title: Physiological, Biochemical, and Biophysical Characterization of the Lung-Lavaged Spontaneously-Breathing Rabbit as a Model for Respiratory Distress Syndrome.
abstract: Nasal continuous positive airway pressure (nCPAP) is a widely accepted technique of non-invasive respiratory support in spontaneously-breathing premature infants with respiratory distress syndrome (RDS). Surfactant administration techniques compatible with nCPAP ventilation strategy are actively investigated. Our aim is to set up and validate a respiratory distress animal model that can be managed on nCPAP suitable for surfactant administration techniques studies. Surfactant depletion was induced by bronchoalveolar lavages (BALs) on 18 adult rabbits. Full depletion was assessed by surfactant component analysis on the BALs samples. Animals were randomized into two groups: Control group (nCPAP only) and InSurE group, consisting of a bolus of surfactant (Poractant alfa, 200 mg/kg) followed by nCPAP. Arterial blood gases were monitored until animal sacrifice, 3 hours post treatment. Lung mechanics were evaluated just before and after BALs, at the time of treatment, and at the end of the procedure. Surfactant phospholipids and protein analysis as well as surface tension measurements on sequential BALs confirmed the efficacy of the surfactant depletion procedure. The InSurE group showed a significant improvement of blood oxygenation and lung mechanics. On the contrary, no signs of recovery were appreciated in animals treated with just nCPAP. The surfactant-depleted adult rabbit RDS model proved to be a valuable and efficient preclinical tool for mimicking the clinical scenario of preterm infants affected by mild/moderate RDS who spontaneously breathe and do not require mechanical ventilation. This population is of particular interest as potential target for the non-invasive administration of surfactant.
authors.affiliation: Chiesi Farmaceutici, R&D Department, Parma, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ricci
authors.affiliation: Chiesi Farmaceutici, R&D Department, Parma, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Catozzi
authors.affiliation: Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany.
authors.forename: Xabier
authors.initials: X
authors.lastname: Murgia
authors.affiliation: Chiesi Farmaceutici, R&D Department, Parma, Italy.
authors.forename: Brenda
authors.initials: B
authors.lastname: Rosa
authors.affiliation: Department of Life Sciences, University of Parma, Parma, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Amidani
authors.affiliation: Chiesi Farmaceutici, R&D Department, Parma, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Lorenzini
authors.affiliation: Chiesi Farmaceutici, R&D Department, Parma, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Bianco
authors.affiliation: Department of Life Sciences, University of Parma, Parma, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Rivetti
authors.affiliation: Chiesi Farmaceutici, R&D Department, Parma, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Catinella
authors.affiliation: Chiesi Farmaceutici, R&D Department, Parma, Italy.
authors.forename: Gino
authors.initials: G
authors.lastname: Villetti
authors.affiliation: Chiesi Farmaceutici, R&D Department, Parma, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Civelli
authors.affiliation: Chiesi Farmaceutici, R&D Department, Parma, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pioselli
authors.affiliation: Department of Neurosciences, Psychology, Drug Research and Child Health, Careggi University Hospital of Florence, Florence, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Dani
authors.affiliation: Chiesi Farmaceutici, R&D Department, Parma, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Salomone
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D002853:Chromatography, Liquid; D045422:Continuous Positive Airway Pressure; D004195:Disease Models, Animal; D013058:Mass Spectrometry; D008962:Models, Theoretical; D010743:Phospholipids / Q000097:blood; D011663:Pulmonary Surfactants / Q000008:administration & dosage; D011817:Rabbits; D011897:Random Allocation; D012127:Respiratory Distress Syndrome, Newborn / Q000503:physiopathology*; D013501:Surface-Active Agents
chemical_list: D010743:Phospholipids; D011663:Pulmonary Surfactants; D013501:Surface-Active Agents