Characterization of lipidome alterations in a standardized porcine model with multiple trauma and hemorrhagic shock: Are they driven by hepatic injury?

Abstract

Recent advances in analytic technology enable the investigation the response to severe injury and hemorrhagic shock (HS) can be characterized on a molecular level. While metabolomic and proteomic approaches are being actively applied in trauma research, lipidomics are less well explored. Fifty-two male pigs were randomized to two conditions: Group PT (polytrauma) with blunt chest trauma, liver laceration, femoral fracture, and a 60-minute pressure-controlled HS and Group IF with an isolated femur fracture. Venous samples were taken from six time points (baseline, trauma, resuscitation, 2 hours, 4 hours, and 6 hours). Lipidomic analyses were performed using liquid chromatography coupled mass spectrometry. Findings were collated with standard clinical markers and near-infrared spectrometry measurements for organ perfusion. We identified 303 distinct lipid species that were organized in 17 functional classes. Significant group differences in lipidome dynamics were identified for the majority of lipid classes. Most notably, lipid classes involved in lipoprotein synthesis showed significant reduction over time in Group PT only. These findings collated with a significant decrease of liver perfusion during HS and a significant (~20-fold) increase of transaminases. Polytrauma with HS induces a global decrease of the circulating lipidome through acute (ischemic and mechanical) liver injury, leading to a disruption of lipoprotein synthesis. This decrease might be of clinical significance for multiply injured patients in a posttraumatic energy-depleted state and collation with clinical data, and global metabolomic analyses should be performed.