title: A novel swine model of ricin-induced acute respiratory distress syndrome.
abstract: Pulmonary exposure to the plant toxin ricin leads to respiratory insufficiency and death. To date, in-depth study of acute respiratory distress syndrome (ARDS) following pulmonary exposure to toxins is hampered by the lack of an appropriate animal model. To this end, we established the pig as a large animal model for the comprehensive study of the multifarious clinical manifestations of pulmonary ricinosis. Here, we report for the first time, the monitoring of barometric whole body plethysmography for pulmonary function tests in non-anesthetized ricin-treated pigs. Up to 30 h post-exposure, as a result of progressing hypoxemia and to prevent carbon dioxide retention, animals exhibited a compensatory response of elevation in minute volume, attributed mainly to a large elevation in respiratory rate with minimal response in tidal volume. This response was followed by decompensation, manifested by a decrease in minute volume and severe hypoxemia, refractory to oxygen treatment. Radiological evaluation revealed evidence of early diffuse bilateral pulmonary infiltrates while hemodynamic parameters remained unchanged, excluding cardiac failure as an explanation for respiratory insufficiency. Ricin-intoxicated pigs suffered from increased lung permeability accompanied by cytokine storming. Histological studies revealed lung tissue insults that accumulated over time and led to diffuse alveolar damage. Charting the decline in PaO2/FiO2 ratio in a mechanically ventilated pig confirmed that ricin-induced respiratory damage complies with the accepted diagnostic criteria for ARDS. The establishment of this animal model of pulmonary ricinosis should help in the pursuit of efficient medical countermeasures specifically tailored to deal with the respiratory deficiencies stemming from ricin-induced ARDS.
authors.affiliation: Department of Pharmacology, Israel Institute for Biological Research, 7410001 Ness-Ziona, Israel shahafk@iibr.gov.il tamars@iibr.gov.il.
authors.forename: Shahaf
authors.initials: S
authors.lastname: Katalan
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, 7410001 Ness-Ziona, Israel.
authors.forename: Reut
authors.initials: R
authors.lastname: Falach
authors.affiliation: Veterinary Center for Preclinical Research, Israel Institute for Biological Research, 7410001 Ness-Ziona, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Rosner
authors.affiliation: Department of Organic Chemistry, Israel Institute for Biological Research, 7410001 Ness-Ziona, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Goldvaser
authors.affiliation: Infectious Disease Unit, Sheba Medical Center, 5262160 Tel-Hashomer, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Brosh-Nissimov
authors.affiliation: General Intensive Care Unit, Asaf Harofeh Medical Center, 70300 Zerifin, Israel.
authors.forename: Ayana
authors.initials: A
authors.lastname: Dvir
authors.affiliation: General Intensive Care Unit, Kaplan Medical Center, 7661041 Rehovot, Israel.
authors.forename: Avi
authors.initials: A
authors.lastname: Mizrachi
authors.affiliation: Anesthesia, Pain and Intensive Care Division, Tel-Aviv Medical Center, Tel-Aviv University, 6093000 Tel-Aviv, Israel.
authors.forename: Orr
authors.initials: O
authors.lastname: Goren
authors.affiliation: Anesthesia, Pain and Intensive Care Division, Tel-Aviv Medical Center, Tel-Aviv University, 6093000 Tel-Aviv, Israel.
authors.forename: Barak
authors.initials: B
authors.lastname: Cohen
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, 7410001 Ness-Ziona, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Gal
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, 7410001 Ness-Ziona, Israel.
authors.forename: Anita
authors.initials: A
authors.lastname: Sapoznikov
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, 7410001 Ness-Ziona, Israel.
authors.forename: Sharon
authors.initials: S
authors.lastname: Ehrlich
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, 7410001 Ness-Ziona, Israel shahafk@iibr.gov.il tamars@iibr.gov.il.
authors.forename: Tamar
authors.identifier: 0000-0001-8917-3669
authors.initials: T
authors.lastname: Sabo
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, 7410001 Ness-Ziona, Israel.
authors.forename: Chanoch
authors.initials: C
authors.lastname: Kronman
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D001831:Body Temperature; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D006863:Hydrogen-Ion Concentration; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D055370:Lung Injury / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D010539:Permeability; D011014:Pneumonia / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D011659:Pulmonary Gas Exchange; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000139:chemically induced* / Q000473:pathology* / Q000503:physiopathology; D012129:Respiratory Function Tests; D012276:Ricin; D013552:Swine
chemical_list: D016207:Cytokines; D019332:Endothelin-1; D018836:Inflammation Mediators; D012276:Ricin; D010100:Oxygen
keywords: ARDS; Animal model; Inflammation; Lung permeability; Pig; Ricin