The effect of a selective cyclooxygenase-2 inhibitor in extended liver resection with ischemia in dogs.
BACKGROUND
Pringle's procedure is commonly used during liver surgery, and it sometimes causes liver failure. Metabolites of arachidonic acid, which are converted by cyclooxygenase (Cox), are involved in ischemia-reperfusion injury. This study evaluated the effects of FK 3311, which selectively inhibits Cox-2, on ischemia-reperfusion injury during liver resection in dogs.


METHODS
The animals were divided into four groups and subjected to 60 min of warm ischemia by partial inflow occlusion. The FK-treated groups (FK0.2: 0.2 mg/kg, FK1: 1 mg/kg, FK3: 3mg/kg) received FK3311, and the control group received vehicle. Following reperfusion, the nonischemic lobes were resected and remnant liver function was evaluated.


RESULTS
Tissue blood flow and serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase were significantly better in the FK1 and FK3 groups, especially FK1, than in the control group. Thromboxane B(2) was significantly lower in the FK1 and FK3 groups than in the control group. The level of 6-keto-prostaglandin F(1alpha) was significantly lower in the FK3 group and relatively unchanged in the FK1 group. Histological damage was milder in the FK1 group. There were significantly fewer polymorphonuclear neutrophils in the FK1 group than in the control group.


CONCLUSIONS
FK3311 ameliorates the ischemia-reperfusion injury caused by Pringle's procedure during extensive liver resection. This agent may be clinically useful in extended liver surgery involving vascular isolation.
Takeyoshi
I
I
Second Department of Surgery, Gunma University School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
Sunose
Y
Y
Iwazaki
S
S
Tsutsumi
H
H
Aiba
M
M
Kasahara
M
M
Ohwada
S
S
Matsumoto
K
K
Morishita
Y
Y
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000410:Alanine Transaminase / Q000097:blood; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D051546:Cyclooxygenase 2; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000098:blood supply / Q000201:enzymology* / Q000601:surgery*; D008102:Liver Circulation; D017093:Liver Failure / Q000188:drug therapy / Q000473:pathology; D008297:Male; D011183:Postoperative Complications / Q000188:drug therapy / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D013929:Thromboxane B2 / Q000097:blood
D000813:Anilides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; C085566:FK 3311; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D007770:L-Lactate Dehydrogenase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase