Development and Resuscitation of a Sedated, Mature Male Miniature Swine Severe Hemorrhage Model

Background: A sedated, mature male miniature swine hemorrhage model has been specifically developed to evaluate resuscitation products for the Defense Advanced Research Projects Agency Surviving Blood Loss program. Methods: Animals were placed in a sling, sedated with midazolam, and hemorrhaged 60% of estimated blood volume (similar to 39 mL/kg) exponentially for 1 hour with no resuscitation (control; n = 16). An additional 26 swine were treated similarly, then resuscitated with 1 mL/kg/min of Hextend to a systolic blood pressure of either 65 mm Hg +/- 2 mm Hg (n = 7) or 80 mm Hg +/- 5 mm Hg (n = 7) and with 17 beta-estradiol (E2) at 1 mg/kg (n = 6) or 10 mg/kg (n = 6). Animals were observed for 3 hours with periodic blood sampling. Survival times for the two E2 groups were not significantly different (p = 0.59); therefore, the groups were combined for comparison with control. Results: Hemorrhage resulted in a characteristic hypotension and metabolic acidosis. Survival time for the control swine was 64 minutes +/- 11.5 minutes with a 6% survival at 180 minutes. The 180 minutes Hextend survival was 86% for 65 mm Hg and 100% for 80 mm Hg. E2 survival was 125 minutes +/- 15.3 minutes, significantly different from control (p = 0.01), but E2 survival of 25% at 180 minutes was not different from control. Conclusion: A sedated, sexually mature male miniature swine severe hemorrhage model has been successfully developed, resuscitated with Hextend and used to evaluate E2 as a small volume resuscitation product.