title: Dose- and time-dependent effects of lipopolysaccharide on technetium-99-m-labeled diethylene-triamine pentaacetatic acid clearance, respiratory system mechanics and pulmonary inflammation.
abstract: Intratracheal administration of lipopolysaccharide (LPS) in animals is a commonly used model of acute lung injury, characterized by increased alveolar-capillary membrane permeability causing protein-rich edema, inflammation, deterioration of lung mechanical function and impaired gas exchange. Technetium-99-m-labeled diethylene-triamine pentaacetatic acid ((99m)Tc-DTPA) scintigraphy is a non-invasive technique to assess lung epithelial permeability. We hypothesize that the longer the exposure and the higher the dose of LPS the greater the derangement of the various indices of lung injury. After 3, 6 and 24 h of 5 or 40 μg LPS intratracheally administration, (99m)Tc-DTPA was instilled in the lung. Images were acquired for 90 min with a γ-camera and the radiotracer clearance was estimated. In another subgroup, the mechanical properties of the respiratory system were estimated with the forced oscillation technique and static pressure-volume curves, 4.5, 7.5 and 25.5 h post-LPS (iso-times with the end of (99m)Tc-DTPA scintigraphy). Bronchoalveolar lavage (BAL) was performed and a lung injury score was estimated by histology. Lung myeloperoxidase (MPO) activity was measured. (99m)Tc-DTPA clearance increased in all LPS challenged groups compared with control. DTPA clearance presented a U-shape time course at the lower dose, while LPS had a declining effect over time at the larger dose. At 7.5 and 25.5 h post-LPS, tissue elasticity was increased and static compliance decreased at both doses. Total protein in the BAL fluid increased at both doses only at 4.5 h Total lung injury score and MPO activity were elevated in all LPS-treated groups. There is differential time- and dose-dependency of the various indices of lung injury after intratracheally LPS instillation in rats.
authors.affiliation: Department of Critical Care and Pulmonary Services, G.P. Livanos, M. Simou and Experimental Surgery Laboratories, University of Athens, Medical School, Evangelismos Hospital, Athens, Greece.
authors.forename: George A
authors.initials: GA
authors.lastname: Kastis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Toumpanakis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Loverdos
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Anaplioti
authors.forename: Alexandros
authors.initials: A
authors.lastname: Samartzis
authors.forename: Pinelopi
authors.initials: P
authors.lastname: Argyriou
authors.forename: George
authors.initials: G
authors.lastname: Loudos
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Karavana
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Tzouda
authors.forename: Ioannis
authors.initials: I
authors.lastname: Datseris
authors.forename: Demetra
authors.initials: D
authors.lastname: Rontogianni
authors.forename: Charalampos
authors.initials: C
authors.lastname: Roussos
authors.forename: Stamatios E
authors.initials: SE
authors.lastname: Theocharis
authors.forename: Theodoros
authors.initials: T
authors.lastname: Vassilakopoulos
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004548:Elasticity; D006651:Histocytochemistry; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology; D008657:Metabolic Clearance Rate; D009195:Peroxidase / Q000032:analysis; D011014:Pneumonia / Q000473:pathology*; D011506:Proteins / Q000032:analysis; D011859:Radiography; D011877:Radionuclide Imaging / Q000379:methods; D051381:Rats; D012137:Respiratory System / Q000503:physiopathology*; D016284:Technetium Tc 99m Pentetate / Q000493:pharmacokinetics*
chemical_list: D008070:Lipopolysaccharides; D011506:Proteins; D009195:Peroxidase; D016284:Technetium Tc 99m Pentetate