title: Time- and dose-dependent severity of lung injury in a rat model of sepsis.
abstract: Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Lipopolysaccharide (LPS) administration is the most often used approach to model the consequences of bacterial sepsis. We created an endotoxemia rat model, simulating sepsis-related lung injury, in order to quantify the time and dose dependent severity lesions induced by the administration of lipopolysaccharide. Our study included 42 male Wistar rats, randomly divided into four groups: one control group (n=6) and three experimental groups (n=12/group) in whom we induced sepsis by intraperitoneal injection of progressively increasing doses of LPS (3, 5, 10 mg/kg). At six hours, the animals included in the groups with higher doses of LPS developed thrombocytopenia, elevated lactate levels, and liver and renal injury in a dose and time dependent manner. The severity of hypoxemia at six hours correlated with the increasing doses of LPS, with a slight improvement at 24 hours. Lung injury scores became more severe with increased dose and time of exposure to LPS without reaching the level of hyaline membranes formation. We also demonstrated translocation of a protein from the airspaces into plasma (RAGE - receptor for advanced glycation end products). Induction of sepsis using LPS is a known experimental model, but LPS treatment in rats does not cause the severe endothelial and epithelial injury that occurs in humans with acute respiratory distress syndrome (ARDS). In our study, the clinical, laboratory and histopathological findings confirmed sepsis and the damage of the alveolar-capillary membrane in a dose-dependent manner.
authors.affiliation: Department of Infectious Diseases, University of Medicine and Pharmacy of Tirgu Mures, Romania; ancameda.georgescu@umftgm.ro.
authors.forename: Raluca-Ştefania
authors.initials: RŞ
authors.lastname: Fodor
authors.forename: Anca Meda
authors.initials: AM
authors.lastname: Georgescu
authors.forename: Adrian-Dan
authors.initials: AD
authors.lastname: Cioc
authors.forename: Bianca Liana
authors.initials: BL
authors.lastname: Grigorescu
authors.forename: Ovidiu Simion
authors.initials: OS
authors.lastname: Cotoi
authors.forename: Pal
authors.initials: P
authors.lastname: Fodor
authors.forename: Sanda Maria
authors.initials: SM
authors.lastname: Copotoiu
authors.forename: Leonard
authors.initials: L
authors.lastname: Azamfirei
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001158:Arteries / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001784:Blood Gas Analysis; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000378:metabolism; D004195:Disease Models, Animal; D004848:Epithelium / Q000473:pathology; D007249:Inflammation / Q000150:complications / Q000473:pathology; D019344:Lactic Acid / Q000378:metabolism; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D008168:Lung / Q000473:pathology; D055370:Lung Injury / Q000097:blood / Q000150:complications* / Q000473:pathology*; D008297:Male; D010100:Oxygen / Q000378:metabolism; D010976:Platelet Count; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D018805:Sepsis / Q000097:blood / Q000150:complications* / Q000473:pathology*; D013997:Time Factors
chemical_list: C000593874:Ager protein, rat; D008070:Lipopolysaccharides; D000067759:Receptor for Advanced Glycation End Products; D019344:Lactic Acid; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010100:Oxygen