title: Postexposure aerosolized heparin reduces lung injury in chlorine-exposed mice.
abstract: Chlorine (Cl2) is a highly reactive oxidant gas that, when inhaled, may cause acute lung injury culminating in death from respiratory failure. In this study, we tested the hypothesis that exposure of mice to Cl2 causes intra-alveolar and systemic activation of the coagulation cascade that plays an important role in development of lung injury. C57Bl/6 mice were exposed to Cl2 (400 for 30 min or 600 ppm for 45 min) in environmental chambers and then returned to room air for 1 or 6 h. Native coagulation (NATEM) parameters such as blood clotting time and clot formation time were measured in whole blood by the viscoelastic technique. D-dimers and thrombin-anti-thrombin complexes were measured in both plasma and bronchoalveolar lavage fluid (BALF) by ELISA. Our results indicate that mice exposed to Cl2 gas had significantly increased clotting time, clot formation time, and D-dimers compared with controls. The thrombin-anti-thrombin complexes were also increased in the BALF of Cl2 exposed animals. To test whether increased coagulation contributed to the development of acute lung injury, mice exposed to Cl2 and returned to room air were treated with aerosolized heparin or vehicle for 20 min. Aerosolized heparin significantly reduced protein levels and the number of inflammatory cells in the BALF at 6 h postexposure. These findings highlight the importance of coagulation abnormities in the development of Cl2-induced lung injury.
authors.affiliation: Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and Center for Pulmonary Injury and Repair, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Sotirios G
authors.initials: SG
authors.lastname: Zarogiannis
authors.affiliation: Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and.
authors.forename: Brant M
authors.initials: BM
authors.lastname: Wagener
authors.affiliation: Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and.
authors.forename: Susanna
authors.initials: S
authors.lastname: Basappa
authors.affiliation: Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and.
authors.forename: Stephen
authors.initials: S
authors.lastname: Doran
authors.affiliation: Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and.
authors.forename: Cilina A
authors.initials: CA
authors.lastname: Rodriguez
authors.affiliation: Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and Center for Pulmonary Injury and Repair, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Asta
authors.initials: A
authors.lastname: Jurkuvenaite
authors.affiliation: Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and Center for Pulmonary Injury and Repair, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Jean Francois
authors.initials: JF
authors.lastname: Pittet
authors.affiliation: Department of Anesthesiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and Center for Pulmonary Injury and Repair, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama sadis@uab.edu.
authors.forename: Sadis
authors.initials: S
authors.lastname: Matalon
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002713:Chlorine / Q000633:toxicity*; D004195:Disease Models, Animal; D005342:Fibrinolysis / Q000187:drug effects; D006493:Heparin / Q000008:administration & dosage*; D055370:Lung Injury / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D000925:Anticoagulants; D002619:Chemical Warfare Agents; D002713:Chlorine; D006493:Heparin
keywords: D-dimer; acute lung injury; clotting time; coagulation; thrombin