Significance of bioindicators to predict survival in irradiated minipigs.

The minipig is emerging as a potential alternative non-rodent animal model. Several biological markers e.g. blood counts, laboratory parameter and clinical signs have been proposed for rapid triage of radiation victims. Here, we focus on the significance of bio-indicators for prediction of survivors after irradiation and compared it with human data; relationship between these biomarkers and radiation dose is not part of this study. Male Gottingen minipigs (age 4–5 months, weight 9–10 kg) were irradiated (or sham-irradiated) bilaterally with gamma-photons (Cobalt-60, 0.5–0.6 Gy/min) in the dose range of 1.6 – 12 Gy. Peripheral blood cell counts, laboratory parameters, and clinical symptoms were collected up to 10 days after irradiation and analyzed using logistic regression analysis and calculating ROC curves. In moribund pigs parameters such as decreased lymphocyte/granulocyte counts, increased C-reactive protein, alkaline phosphatase values as well as increased citrulline values and body temperature significantly (p<0.002 up to p<0.0001) discriminated non-survivors from survivors with high precision (ROC ≥ 0.8), but most predictive within the first three days after exposure was a combination of decreased lymphocyte counts and increased body temperature observed as early as 3 h after radiation exposure (ROC: 0.93–0.96, p<0.0001). Sham-irradiated animals (corresponding to “worried wells”) could be easily discriminated from dying pigs, thus pointing to the diagnostic significance of our analysis. These data corroborate with earlier findings performed on human radiation victims suffering from severe hematological syndrome and provide further evidence for the suitability of the minipig model as a potential alternative non-rodent animal model.