Comparative Efficacy Study of Two FDA Approved Complement Inhibitors in Pre-Hospital and Early Hospital Model of Traumatic Hemorrhage in Swine
Abstract
Prompt control of hemorrhage and adequate resuscitation are critical elements in managing hemorrhage patients. Conventional fluid resuscitation is designed to reestablish tissue perfusion; however, it fails to reduce concomitant inflammatory and coagulopathic responses. In fact, fluid resuscitation can further heighten inflammatory responses, worsen coagulopathy, and cause further cellular damage, all of which exacerbate trauma/hemorrhagic injury. The dysfunctional immune response triggered by trauma/hemorrhage is the basis for subsequent development of Multiple Organ Dysfunction (MOD). Early MOD is attributed to an overwhelming leukocyte driven pro-inflammatory response clinically defined as systemic inflammatory response syndrome (SIRS). Treatment with blood products or by targeting individual immune components has not improved clinical outcomes of inflammatory complications after trauma. Targeting the complement cascade is an alternative approach that could be employed to indirectly dampen multiple downstream immune effector functions that are activated during traumatic hemorrhage. The aim of our study was to compare the efficacy of a Complement C1 inhibitor (C1INH) and a Complement C5 inhibitor. Unfortunately, the partner responsible for providing the Complement C5 inhibitor withdrew their support prior to the start of this work. Through subsequent analysis of our findings from the model development process, it was determined that examining the effect of splenectomy on surgical outcomes and immune response would be the most judicious use of the remainder of the funds associated with this project.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 08, 2024
- Accession Number
- AD1227721
Entities
People
- Alexander H. Penn
- Chester Hutcheson
Organizations
- 59th Medical Wing