H. He1,2, P. L. Jernigan1,2, R. S. Hoehn1,2, A. L. Chang1,2, L. Friend1,2, R. Veile1,2, T. Johannigman1,2, A. T. Makely1,2, M. D. Goodman1,2, T. A. Pritts1,2 1University Of Cincinnati,Trauma And Critical Care,Cincinnati, OH, USA 2University Of Cincinnati,Institute For Military Medicine,Cincinnati, OH, USA
Introduction: Hemorrhagic shock is the leading cause of potentially preventable death after trauma. The optimal treatment for hemorrhagic shock is to reverse circulatory losses, metabolic acidosis, and cellular hypoxia with blood products, but these are often not available for immediate administration. Alternative approaches to initial resuscitation are needed, especially in resource poor environments. Amitriptyline is a serotonin-norepinephrine reuptake inhibitor with anti-inflammatory effects. We have previously demonstrated that treatment of blood products with amitriptyline leads to decreased lung injury after hemorrhage, but the direct effect of amitriptyline in treatment of hemorrhage is unknown. We hypothesized that administration of amitriptyline after trauma and hemorrhage would improve survival in a non-resuscitation injury model.
Methods: Healthy C57/BL6 male mice underwent laparotomy to induce tissue trauma and hemorrhage via femoral artery cannulation to a mean arterial pressure of 25±5mmHg for 60 minutes. After laparotomy closure and decannulation, mice received amitriptyline (0.1 mg/kg) or an equivalent volume of vehicle (50 uL of normal saline) via intraperitoneal injection. For survival analysis, mice underwent the above treatment (n=10/group) and were monitored for 24 hours. For hemodynamic and blood chemistry analysis, mice (n=5/group) underwent the same injuries and treatments as described above and were sacrificed 60 minutes after treatment.
Results: Administration of amitriptyline after trauma and hemorrhage significantly increased 24-hour survival in mice (Figure 1; 70% survival with amitriptyline vs 0% with vehicle; p<0.001). Sixty minutes after trauma and hemorrhage, mice treated with amitriptyline also had significantly increased mean arterial blood pressure (p=0.04). Blood gas analysis revealed that mice treated with amitriptyline had statistically significant improvements in base deficit and serum bicarbonate, consistent with decreased metabolic acidosis.
Conclusion: Our results demonstrate that administration of amitriptyline significantly improves survival in mice after trauma and hemorrhage, even in the absence of resuscitation. We found that amitriptyline increases mean arterial blood pressure and decreases metabolic acidosis after injury. Administration of amitriptyline following traumatic injury could potentially be useful in situations with limited access to blood products.
