Takahashi K, Hakamada K, Totsuka E, Umehara Y, Sasaki M
Second Department of Surgery, Hirosaki University School of Medicine, Japan.
Transplantation. 2000 May 27;69(10):2028-34. doi: 10.1097/00007890-200005270-00009.
Fatty liver is associated with primary nonfunction after liver transplantation, contributing a shortage of suitable liver grafts. Because extensive investigation of mechanisms underlying such nonfunction has been limited largely to rodents, we made a new fatty liver model in dogs and studied primary nonfunction after warm ischemia.
We developed a diet rich in fat but deficient in choline to induce fatty change in canine liver and investigated effects of 60 min of warm ischemia and reperfusion in dogs with such fatty livers.
Microscopically evident steatosis increased with duration of dietary manipulation (up to 12 weeks), as did hepatic total lipid and triglyceride levels. No dog with >30% of steatotic hepatocytes, >445 mg/g hepatic total lipid or >145 mg/g hepatic triglyceride survived after 60 min of warm ischemia. Arterial ketone body ratios decreased and blood endotoxin increased after reperfusion in nonsurvivors. The main histologic finding in livers of nonsurvivors was marked sinusoidal congestion.
Damage to hepatocytes and nonparenchymal cells after warm ischemia and reperfusion was thought to be closely related to sinusoidal microcirculatory disturbances in fatty livers. The canine fatty liver model reported here may be useful in studying the pathology of primary nonfunction and in establishing criteria for allowable degrees of fatty change in potential liver grafts.
脂肪肝与肝移植后的原发性无功能相关，导致合适肝移植物短缺。由于对这种无功能潜在机制的广泛研究在很大程度上局限于啮齿动物，我们建立了一种犬类脂肪肝模型，并研究了热缺血后的原发性无功能。
我们开发了一种高脂肪但胆碱缺乏的饮食来诱导犬肝脏脂肪变性，并研究了热缺血60分钟及再灌注对患有此类脂肪肝的犬的影响。
显微镜下明显的脂肪变性随着饮食控制时间（长达12周）的延长而增加，肝脏总脂质和甘油三酯水平也是如此。热缺血60分钟后，没有一只肝细胞脂肪变性>30%、肝脏总脂质>445mg/g或肝脏甘油三酯>145mg/g的犬存活下来。非存活犬再灌注后动脉酮体比值降低，血液内毒素增加。非存活犬肝脏的主要组织学发现是明显的窦性充血。
热缺血和再灌注后肝细胞和非实质细胞的损伤被认为与脂肪肝中的窦性微循环障碍密切相关。本文报道的犬脂肪肝模型可能有助于研究原发性无功能的病理，并有助于建立潜在肝移植物允许脂肪变性程度的标准。
