Accession Number:

AD1050840

Title:

Interventional Vitamin C-A Strategy for Attenuation of Coagulopathy and Inflammation in Hemorrhagic Trauma and Shock

Descriptive Note:

Technical Report,30 Sep 2016,29 Sep 2017

Corporate Author:

Virginia Commonwealth University Richmond United States

Personal Author(s):

Report Date:

2017-10-01

Pagination or Media Count:

26.0

Abstract:

This is a novel study of high dose parenteral vitamin C VitC in a swine model of combined hemorrhagic shock and tissue trauma that simulates the course of a combat casualty by exhibiting the components of the lethal triad of acidosis, coagulopathy and hypothermia. The major goal of Year 2 of this project was to refine the treatment with intravenous VitC. In Phase 2, treatments were given immediately following injury at the start of resuscitation and at 2 hours post-resuscitation Resuscitation time 4h. In Phase 3, treatments were given immediately following injury at the start of resuscitation, at 2 and 4 hours post-resuscitation Resuscitation time 6h. Histological staining H and E of lungs from saline treated swine showed extensive hemorrhage, septal edema, protein leak and exuberant infiltration of inflammatory cells. Significant hemorrhage and cellular damage were also evident in liver and kidney sections. Treatment with VitC 200mgkg was associated with a lower degree of histological tissue injury and a significantly reduced ALI score. Treatment with VitC also reduced the expression of pro-inflammatory mediators in lungs, liver and kidneys. Preliminary lipidomic analysis showed that VitC at 200mgkg shifted the metabolic perturbation closer to the baseline indicating a net conservation of the circulating lipidome in the presence of VitC. Preliminary proteomic analysis revealed that VitC controls ADAMTS13 expression through unknown mechanisms and maintains an anti-coagulant phenotype in organ beds via the ADAMTS13-VWF axis. In sum, our data suggest that intravenous VitC at 200mgkg appears to significantly ameliorate the inflammatory status and trauma induced coagulopathy in this model.

Subject Categories:

  • Medicine and Medical Research
  • Biochemistry
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE