Dunne J B, Davenport M, Williams R, Tredger J M
Institute of Liver Studies, King's College Hospital, London, United Kingdom.
Transplantation. 1994 Apr 27;57(8):1161-8. doi: 10.1097/00007890-199404270-00004.
S-Adenosylmethionine (SAMe) and N-acetylcysteine (NAC), two agents with known benefit for reducing hepatic injury, were used to treat ischemic injury in a rat liver perfusion model. We compared cold ischemic injury with sequential periods of cold and warm ischemia that equate to episodes during the storage and implantation of liver grafts. The additional period of 20 min warm ischemia after 24 hr cold ischemia profoundly impaired initial (15 min) mean blood flow (1.8 +/- 0.1 vs. 2.7 +/- 0.4 ml/min/g liver for cold ischemia, P < 0.001) and bile flow (2.31 +/- 0.74 vs. 10.6 +/- 3.96 mg/hr/g liver for cold ischemia, P < 0.001) and increased the oxygen extraction ratio (OER) (0.53 +/- 0.03 vs. 0.29 +/- 0.08 for cold ischemia, P < 0.01) and acid release from glycolysis (0.18 +/- 0.02 vs. 0.11 +/- 0.02 mmol/g liver for cold ischemia, P < 0.05). Impairment of blood flow, bile flow, and OER was sustained throughout the 3-hr perfusion. In the same model, SAMe restored hepatic blood flow to control values when administered to the donor, included in the UW, and added as a bolus to the perfusate on reperfusion. SAMe also improved OER (P < 0.001 vs. sequential cold and warm ischemia) and initial bile flow (9.63 +/- 2.01 mg/hr/g liver, P < 0.01), returning values to control levels by 3 hr. SAMe reduced the initial release of glucose upon reperfusion (P < 0.01) and improved subsequent glucose uptake, but corresponding benefits on enzyme release from damaged hepatocytes (AST) or endothelial cells (purine nucleoside phosphorylase) were not observed. Equimolar concentrations of NAC induced transitory improvements in blood and bile flow but these were not sustained beyond 30 min of reperfusion.
S-腺苷甲硫氨酸（SAMe）和N-乙酰半胱氨酸（NAC）是两种已知对减轻肝损伤有益的药物，在大鼠肝脏灌注模型中用于治疗缺血性损伤。我们将冷缺血损伤与等同于肝移植保存和植入过程中发作的连续冷缺血和温缺血期进行了比较。24小时冷缺血后额外20分钟的温缺血严重损害了初始（15分钟）平均血流（冷缺血时为1.8±0.1 vs. 2.7±0.4 ml/min/g肝脏，P<0.001）和胆汁流量（冷缺血时为2.31±0.74 vs. 10.6±3.96 mg/hr/g肝脏，P<0.001），并增加了氧摄取率（OER）（冷缺血时为0.53±0.03 vs. 0.29±0.08，P<0.01）和糖酵解产生的酸释放（冷缺血时为0.18±0.02 vs. 0.11±0.02 mmol/g肝脏，P<0.05）。在整个3小时灌注过程中，血流、胆汁流量和OER的损害持续存在。在同一模型中，当将SAMe给予供体、包含在UW中并在再灌注时作为推注添加到灌注液中时，可将肝血流恢复到对照值。SAMe还改善了OER（与连续冷缺血和温缺血相比，P<0.001）和初始胆汁流量（9.63±2.01 mg/hr/g肝脏，P<0.01），到3小时时将数值恢复到对照水平。SAMe减少了再灌注时葡萄糖的初始释放（P<0.01）并改善了随后的葡萄糖摄取，但未观察到对受损肝细胞（AST）或内皮细胞（嘌呤核苷磷酸化酶）释放酶的相应益处。等摩尔浓度的NAC可使血流和胆汁流量出现短暂改善，但在再灌注30分钟后这些改善未持续。
