Decreased Neutrophil Thromboxane A2 and Endothelial PGI2 Production in the Postoperative Period

Publisher Website
Google Scholar
Abstract
Severe trauma results in reversible abnormalities in neutrophil function, but the specific role in the pathogenesis of postoperative sepsis is undetermined. Twenty adult patients undergoing elective surgical procedures were studied. Blood samples were obtained prior to and 24 hours after operation. Blood neutro-phils were isolated and incubated (107 cells/mL) on bovine vascular endothelial cell monolayers. Untreated plasma or zymosan-activated plasma (ZAP) or 65 C inactivated plasma was added, and TxB2 and 6-keto PGF1α production measured after 2 hours. Endothelial damage was detected by light and scanning electron microscopy beginning 2 and 4 hours after treatment. Preoperatively, neutrophil TxB2 release was less than 200 pg/mL; following ZAP it was 2153 pg/mL (p < 0.001), with untreated plasma 1055 pg/mL (p < 0.005) and inactivated plasma 764 pg/mL (p < 0.01). Neutrophil TxB2 release on a plastic dish was not different from incubation on endothelium. Endothelial 6-keto PGF1α release following addition of untreated plasma preoperatively was 1308 pg/mL (p < 0.01), and with ZAP 1305 pg/mL (p < 0.01). Activated neutrophils did not alter 6-keto PGF1α production. Postoperatively, neutrophil TxB2 production in response to ZAP was 1092 pg/mL, which was significantly reduced compared to the preoperative response (p < 0.01). Endothelial damage by activated neutrophils in the postoperative period demonstrated on scanning electron microscopy was also reduced; 6-keto PGF1α release in the postoperative period inducted by ZAP was 569 pg/mL and by untreated plasma 549 pg/mL, which was significantly lower than in the preoperative period (p < 0.05 and p < 0.05, respectively). No difference in chemotaxis was demonstrated. It is concluded that operative trauma is followed by lowered neutrophil TxB2 release, appearance of a plasmatic factor that depresses endothelial 6-keto PGF1δ production, as well as decreased neutrophil-induced endothelial damage. The neutrophil-endothelial monolayer system is a sensitive method for detection of neutrophil and plasmatic dysfunction.