Sunose Y, Ohwada S, Takeyoshi I, Matsumoto K, Tsutsumi H, Tomizawa N, Kawate S, Morishita Y
Second Department of Surgery, Gunma University Faculty of Medicine, Maebashi, Japan.
Surgery. 2001 Nov;130(5):819-25. doi: 10.1067/msy.2001.116928.
This study investigated the possibility of pharmacologic protection using an endothelin (ET) receptor antagonist, TAK-044 (TAK), for small bowel autograft in a canine controlled non-heart-beating donor (NHBD) model.
Sixteen adult mongrel dogs were allocated into 2 groups. TAK (3 mg/kg) (n = 8) was administered intravenously 30 minutes before ischemia and 30 minutes before graft reperfusion. Vehicle was administered in the control (n = 8). The superior mesenteric artery and vein were clamped for 90 minutes to induce warm ischemia as a controlled NHBD model. The entire small bowel then was harvested and stored in 4 degrees C University of Wisconsin solution for 4 hours. The autograft was transplanted orthotopically. Mucosal tissue blood flow, intramucosal pH (pHi), and serum ET-1 levels were measured. Specimens were evaluated histopathologically and ET-1 immunohistochemically.
TAK provided significantly higher tissue blood flow and pHi at 3 and 6 hours after graft reperfusion and significantly higher serum ET-1 levels at 1 hour after graft reperfusion as compared with the control group. TAK had histopathologic tissue damage graded as superficial, did not reach to grade 5 on Park's grading as in controls, and provided less intense immunoreactivity for ET-1 immunohistochemical staining.
TAK may have clinical application in small bowel transplantation from controlled NHBD or conditions related to ischemia-reperfusion (I/R) injury.
本研究在犬类控制性非心跳供体（NHBD）模型中，探究了使用内皮素（ET）受体拮抗剂TAK-044（TAK）对小肠自体移植进行药物保护的可能性。
将16只成年杂种犬分为2组。TAK组（3mg/kg）（n = 8）在缺血前30分钟和移植器官再灌注前30分钟静脉给药。对照组（n = 8）给予赋形剂。夹闭肠系膜上动脉和静脉90分钟以诱导热缺血，作为控制性NHBD模型。然后切取整个小肠，保存在4℃的威斯康星大学溶液中4小时。将自体移植器官原位移植。测量黏膜组织血流量、黏膜内pH值（pHi）和血清ET-1水平。对标本进行组织病理学和ET-1免疫组织化学评估。
与对照组相比，TAK组在移植器官再灌注后3小时和6小时时组织血流量和pHi显著更高，在移植器官再灌注后1小时时血清ET-1水平显著更高。TAK组组织病理学损伤分级为浅表性，不像对照组那样达到帕克分级的5级，并且ET-1免疫组织化学染色的免疫反应性较弱。
TAK可能在控制性NHBD小肠移植或与缺血再灌注（I/R）损伤相关的情况下具有临床应用价值。
