• Annals of surgery · Dec 2023

    Randomized Controlled Trial

    Omics Signatures of Tissue Injury and Hemorrhagic Shock in Swine.

    • Ian S LaCroix, Alexis Cralley, Ernest E Moore, Francesca I Cendali, Monika Dzieciatkowska, Patrick Hom, Sanchayita Mitra, Mitchell Cohen, Christopher Silliman, Angela Sauaia, Kirk C Hansen, and Angelo D'Alessandro.
    • Department of Biochemistry and Molecular Genetics, University of Colorado Denver-Anschutz Medical Campus, Aurora, CO.
    • Ann. Surg. 2023 Dec 1; 278 (6): e1299e1312e1299-e1312.

    ObjectiveAdvanced mass spectrometry methods were leveraged to analyze both proteomics and metabolomics signatures in plasma upon controlled tissue injury (TI) and hemorrhagic shock (HS)-isolated or combined-in a swine model, followed by correlation to viscoelastic measurements of coagulopathy via thrombelastography.BackgroundTI and HS cause distinct molecular changes in plasma in both animal models and trauma patients. However, the contribution to coagulopathy of trauma, the leading cause of preventable mortality in this patient population remains unclear. The recent development of a swine model for isolated or combined TI+HS facilitated the current study.MethodsMale swine (n=17) were randomized to either isolated or combined TI and HS. Coagulation status was analyzed by thrombelastography during the monitored time course. The plasma fractions of the blood draws (at baseline; end of shock; and at 30 minutes, 1, 2, and 4 hours after shock) were analyzed by mass spectrometry-based proteomics and metabolomics workflows.ResultsHS-isolated or combined with TI-caused the most severe omic alterations during the monitored time course. While isolated TI delayed the activation of coagulation cascades. Correlation to thrombelastography parameters of clot strength (maximum amplitude) and breakdown (LY30) revealed signatures of coagulopathy which were supported by analysis of gene ontology-enriched biological pathways.ConclusionThe current study provides a comprehensive characterization of proteomic and metabolomic alterations to combined or isolated TI and HS in a swine model and identifies early and late omics correlates to viscoelastic measurements in this system.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

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