title: Protective effects of elevated endogenous surfactant pools to injurious mechanical ventilation.
abstract: Depletion of alveolar macrophages (AM) leads to an increase in endogenous surfactant that lasts several days beyond the repletion of AM. Furthermore, impairment to the endogenous pulmonary surfactant system contributes to ventilation-induced lung injury. The objective of the current study was to determine whether increased endogenous surfactant pools induced via AM depletion was protective against ventilation-induced lung injury. Adult rats were intratracheally instilled with either control or dichloromethylene diphosphonic acid (DMDP) containing liposomes to deplete AMs and thereby increase endogenous surfactant pools. Either 3 or 7 days following instillation, rats were exposed to 2 h of injurious ventilation using either an ex vivo or in vivo ventilation protocol and were compared with nonventilated controls. The measured outcomes were oxygenation, lung compliance, lavage protein, and inflammatory cytokine concentrations. Compared with controls, the DMDP-treated animals had significantly reduced AM numbers and increased surfactant pools 3 days after instillation. Seven days after instillation, AM numbers had returned to normal, but surfactant pools were still elevated. DMDP-treated animals at both time points exhibited protection against ventilation-induced lung injury, which included superior physiological parameters, lower protein leakage, and lower inflammatory mediator release into the air space, compared with animals not receiving DMDP. It is concluded that DMDP-liposome administration protects against ventilation-induced lung injury. This effect appears to be due to the presence of elevated endogenous surfactant pools.
authors.affiliation: Department of Medicine, Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada. rveldhui@uwo.ca
authors.forename: Cory
authors.initials: C
authors.lastname: Yamashita
authors.forename: Amy
authors.initials: A
authors.lastname: Forbes
authors.forename: Jenna M
authors.initials: JM
authors.lastname: Tessolini
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Yao
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; D004002:Clodronic Acid / Q000494:pharmacology*; D008081:Liposomes; D008171:Lung Diseases / Q000209:etiology / Q000517:prevention & control*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011663:Pulmonary Surfactants / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
chemical_list: D008081:Liposomes; D011663:Pulmonary Surfactants; D004002:Clodronic Acid