In the event of a nuclear detonation, a considerable number of projected casualties will suffer from combined radiation exposure and
burn and/or
wound injury. Countermeasure assessment in the setting of radiation exposure combined with dermal injury is hampered by a lack of animal models in which the effects of interventions have been characterized. To address this need, we used two separate models to characterize
wound closure. The first was an open
wound model in mice to study the effect of
wound size in combination with whole-body 6 Gy irradiation on the rate of
wound closure, animal weight and survival (morbidity). In this model the addition of interventions,
wound closure, subcutaneous vehicle injection, topical
antiseptic and topical
antibiotics were studied to measure their effect on healing and survival. The second was a rat closed
wound model to study the biomechanical properties of a healed
wound at 10 days postirradiation (irradiated with 6 or 7.5 Gy). In addition, complete blood counts were performed and
wound pathology by staining with
hematoxylin and
eosin, trichrome, CD68 and Ki67. In the mouse open
wound model, we found that
wound size and morbidity were positively correlated, while
wound size and survival were negatively correlated. Regardless of the
wound size, the addition of radiation exposure delayed the healing of the
wound by approximately 5-6 days. The addition of interventions caused, at a minimum, a 30% increase in survival and improved mean survival by ∼9 days. In the rat closed
wound model we found that radiation exposure significantly decreased all
wound biomechanical measurements as well as white blood cell, platelet and red blood cell counts
at 10 days post wounding. Also, pathological changes showed a loss of dermal structure, thickening of dermis, loss of
collagen/epithelial
hyperplasia and an increased density of macrophages. In conclusion, we have characterized the effect of a changing
wound size in combination with radiation exposure. We also demonstrated that the most effective interventions mitigated insensible fluid loss, which could help to define the most appropriate requirements of a successful countermeasure.