Citation

Bulger EM, Tower CM, Warner KJ, Garland T, Cuschieri J, Rizoli S, Rhind S, Junger WG. Med. Sci. Sports Exerc. 2011; 36(5): 435-439.

Affiliation

Department of Surgery, University of Washington*, Department of Surgery, University of Toronto**, Defence Research and Development Canada - Toronto***, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical SchoolΛ

Copyright

(Copyright © 2011, Lippincott Williams and Wilkins)

DOI

10.1097/SHK.0b013e318231ee2e

PMID

21841534

PMCID

PMC3204900

Abstract

Hypertonic saline (HS) has been investigated as an immune modulator following hemorrhagic shock and sepsis. The neutrophil (PMN) response to HS is regulated by the release of ATP, which is converted to adenosine and activates adenosine receptors. Binding to A3 adenosine receptors promotes PMN activation and inhibition of A3 receptors improves the efficacy of HS resuscitation. A3 receptor expression of PMN has not been previously evaluated in injured patients. METHODS:: Whole blood was obtained from 10 healthy volunteers and 60 injured patients within 2 hrs of injury. Inclusion criteria were blunt or penetrating injury with evidence of hypovolemic shock (SBP ≤ 90 mmHg and base deficit ≥6 mEq/L or need for blood transfusion); or evidence of severe traumatic brain injury (TBI) including initial Glasgow coma score (GCS) ≤ 8 or evidence of TBI on Head CT scan (Head AIS≥ 3) or intubation in the field or ED. A3 receptor expression was assessed by flow cytometry. PMN were also exposed to fMLP or HS (20-40 mM) in vitro. Clinical data was collected including admission physiology, injury severity (ISS scores), development of multiple organ failure, and survival. RESULTS:: In normal volunteers, < 1% of PMN expressed A3 receptors on the cell surface. A3 receptor expression was significantly higher in injured patients and the level of expression correlated with the severity of injury (ISS ≥ 25: A3 positive PMN 36.6% vs. ISS <25: 16.2%; p=0.019) and degree of hypovolemic shock (SBP≤ 90: A3 positive PMN 43.8% vs. SBP≤90: 20.6%; p=0.008). Stimulation with fMLP or HS increased A3 expression in normal volunteers, but only in patients with ISS< 25 or without hypovolemic shock. CONCLUSION:: A3 receptor expression on the surface of PMN is up-regulated by injury and increased expression levels are associated with greater injury severity and hypovolemic shock. Hypertonic saline increases A3 expression of PMN from healthy volunteers and less severely injured patients.

Language: en