title: Thermal injury alters endothelial vasoconstrictor and vasodilator response to endotoxin.
abstract: BACKGROUND
  The unique location of the endothelium makes it vulnerable to injury from circulating factors created at remote wounds. In this study, we examined the effect of a sequential burn and lipopolysaccharide (LPS) challenge on endothelial function in vitro.
  
  
  METHODS
  Human umbilical vein endothelial cells treated with 20% human serum isolated from burn patients (>40% total burn surface area) at 2 and 24 hours postinjury. Cultures were subsequently treated with Escherichia coli LPS:0111:B4 (0.10-100ng/mL). Endothelin-1 (ET-1), 6-ketoPGF1a, and NO2/NO3 were detected by using specific enzyme immunoassays.
  
  
  RESULTS
  Burn serum did not alter endothelial ET-1, PGI2, or NO secretion compared with Control serum. LPS significantly enhanced 6-ketoPGF1a (54,242+/-14,466 pg/10(6) cells) and NO2/ NO3 (723+/-210 microM) secretion, but not ET-1 compared with Control serum alone (3,878+/-963 and 219+/-110). Burn serum pretreatment significantly enhanced the ET-1 response to LPS (303+/-36 pg/10(6) cells vs. 193+/-47). The 6-ketoPGF1a (16,509+/-3,785) and NO2/NO3 (354+/-98) responses to Burn/LPS were significantly diminished compared with Control/LPS. Although this level of 6-ketoPGF1a was elevated compared with Control alone (7,518+/-2,299), NO2/NO3 was unchanged (significance at p < 0.05).
  
  
  CONCLUSIONS
  Thermal injury may prime remote endothelium and alter the response to a septic focus with an enhanced vasoconstrictor (ET-1) and diminished vasodilator (PGI2/NO) response, a situation that may contribute to postburn distal organ injury.
authors.affiliation: Department of Surgery, University of Texas Southwestern Medical Center, Dallas 75235-9158, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Murphy
authors.forename: S
authors.initials: S
authors.lastname: Duffy
authors.forename: G F
authors.initials: GF
authors.lastname: Purdue
authors.forename: J L
authors.initials: JL
authors.lastname: Hunt
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002056:Burns / Q000097:blood*; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004731:Endotoxins / Q000494:pharmacology*; D011464:Epoprostenol / Q000097:blood; D004926:Escherichia coli; D006801:Humans; D007124:Immunoenzyme Techniques; D009569:Nitric Oxide / Q000097:blood; D014471:Umbilical Veins; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D019332:Endothelin-1; D004731:Endotoxins; D009569:Nitric Oxide; D011464:Epoprostenol