Significance of bioindicators to predict survival in irradiated minipigs.

Abstract

The minipig is emerging as a potential alternative non-rodent animal model. Several biological markers (e.g., blood counts, laboratory parameters, and clinical signs) have been proposed for rapid triage of radiation victims. Here, the authors focus on the significance of bio-indicators for prediction of survivors after irradiation and compare it with human data; the relationship between these biomarkers and radiation dose is not part of this study. Male Göttingen minipigs (age 4-5 mo, weight 9-10 kg) were irradiated (or sham-irradiated) bilaterally with gamma-photons (⁶⁰Co, 0.5-0.6 Gy min⁻¹) in the dose range of 1.6-12 Gy. Peripheral blood cell counts, laboratory parameters, and clinical symptoms were collected up to 10 d 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). However, most predictive within the first 3 d 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 this 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.