Thermal injury alters endothelial vasoconstrictor and vasodilator response to endotoxin.
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.
Murphy
J T
JT
Department of Surgery, University of Texas Southwestern Medical Center, Dallas 75235-9158, USA.
Duffy
S
S
Purdue
G F
GF
Hunt
J L
JL
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*
D019332:Endothelin-1; D004731:Endotoxins; D009569:Nitric Oxide; D011464:Epoprostenol