Trauma-related hemorrhagic shock (HS) remains a leading cause of death among military and civilian trauma patients. We have previously shown that administration of complement and HMGB1 inhibitors attenuate morbidity and mortality 24 h after injury in a rat model of blast injury (BI) and HS. To further validate these results, this study aimed to develop a swine model and evaluate BI+HS-induced pathophysiology. Anesthetized Yucatan minipigs underwent combined BI and volume-controlled hemorrhage. After 30 min of shock, animals received an intravenous bolus of PlasmaLyte A and a continuous PlasmaLyte A infusion. The survival rate was 80% (4/5), and the non-survivor expired 72 min post-BI. Circulating organ-functional biomarkers, inflammatory biomarkers, histopathological evaluation, and CT scans indicated evidence of multiple-organ damage, systemic innate immunological activation, and local tissue inflammation in the injured animals. Interestingly, a rapid and dramatic increase in plasma levels of HMGB1 and C3a and markedly early myocarditis and encephalitis were associated with early death post-BI+HS. This study suggests that this model reflects the immunopathological alterations of polytrauma in humans during shock and prolonged damage control resuscitation. This experimental protocol could be helpful in the assessment of immunological damage control resuscitation approaches during the prolonged care of warfighters.
Keywords: blast injury; fluid resuscitation; hemorrhagic shock; immunopathology; organ damage; polytrauma.