title: Alveolar environment influences the metabolic and biophysical properties of exogenous surfactants.
abstract: Several factors have been shown to influence the efficacy of exogenous surfactant therapy in the acute respiratory distress syndrome. We investigated the effects of four different alveolar environments (control, saline-lavaged, N-nitroso-N-methylurethane, and hydrochloric acid) on the metabolic and functional properties of two exogenous surfactant preparations: bovine lipid extract surfactant and recombinant surfactant-associated protein (SP) C drug product (rSPC) administered to each of these groups. The main difference between these preparations was the lack of SP-B in the rSPC. Our results demonstrated differences in the large aggregate pool sizes recovered from each of the experimental groups. We also observed differences in SP-A content, surface area cycling characteristics, and biophysical activities of these large aggregate forms after the administration of the two exogenous surfactant preparations. We conclude that the alveolar environment plays a critical role, influencing the overall efficacy of exogenous surfactant therapy. Thus further preclinical studies are warranted to investigate the specific factors within the alveolar environment that lead to the differences observed in this study.
authors.affiliation: Departments of Physiology and Medicine and Lawson Research Institute, Medical Research Council Group in Fetal and Neonatal Health and Development, London Health Sciences Centre, The University of Western Ontario, London, Ontario, Canada N6A 4.
authors.forename: P S
authors.initials: PS
authors.lastname: Puligandla
authors.forename: T
authors.initials: T
authors.lastname: Gill
authors.forename: L A
authors.initials: LA
authors.lastname: McCaig
authors.forename: L J
authors.initials: LJ
authors.lastname: Yao
authors.forename: R A
authors.initials: RA
authors.lastname: Veldhuizen
authors.forename: F
authors.initials: F
authors.lastname: Possmayer
authors.forename: J F
authors.initials: JF
authors.lastname: Lewis
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002417:Cattle; D006801:Humans; D006851:Hydrochloric Acid / Q000633:toxicity; D009605:Nitrosomethylurethane / Q000633:toxicity; D011510:Proteolipids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000378:metabolism
chemical_list: D011510:Proteolipids; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D009605:Nitrosomethylurethane; D006851:Hydrochloric Acid