A novel swine model of ricin-induced acute respiratory distress syndrome

Shahaf Katalan, Reut Falach, Amir Rosner, Michael Goldvaser, Tal Brosh-Nissimov, Ayana Dvir, Avi Mizrachi, Orr Goren, Barak Cohen, Yoav Gal, Anita Sapoznikov, Sharon Ehrlich, Tamar Sabo, Chanoch Kronman

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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 ricininduced 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.

Original languageEnglish
Pages (from-to)173-183
Number of pages11
JournalDMM Disease Models and Mechanisms
Volume10
Issue number2
DOIs
StatePublished - 1 Feb 2017
Externally publishedYes

Keywords

  • ARDS
  • Animal model
  • Inflammation
  • Lung permeability
  • Pig
  • Ricin

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • General Biochemistry, Genetics and Molecular Biology

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