Plasma Ameliorates Endothelial Dysfunction in Burn Injury

J Surg Res. 2019 Jan:233:459-466. doi: 10.1016/j.jss.2018.08.027. Epub 2018 Sep 22.

Abstract

Background: A complex inflammatory response mediates the systemic effects of burn shock. Disruption of the endothelial glycocalyx causes shedding of structural glycoproteins, primarily syndecan-1 (SDC-1), leading to endothelial dysfunction. These effects may be mitigated by resuscitative interventions.

Materials and methods: Sprague-Dawley rats were used to create small, medium, and large burns and uninjured controls. Three different intravenous resuscitation protocols were applied within each group: Lactated Ringer's (LR) alone, LR plus fresh frozen plasma (FFP), or LR plus albumin. Blood was serially collected, and plasma SDC-1 was quantified with enzyme-linked immunosorbent assay. In one cohort, Evan's Blue Dye (EBD) was administered and quantified in lung by spectrophotometry as a functional assay of vascular permeability. In a second cohort, intact SCD-1 was quantified by immunohistochemistry in lung tissue. Statistical analysis employed two-way analysis of variance with multiple comparisons and Student's t-test.

Results: EBD extraction from lung was significantly greater with higher injury severity versus controls. Extraction decreased significantly in large-burn animals with addition of FFP to LR versus LR-only; addition of albumin to LR did not decrease EBD extraction. Plasma SCD-1 increased in injured animals compared with controls, and changes correlated with injury severity in all resuscitation groups (significance, P < 0.05). Lung SCD-1 staining reflected the results in the EBD assay.

Conclusions: Addition of FFP, not of albumin, to post-burn resuscitation diminishes vascular leakage associated with large burns. Addition of colloid does not affect SDC-1 shedding as measured in plasma. Ongoing work will further define pathophysiologic mechanisms and potential therapeutic interventions to mitigate injury and promote repair of the endothelial glycocalyx.

Keywords: Albumin; Burn; Endothelial dysfunction; Glycocalyx; Plasma; Syndecan-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Component Transfusion / methods*
  • Burns / complications
  • Burns / diagnosis
  • Burns / therapy*
  • Disease Models, Animal
  • Endothelial Cells / cytology
  • Endothelial Cells / pathology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / pathology
  • Glycocalyx / pathology
  • Humans
  • Injury Severity Score
  • Lung / blood supply
  • Lung / pathology
  • Male
  • Plasma*
  • Rats
  • Rats, Sprague-Dawley
  • Resuscitation / methods*
  • Ringer's Lactate / administration & dosage
  • Syndecan-1 / metabolism
  • Treatment Outcome
  • Vascular Diseases / etiology
  • Vascular Diseases / pathology
  • Vascular Diseases / therapy*

Substances

  • Ringer's Lactate
  • Sdc1 protein, rat
  • Syndecan-1