title: High-altitude pulmonary edema can be prevented by heat shock protein 70-mediated hyperbaric oxygen preconditioning.
abstract: BACKGROUND
  The primary goal of this study was to test whether high-altitude exposure (HAE of 9.7% O2 at 0.47 absolute atmosphere [ATA] for 3 days) was capable of increasing lung edema, neutrophil, and hemorrhage scores as well as decreasing lung levels of both aquaporin 1 (AQP1) and AQP5 proteins and messenger RNA (mRNA) expression in rats, with a secondary goal to test whether a preinduction of heat shock protein 70 (HSP70) by hyperbaric oxygen preconditioning (HBO2P of 100% O2 at 2.0 ATA for 1 hour per day for 5 consecutive days) attenuated the HAE-induced increased lung injury scores and decreased lung AQP1 and AQP5 protein and mRNA expressions.
  
  
  METHODS
  Rats were assigned to (1) non-HBO2P (21% O2 at 1.0 ATA) + non-HAE (21% O2 at 1.0 ATA) group; (2) non-HBO2P + HAE group; (3) HBO2P + HAE group; and HBO2P + HSP70 antibodies (Ab) + HAE group. For the HSP70 Ab group, a neutralizing HSP70 Ab was injected intravenously at 24 hours before HAE. All the physiologic and biochemical parameters were obtained at the end of HAE or the equivalent period of non-HAE. The cardiovascular and blood gas parameters were monitored for all experiments. Bronchoalveolar lavage (BAL) was performed to determine proinflammatory cytokines (interleukin 6, interleukin 1β, and tumor necrosis factor α). Parts of the lung were excised for myeloperoxidase activity measurement, whereas the rest was collected for lung damage score assessments. AQP1 and AQP5 protein and mRAN expressions were also determined in the lung tissues.
  
  
  RESULTS
  In the non-HBO2P + HAE group, the animals displayed higher values of lung myeloperoxidase activity, BAL proinflammatory cytokines, lung water weight, and acute lung injury scores compared with those of the non-HBO2P + non-HAE controls. In contrast, the non-HBO2P + HAE group rats had lower values of lung AQP1 and AQP5 protein and mRNA expressions, mean arterial pressure, heart rate, SO2, Paco2, HCO3, and pH compared with those of non-HBO2P + non-HAE group rats. The increased acute lung edema, neutrophil, and hemorrhage scores; increased BAL levels of proinflammatory cytokines; decreased lung AQP1 and AQP5 protein and mRNA expressions; and hypotension, bradycardia, hypoxia, and acidosis caused by HAE were all significantly attenuated by HBO2P.
  
  
  CONCLUSIONS
  Our data indicate that HBO2P may attenuate high-altitude acute lung injury by a preinduction of lung HSP70 in rats.
authors.affiliation: From the Institute of Medicine and School of Medicine (M.-C.T.), Chung Shan Medical University; and Division of Thoracic Medicine (T.C.-Y.T.), Chung Shan Medical University Hospital and Chung Shan Medical University, Taichung; and Departments of Emergency Medicine (H.-J.L.), Medical Research (M.-T.L.), and Hyperbaric Oxygen (K.-C.N.), Chi Mei Medical Center; and Department of Biotechnology (M.-T.L., C.-P.C.), Southern Taiwan University of Science and Technology, Tainan, Taiwan.
authors.forename: Ming-Che
authors.initials: MC
authors.lastname: Tsai
authors.forename: Hung-Jung
authors.initials: HJ
authors.lastname: Lin
authors.forename: Mao-Tsun
authors.initials: MT
authors.lastname: Lin
authors.forename: Ko-Chi
authors.initials: KC
authors.lastname: Niu
authors.forename: Ching-Ping
authors.initials: CP
authors.lastname: Chang
authors.forename: Thomas Chang-Yao
authors.initials: TC
authors.lastname: Tsao
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism*; D000531:Altitude; D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism; D051402:Aquaporin 5 / Q000378:metabolism; D015153:Blotting, Western; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006931:Hyperbaric Oxygenation; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D011654:Pulmonary Edema / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D051402:Aquaporin 5; D018840:HSP70 Heat-Shock Proteins; D051398:Aquaporin 1