Evaluation of a protease inhibitor in the prevention of ischemia and reperfusion injury in hepatectomy under intermittent Pringle maneuver.
BACKGROUND
The severity of ischemia and reperfusion (I/R) injury is an important determinant of patient outcome in hepatic surgery. The aim of this study was to investigate the efficacy of a protease inhibitor in alleviating I/R injury to human liver in the setting of hepatectomy under intermittent Pringle maneuver.


METHODS
Sixty patients who underwent liver resection under conditions of intermittent inflow occlusion were randomly assigned to 2 groups (n = 30 each) according to the use of a synthetic protease inhibitor (gabexate mesilate or GM). GM was administered intravenously at a dosage of 2.0 mg/kg/h starting 12 hours before surgery until postoperative day 2. Preoperative and intraoperative clinical variables and postoperative outcomes were evaluated. The plasma levels of a cytokine, interleukin (IL)-6, as well as laboratory biochemical liver function parameters were analyzed to evaluate hepatic I/R injury.


RESULTS
The 2 groups of patients were comparable with regard to hepatic inflow occlusion time, extent of liver resection, and background liver histology. The preoperative administration of GM (GM group) substantially alleviated hepatic I/R injury compared with the untreated control group; postoperative serum transaminase levels were significantly decreased in association with marked suppression of IL-6 levels in blood circulation during surgery. This was accompanied by a lower incidence of postoperative complications. The patients without postoperative complications had significantly lower activities of plasma IL-6 at 24 hours after surgery.


CONCLUSIONS
This prospective randomized study demonstrated the hepatoprotective effect of a synthetic protease inhibitor in the setting of hepatectomy under the intermittent Pringle maneuver.
Kim
Yang-Il
YI
Department of Surgery, Kyungpook National University, School of Medicine, Daegu, Korea. yikim@knu.ac.kr
Chung
Han-Jun
HJ
Song
Kyung-Eun
KE
Hwang
Yoon-Jin
YJ
Lee
Jong-Won
JW
Lee
Yu-Jin
YJ
Chun
Byung-Yeol
BY
D000328:Adult; D005260:Female; D016670:Gabexate / Q000627:therapeutic use*; D006498:Hepatectomy / Q000009:adverse effects*; D006801:Humans; D007511:Ischemia / Q000517:prevention & control; D008099:Liver / Q000098:blood supply; D008107:Liver Diseases / Q000517:prevention & control* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D011446:Prospective Studies; D015427:Reperfusion Injury / Q000517:prevention & control*; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D014656:Vascular Surgical Procedures / Q000009:adverse effects*
D015842:Serine Proteinase Inhibitors; D016670:Gabexate