Systemic acylcarnitine levels are affected in response to multiple injuries and hemorrhagic shock: An analysis of lipidomic changes in a standardized porcine model

Abstract

Introduction Along with recent advances in analytical technologies, TCA-cycle intermediates are increasingly identified as promising makers for cellular ischemia and mitochondrial dysfunction during hemorrhagic shock (HS). For traumatized patients, the knowledge of the role of lipid oxidation substrates is sparse. In this study, we aimed to analyze the dynamics of systemic acylcarnitine (AcCa) release in a standardized polytrauma model with HS. Methods 52 male pigs (50 ± 5 kg) were randomized into two groups: Group IF (isolated fracture) was subject to a standardized femur shaft fracture. Group PT (polytrauma) was subject to a femur fracture, followed by blunt chest trauma, liver laceration and a pressure controlled hemorrhagic shock for 60 min. Resuscitation was performed with crystalloids. Fractures were stabilized by intramedullary nailing. Venous samples were collected at 6 timepoints (baseline, trauma, resuscitation, 2 h, 4 h and 6 h). Lipidomic analysis was performed via liquid chromatography coupled mass spectrometry. Measurements were collated with clinical markers and near-infrared spectrometry measurements (NIRS) of tissue perfusion. Longitudinal analyses were performed with linear mixed models and spearman’s correlations were calculated. A p-value of 0.05 was defined as threshold for statistical significance. Results From a total of 303 distinct lipids, we identified two species of long-chain AcCas. Both showed a highly significant (p < 0.001) two-fold increase after HS in Group PT that promptly normalized after resuscitation. This increase was associated with a significant decrease of the base excess (p = 0.005) but recovery after resuscitation was faster. For both AcCas, there were significant correlations with decreased muscle tissue oxygen delivery (p = 0.008, p = 0.003) and significant time-lagged correlations with the increase of creatine kinase (p < 0.001, p < 0.001). Conclusion Our results point to plasma AcCas as a possible indicator for mitochondrial dysfunction and cellular ischemia in HS. The more rapid normalization after resuscitation in comparison to acid base changes may warrant further investigation. Study Type Experimental Animal Model Level of Evidence N/A