A Combat-Relevant Model of Traumatic Hemorrhage in Rats for the Study of Combined Radiation Injury: A Pilot Study

The threat and consequences of nuclear or radiological events remain a military concern today. It is estimated that 65-70% of weapon-related injuries after a nuclear event will be radiation combined injuries, i. e., acute radiation injury along with hemorrhage and traumatic injuries such as blast or other burns, bone fractures, soft tissue injuries, blood loss, and/or hypoxia. However, little is known about most types of traumatic injuries associated with blood loss, as might occur during combat operations. The primary objective of this pilot study was to develop a new animal model that incorporates both hemorrhage and traumatic injury, combined with radiation exposure. Male Sprague-Dawley rats were divided into four groups (6/group): 1. sham; 2. radiation injury (RI); 3. traumatic hemorrhage (TH), which is hemorrhage combined with extremity trauma; and 4. RI+TH. Radiation injury consisted of a single X-ray dose of 5. 5.5 Gy delivered at a rate of 1 Gy/min. Hemorrhage involved a stepwise reduction of 37% of the estimated blood volume. Extremity trauma consisted of fibular fractures and penetrating and soft tissue injuries to a single extremity. Heart rate, mean arterial blood pressure (MAP), and blood indices were analyzed at intervals corresponding to pre-hemorrhage, end of hemorrhage, and 4 h after hemorrhage, with survival observed for 14 days. Radiation injury alone had little impact on the measured variables. Hemorrhage resulted in a 60% and 67% reduction in MAP in the traumatic hemorrhage and RI+TH groups, respectively, immediately after hemorrhage, which recovered by 4 h in the traumatic hemorrhage group but not in RI+TH group. A similar pattern was observed for blood lactate levels. Traumatic hemorrhage and radiation injury resulted in 50% mortality, although mortality occurred earlier after traumatic hemorrhage. RI+TH produced 80% mortality by day 4. No mortality was observed in the sham group. By combining a high dose of X-ray radiation with our established model of traumatic hemorrhage, we have developed a new rodent model that mimics combat casualties during nuclear or radiological events.