Impact of Immunopathy and Coagulopathy on Multi-Organ Failure and Mortality in a Lethal Porcine Model of Controlled and Uncontrolled Hemorrhage

Authors

Milomir O Simovic
James Bynum
Bin Liu
Jurandir J Dalle Lucca
Yansong Li

Language

English

Publication Date

2-21-2024

Journal

International Journal of Molecular Sciences

DOI

10.3390/ijms25052500

PMID

38473750

PMCID

PMC10931034

PubMedCentral® Posted Date

2-21-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Uncontrolled hemorrhage is a major preventable cause of death in patients with trauma. However, the majority of large animal models of hemorrhage have utilized controlled hemorrhage rather than uncontrolled hemorrhage to investigate the impact of immunopathy and coagulopathy on multi-organ failure (MOF) and mortality. This study evaluates these alterations in a severe porcine controlled and uncontrolled hemorrhagic shock (HS) model. Anesthetized female swine underwent controlled hemorrhage and uncontrolled hemorrhage by partial splenic resection followed with or without lactated Ringer solution (LR) or Voluven® resuscitation. Swine were surveyed 6 h after completion of splenic hemorrhage or until death. Blood chemistry, physiologic variables, systemic and tissue levels of complement proteins and cytokines, coagulation parameters, organ function, and damage were recorded and assessed. HS resulted in systemic and local complement activation, cytokine release, hypocoagulopathy, metabolic acidosis, MOF, and no animal survival. Resuscitation with LR and Voluven® after HS improved hemodynamic parameters (MAP and SI), metabolic acidosis, hyperkalemia, and survival but resulted in increased complement activation and worse coagulopathy. Compared with the LR group, the animals with hemorrhagic shock treated with Voluven® had worse dilutional anemia, coagulopathy, renal and hepatic dysfunction, increased myocardial complement activation and renal damage, and decreased survival rate. Hemorrhagic shock triggers early immunopathy and coagulopathy and appears associated with MOF and death. This study indicates that immunopathy and coagulopathy are therapeutic targets that may be addressed with a high-impact adjunctive treatment to conventional resuscitation.

Keywords

Humans, Female, Swine, Animals, Shock, Hemorrhagic, Blood Coagulation Disorders, Multiple Organ Failure, Hemorrhage, Cytokines, Acidosis, uncontrolled hemorrhagic shock, immunopathy, coagulopathy, MOF, mortality, swine, damage control resuscitation

Published Open-Access

yes

Recommended Citation

Simovic, Milomir O; Bynum, James; Liu, Bin; et al., "Impact of Immunopathy and Coagulopathy on Multi-Organ Failure and Mortality in a Lethal Porcine Model of Controlled and Uncontrolled Hemorrhage" (2024). Faculty, Staff and Student Publications. 6210.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6210