Pathophysiological profile of awake and anesthetized pigs following systemic exposure to the highly lethal ricin toxin.

Ricin, a plant-derived toxin originating from the seeds of Ricinus communis (castor bean plant), is one of the most lethal toxins known. To date, no in-depth study of systemic exposure to ricin in a standardized large animal model has been reported. This study details for the first time the pathophysiological hemodynamic profile following systemic/intramuscular exposure to the ricin toxin in a porcine model by comprehensive cardiorespiratory monitoring of awake and anesthetized pigs. Unlike respiratory exposure to ricin, which is characterized by the development of acute respiratory distress syndrome, following intramuscular exposure to ricin respiratory parameters were grossly unaffected, however the hemodynamics of both awake and anesthetize pigs were unsustainably compromised. We show that in the early phase until approximately 24 h post-exposure, cardiac output is not impaired although one of its components, stroke volume, is relatively low. This is due to compensatory increase in heart rate, which eventually becomes insufficient. Later, distributive shock develops, characterized by severe vasodilatation (decreased systemic vascular resistance), low central venous oxygen saturation and elevation of venous-to-arterial carbon dioxide difference indicating increase in tissue oxygen demand not met by cardiac supply. These findings serve as a basis for further studies to evaluate the ability of supportive treatments such as vasoactive and inotropic drugs, to postpone the hemodynamic deterioration and thus expand the therapeutic window for the anti-ricin treatment. Such studies are of crucial importance for judicious treatment of victims of acts of bioterrorism or of intentional self-poisoning.

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

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.