Takeyoshi I, Sunose Y, Iwazaki S, Tsutsumi H, Aiba M, Kasahara M, Ohwada S, Matsumoto K, Morishita Y
Second Department of Surgery, Gunma University School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
J Surg Res. 2001 Sep;100(1):25-31. doi: 10.1006/jsre.2001.6211.
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.
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.
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.
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.
普林格尔手术常用于肝脏手术，有时会导致肝衰竭。花生四烯酸的代谢产物由环氧化酶（Cox）转化，参与缺血再灌注损伤。本研究评估了选择性抑制Cox-2的FK 3311对犬肝切除术中缺血再灌注损伤的影响。
将动物分为四组，通过部分入流阻断进行60分钟的热缺血。FK治疗组（FK0.2：0.2mg/kg，FK1：1mg/kg，FK3：3mg/kg）接受FK3311，对照组接受赋形剂。再灌注后，切除非缺血叶并评估残余肝功能。
FK1组和FK3组，尤其是FK1组，组织血流量以及血清谷草转氨酶、谷丙转氨酶和乳酸脱氢酶水平均显著优于对照组。FK1组和FK3组的血栓素B2显著低于对照组。FK3组的6-酮-前列腺素F1α水平显著降低，FK1组相对不变。FK1组的组织学损伤较轻。FK1组的多形核中性粒细胞明显少于对照组。
FK3311可改善广泛肝切除术中普林格尔手术引起的缺血再灌注损伤。该药物在涉及血管隔离的扩大肝手术中可能具有临床应用价值。
