The Effects of Tourniquet Associated Ischemia Reperfusion Injury on the Development of Secondary Injury in a Blast-Related Model of Lower Limb Extremity Trauma
Abstract
Blast accounted for 70% of all mechanisms of injury during recent conflicts in Iraq and Afghanistan. Improved pre-hospital survival, partly due to tourniquet use in controlling haemorrhage, means that secondary injury as the result of a dysregulated immune response to polytrauma is now a significant challenge. Multiple organ dysfunction syndrome (MODS) increases mortality 6-fold and quadruples the requirement for assistance in daily living at 2 years. Heterotopic ossification (HO) occurred in 65% of blast-related traumatic amputees, many of whom had tourniquets applied during care at point of wounding. This research sought to establish how blast exposure may potentiate the onset and effects of tourniquet-induced ischemia reperfusion injury (IRI) with the subsequent development of either local or systemic secondary injury. A pre-clinical study was performed in a rodent model to assess the effect of a 120 kPa systemic blast overpressure on the development of IRI following either 90 or 150 minutes of hind-limb tourniquet application. A further study was performed to assess the effect of tourniquet application in an established blast-associated lower extremity traumatic amputation model. Analysis of blood biomarkers and tissue gene expression was performed to assess changes in inflammatory mediators and signaling pathways, with microCT imaging to assess HO formation. Our results demonstrate that blast exposure following 150 minutes of tourniquet application increases markers of IRI and end organ injury through increased proinflammatory signaling. Tourniquets also increase proinflammatory signaling, oxidative stress and damage molecule signaling in a complex injured limb above that associated with traumatic amputation alone. This increases early remote organ dysfunction as well as increasing total bone formation at 12 weeks post-injury.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 05, 2019
- Accession Number
- AD1181543
Entities
People
- Philip J. Spreadborough
Organizations
- Uniformed Services University of the Health Sciences