title: Physiological effects of oxidized exogenous surfactant in vivo: effects of high tidal volume and surfactant protein A.
abstract: Oxidative damage to surfactant can decrease lung function in vivo. In the current study, our two objectives were: 1) to examine whether the adverse effects of oxidized surfactant would be accentuated in animals exposed to high tidal volume ventilation, and 2) to test whether supplementation with surfactant protein A (SP-A) could improve the function of oxidized surfactant in vivo. The first objective was addressed by evaluating the response of surfactant-deficient rats administered normal or oxidized surfactant and then subjected to low tidal volume (6 ml/kg) or high tidal volume (12 ml/kg) mechanical ventilation. Under low tidal volume conditions, rats administered oxidized surfactant had impaired lung function, as determined by lung compliance and arterial blood gas analysis, compared with nonoxidized controls. Animals subjected to high tidal volume ventilation had impaired lung function compared with low tidal volume groups, regardless of the oxidative status of the surfactant. The second experiment demonstrated a significantly superior physiological response in surfactant-deficient rats receiving SP-A containing oxidized surfactant compared with oxidized surfactant. Lavage analysis at the end of the in vivo experimentation showed no differences in the recovery of oxidized surfactant compared with nonoxidized surfactant. We conclude that minimizing excessive lung stretch during mechanical ventilation is important in the context of exogenous surfactant supplementation and that SP-A has an important biophysical role in surfactant function in conditions of oxidative stress. Furthermore, the oxidative status of the surfactant does not appear to affect the alveolar metabolism of this material.
authors.affiliation: Lawson Health Research Institute, Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario N6A 4V2, Canada.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Bailey
authors.forename: Adam A
authors.initials: AA
authors.lastname: Maruscak
authors.forename: Anne
authors.initials: A
authors.lastname: Petersen
authors.forename: Sarah
authors.initials: S
authors.lastname: White
authors.forename: James F
authors.initials: JF
authors.lastname: Lewis
authors.forename: Ruud A W
authors.initials: RA
authors.lastname: Veldhuizen
mesh_terms: D000818:Animals; D001158:Arteries; D001784:Blood Gas Analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004338:Drug Combinations; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008170:Lung Compliance; D008297:Male; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D037662:Pulmonary Surfactant-Associated Protein A / Q000032:analysis / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D013990:Tidal Volume
chemical_list: D004338:Drug Combinations; D037662:Pulmonary Surfactant-Associated Protein A; D011663:Pulmonary Surfactants