Combined injuries, which are expected after a radiation dispersal device release or nuclear weapon detonation, are the combination of radiation exposure and tissue injuries from blast and thermal energy. To determine the impact of such trauma, mice were used to (1) evaluate the consequences of skin tissue injuries after various qualities and doses of radiation and (2) document substances that increase survival from radiation injury. Female 12- to 20-wk-old mice weighing 23 +/- 3 g received dorsal skin burns or wounds (15% total body skin surface) under methoxyflurane anesthesia before or after irradiation in this study approved by the Armed Forces Radiobiology Research Institute (AFRRI) Institutional Animal Care and Use Committee. Methoxyflurane is analgesic up to 48 h after injury. The radiations used in these studies included Co gamma photons (1.25 MeV) and research-reactor-produced neutrons with an average energy of 0.96 MeV in either an enriched-field [n/(n + gamma) = 0.95] configuration at 4.2 kW or a mixed-field [n/(n + gamma) = 0.67] configuration operated at 45 kW. Dose rates averaged 0.4 Gy/min. Endpoints included survival, LD50/30s (lethal dose to produce 50% mortality in 30 d), dose modifying factors, relative biological effectiveness values, tissue alterations, susceptibility to bacterial challenge, and countermeasure efficacies. Countermeasures evaluated included S-3-(3-methylaminopropylamino) propylthiophosphorothioic acid (WR-151327), antibiotics, immune modulators, and bone marrow transplantation. Of these treatments, survival was improved by WR-151327, antibiotics, synthetic trehalose discorynomycolate, and bone marrow transplantation. Because trauma to irradiated personnel and medical countermeasures may affect biodosimetric measurements, it will be necessary to quickly determine radiation dose in order to implement appropriate therapy.
