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

Autor: Kalbas Y; From the Department of Trauma Surgery (Y. Kalbas, F.K.-L., S.H., M.P.J.T., R.P., P.C., H.-C.P.), University Hospital Zurich, Harald-Tscherne Laboratory for Orthopaedic and Trauma Research (Y. Kalbas, Y. Kumabe, F.K.-L., S.H., M.P.J.T., S.M., C.H., R.P., P.C., H.-C.P.), Center for Preclinical Development (M.W.), University Hospital of Zurich, University of Zurich; Department of Health Sciences and Technology (N.C.), Swiss Federal Institute of Technology; Institute of Clinical Chemistry (A.J.H., T.H.), University Hospital Zurich, University of Zurich, Zurich, Switzerland; and Department of Orthopaedic Trauma and Reconstructive Surgery (F.H.), University Hospital RWTH, Aachen, Germany., Kumabe Y, Karl-Ludwig F, Halvachizadeh S, Teuben MPJ, Weisskopf M, Cesarovic N, Hülsmeier AJ, Märsmann S, Hierholzer C, Hildebrand F, Hornemann T, Pfeifer R, Cinelli P, Pape HC
Jazyk: angličtina
Zdroj: The journal of trauma and acute care surgery [J Trauma Acute Care Surg] 2024 Aug 01; Vol. 97 (2), pp. 248-257. Date of Electronic Publication: 2024 Mar 29.
DOI: 10.1097/TA.0000000000004328
Abstrakt: Introduction: Along with recent advances in analytical technologies, tricarboxylic acid-cycle intermediates are increasingly identified as promising makers for cellular ischemia and mitochondrial dysfunction during hemorrhagic shock. 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 hemorrhagic shock.
Methods: Fifty-two male pigs (50 ± 5 kg) were randomized into two groups: group isolated fracture was subject to a standardized femur shaft fracture, and group polytrauma was subject to a femur fracture, followed by blunt chest trauma, liver laceration, and a pressure-controlled hemorrhagic shock for 60 minutes. Resuscitation was performed with crystalloids. Fractures were stabilized by intramedullary nailing. Venous samples were collected at six time points (baseline, trauma, resuscitation, 2 hours, 4 hours, and 6 hours). Lipidomic analysis was performed via liquid chromatography coupled mass spectrometry. Measurements were collated with clinical markers and near-infrared spectrometry measurements 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) twofold increase after hemorrhagic shock in group polytrauma 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 hemorrhagic shock. The more rapid normalization after resuscitation in comparison with acid base changes may warrant further investigation.
(Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Surgery of Trauma.)
Databáze: MEDLINE