title: Vitamin A is systemically bioavailable after intratracheal administration with surfactant in an animal model of newborn respiratory distress.
abstract: Chronic lung disease (CLD) is a major cause of long-term morbidity in extremely LBW infants with respiratory distress syndrome. Parenteral vitamin A administration decreases the risk of CLD. We tested the hypothesis that intratracheal vitamin A administration with surfactant is systemically bioavailable without interfering with the functional properties of exogenous surfactant. Newborn piglets were ventilated with 100% FiO2 and sequential saline lavage induced respiratory distress syndrome. During lung injury induction, ventilator changes were allowed, but none were made following treatment allocation. Animals were assigned by chance in a blinded control trial to three groups: I=control; II=surfactant; III=surfactant+vitamin A. Hemodynamics, lung mechanics, and blood gases were measured following instrumentation, pre- and posttreatment for 4 h, at which time the liver was sampled for retinol determination. All parameters improved in animals receiving surfactant. A significant interaction existed between time and group for PaO2 and alveolar-arterial oxygen difference (A-aDO2). Hepatic levels of retinol were higher (p<0.001) in animals receiving retinyl acetate. Intratracheal administration of surfactant+vitamin A did not alter the beneficial effects of surfactant on lung compliance and gas exchange. Intratracheal Vitamin A was associated with rapid hepatic uptake. Further studies are warranted.
authors.affiliation: Department of Pediatrics, Children's and Women's Health Center of British Columbia, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V4.
authors.forename: Avash J
authors.initials: AJ
authors.lastname: Singh
authors.forename: Vadim
authors.initials: V
authors.lastname: Bronshtein
authors.forename: Minesh
authors.initials: M
authors.lastname: Khashu
authors.forename: Kyle
authors.initials: K
authors.lastname: Lee
authors.forename: James E
authors.initials: JE
authors.lastname: Potts
authors.forename: James
authors.initials: J
authors.lastname: Friel
authors.forename: Philippe
authors.initials: P
authors.lastname: Chessex
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D001682:Biological Availability; D004195:Disease Models, Animal; D004224:Diterpenes; D004338:Drug Combinations; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D007442:Intubation, Intratracheal; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008170:Lung Compliance / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011663:Pulmonary Surfactants / Q000008:administration & dosage*; D012127:Respiratory Distress Syndrome, Newborn / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D000084562:Retinyl Esters; D013552:Swine; D013997:Time Factors; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014815:Vitamins / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D004224:Diterpenes; D004338:Drug Combinations; D011663:Pulmonary Surfactants; D000084562:Retinyl Esters; D014815:Vitamins; D014801:Vitamin A; C009166:retinol acetate; D010100:Oxygen