Thermal injury alters endothelial vasoconstrictor and vasodilator responseto endotoxin

Background: The unique location of the endothelium makes it vulnerable to i njury from circulating factors created at remote wounds. In this study, we examined the effect of a sequential burn and lipopolysaccharide (LPS) chall enge on endothelial function in vitro, Methods: Human umbilical vein endothelial cells treated with 20% human seru m isolated from burn patients (>40% total burn surface area) at 2 and 24 ho urs postinjury. Cultures were subsequently treated with Escherichia coli LP S:0111:B4 (0.10-100 ng/mL). Endothelin-l (ET-1), 6-ketoPGF(1a), and NO2/NO3 were detected by using specific enzyme immunoassays, Results: Burn serum did not alter endothelial ET-1, PGI(2), or NO secretion compared with Control serum. LPS significantly enhanced 6-ketoPGF(1a) (54, 242 +/- 14,466 pg/10(6) cells) and NO2/NO3 (723 +/- 210 mu M) secretion, bu t 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-ketoPGF(1a) (16,509 +/- 3 ,785) and NO2/NO3 (354 +/- 98) responses to Burn/LPS were significantly dim inished compared with Control/LPS. Although this level of 6-ketoPGF(1a) was elevated compared with Control alone (7,518 +/- 2,299), NO2/NO3 was unchan ged (significance at p < 0.05). Conclusion: Thermal injury may prime remote endothelium and alter the respo nse to a septic focus with an enhanced vasoconstrictor (ET-1) and diminishe d vasodilator (PGI(2)/NO) response, a situation that may contribute to post burn distal organ injury.