (AM) from hyperoxia (95% O2) is associated with release of factors that recruit and activate neutrophils, but the mechanisms underlying injury to AM from hyperoxia are unknown. We hypothesized that damage to AM from hyperoxia involves generation of highly reactive toxic oxygen derivatives, and we tested this premise by exposing cultured rabbit AM to hyperoxia in the presence of scavengers that inactivate various reactive oxygen species. We found that either dimethyl thiourea, a scavenger of hydroxyl radical, or catalase, a scavenger of H2O2, protected cultured rabbit AM against hyperoxic damage, which suggests that H2O2 or an H2O2-derived product, such as hydroxyl radical, contribute to damage to AM from hyperoxia.
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PMID:Oxygen radical scavengers protect alveolar macrophages from hyperoxic injury in vitro. 641 52

We tested the hypothesis that hyperoxia does not cause adequate constriction of choroidal vessels of the newborn (1 to 5 days old) pig, resulting in increased O2 delivery to the retina, possibly due to excess production and/or effects of vasodilators such as nitric oxide (NO). Hyperoxia (100% O2, 45 minutes) led to a decrease in retinal blood flow (RBF) of both newborn and juvenile (5 to 6 weeks old) pigs and also reduced choroidal blood flow (ChBF) in juvenile but not in newborn pigs; the absence of hyperoxia-induced ChBF response in the newborn was associated with a rise in choroidal O2 delivery. Ibuprofen (prostaglandin G/H synthase inhibitor) and 1,3-dimethyl-2-thiourea (a free radical scavenger) did not modify the choroidal hemodynamic responses to hyperoxia in newborn pigs. However, in newborn animals treated with the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME), hyperoxia caused a decrease in blood flow and O2 delivery to the choroid. Consistent with these effects of L-NAME, hyperoxia induced an increase in choroidal cGMP in newborn pigs ventilated with 100% O2 and stimulated nitrite production in isolated choroids exposed to hyperoxia from newborn but not juvenile pigs; these effects were inhibited by NOS blockers. Also, both constitutive and inducible NOS activities were higher in choroidal tissues from newborn than from juvenile animals. In addition, the vasorelaxant effect of the NO donor sodium nitroprusside in vitro was also greater on choroids from newborn than from juvenile pigs. Finally, L-NAME prevented the hyperoxia-induced increase in peroxidation products in the choroid of newborns. It is concluded that hyperoxia does not lead to a decrease in blood flow and O2 delivery to the choroid of the newborn because of increased NO synthesis and effects; since the choroid is the main source of O2 supply to the retina, the present data contribute in providing an explanation for the increased susceptibility of the immature neonate to hyperoxia-induced retinopathy.
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PMID:Increased nitric oxide synthesis and action preclude choroidal vasoconstriction to hyperoxia in newborn pigs. 878 83

Pulmonary oedema results from an imbalance between the forces driving fluid into the airspace and the biological mechanisms for its removal. In mice lacking the alpha-subunit of the amiloride-sensitive sodium channel (alphaENaC(-/-)), impaired sodium transport-mediated lung liquid clearance at birth results in neonatal death. Transgenic expression of alphaENaC driven by a cytomegalovirus (CMV) promoter (alphaENaC(-/-)Tg+) rescues the lethal pulmonary phenotype, but only partially restores respiratory sodium transport in vitro. To test whether this may also be true in vivo, and to assess the functional consequences of this defect on experimental pulmonary oedema, we measured respiratory transepithelial potential difference (PD) and alveolar fluid clearance (AFC), and quantified pulmonary oedema during experimental acute lung injury in these mice. Both respiratory PD and AFC were roughly 50% lower (P < 0.01) in alphaENaC(-/-)Tg+ than in control mice. This impairment was associated with a significantly larger increase of the wet/dry lung weight ratio in alphaENaC(-/-)Tg+ than in control mice, both after exposure to hyperoxia and thiourea. Moreover, the rate of resolution of thiourea-induced pulmonary oedema was more than three times slower (P < 0.001) in alphaENaC(-/-)Tg+ mice. alphaENaC(-/-)Tg+ mice represent the first model of a constitutively impaired respiratory transepithelial sodium transport, and provide direct evidence that this impairment facilitates pulmonary oedema in conscious freely moving animals. These data in mice strengthen indirect evidence provided by clinical studies, suggesting that defective respiratory transepithelial sodium transport may also facilitate pulmonary oedema in humans.
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PMID:Defective respiratory amiloride-sensitive sodium transport predisposes to pulmonary oedema and delays its resolution in mice. 1530 80

Receptor for advanced glycation end-products (RAGE) is a marker of alveolar type I cells and is elevated in the pulmonary edema fluid of patients with acute lung injury (ALI). We tested the hypothesis that RAGE in the bronchoalveolar lavage (BAL) would be elevated in experimental models of direct ALI characterized by alveolar epithelial cell injury. We developed ELISA measurements for RAGE and studied ALI (direct and indirect) mouse models and collected BAL at specified endpoints to measure RAGE. We also tested whether levels of BAL RAGE correlated 1) with the severity of lung injury in acid and hyperoxia-induced ALI and 2) with the beneficial effect of a novel treatment, mesenchymal stem cells (MSC), in LPS-induced ALI. In ALI models of direct lung injury induced by intratracheal instillation of acid, LPS, or Escherichia coli, the BAL RAGE was 58-, 22-, and 13-fold elevated, respectively. In contrast, BAL RAGE was not detectable in indirect models of ALI induced by an intraperitoneal injection of thiourea or by an intravenous injection of MHC I monoclonal antibody that produces a mouse model of transfusion-related ALI. BAL RAGE did correlate with the severity of lung injury in acid and hyperoxia-induced ALI. In addition, with LPS-induced ALI, BAL RAGE was markedly reduced with MSC treatment. In summary, BAL RAGE is an indicator of ALI, and it may be useful in distinguishing direct from indirect models of ALI as well as assessing the response to specific therapies.
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PMID:Receptor for advanced glycation end-products (RAGE) is an indicator of direct lung injury in models of experimental lung injury. 1941 9