title: Similar but not the same: normobaric and hyperbaric pulmonary oxygen toxicity, the role of nitric oxide.
abstract: Pulmonary manifestations of oxygen toxicity were studied and quantified in rats breathing >98% O(2) at 1, 1.5, 2, 2.5, and 3 ATA to test our hypothesis that different patterns of pulmonary injury would emerge, reflecting a role for central nervous system (CNS) excitation by hyperbaric oxygen. At 1.5 atmosphere absolute (ATA) and below, the well-recognized pattern of diffuse pulmonary damage developed slowly with an extensive inflammatory response and destruction of the alveolar-capillary barrier leading to edema, impaired gas exchange, respiratory failure, and death; the severity of these effects increased with time over the 56-h period of observation. At higher inspired O(2) pressures, 2-3 ATA, pulmonary injury was greatly accelerated but less inflammatory in character, and events in the brain were a prelude to a distinct lung pathology. The CNS-mediated component of this lung injury could be attenuated by selective inhibition of neuronal nitric oxide synthase (nNOS) or by unilateral transection of the vagus nerve. We propose that extrapulmonary, neurogenic events predominate in the pathogenesis of acute pulmonary oxygen toxicity in hyperbaric oxygenation, as nNOS activity drives lung injury by modulating the output of central autonomic pathways.
authors.affiliation: Center for Hyperbaric Medicine and Environmental Physiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Ivan T
authors.initials: IT
authors.lastname: Demchenko
authors.forename: Karen E
authors.initials: KE
authors.lastname: Welty-Wolf
authors.forename: Barry W
authors.initials: BW
authors.lastname: Allen
authors.forename: Claude A
authors.initials: CA
authors.lastname: Piantadosi
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001784:Blood Gas Analysis; D001826:Body Fluids / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018496:Hyperoxia / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008171:Lung Diseases / Q000473:pathology; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000378:metabolism; D010100:Oxygen / Q000633:toxicity*; D011014:Pneumonia / Q000473:pathology; D011654:Pulmonary Edema / Q000097:blood / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014628:Vagotomy
chemical_list: D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D010100:Oxygen