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 the functional disorders ensuing pulmonary intoxication, a prerequisite for establishing a clinically-relevant therapeutic protocol, is hampered by the lack of an appropriate animal model. To this end, we set up 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-intoxicated pigs. Up to 30 hours 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 robust elevation in respiratory rate with minimal response in tidal volume. This response was followed by decompensation, manifested by a descent in Minute Volume and severe hypoxemia, refractory to oxygen treatment. Radiological evaluation revealed evidence of early diffuse bi-lateral 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 while histological studies revealed lung tissue insults accumulating over time, up to the development of 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 Acute Respiratory Distress Syndrome. The establishment of this animal model of pulmonary ricinosis, should assist us in our pursuit of efficient medical countermeasures, specifically-tailored to deal with the respiratory deficiencies stemming from ricin-induced Acute Respiratory Distress Syndrome.