Piratvisuth T, Dunne J B, Williams R, Tredger J M
Institute of Liver Studies, King's College Hospital, London, United Kingdom.
Transplantation. 1995 Jul 15;60(1):23-8. doi: 10.1097/00007890-199507150-00005.
Amlodipine, a long acting calcium antagonist, was used to reduce the adverse effects of ischemic/reperfusion injury studied in isolated perfused rat livers. Amlodipine (10 mumol/L) was added to University of Wisconsin (UW) solution in which the liver was stored for 24 hr at 4 degrees C and incorporated in the saline flush used to displace the UW solution before 20 min of warm ischemia (at 37 degrees C) and reperfusion. Initial median blood flow at 15 min was significantly higher after amlodipine treatment (2.78 vs. 1.41 ml/min/g of liver without amlodipine treatment, P = 0.013) as was the area under the curve of blood flow for the entire 3-hr perfusion (472 vs. 316 ml/g of liver, P = 0.003). Amlodipine treatment induced corresponding increases in oxygen delivery (1302 vs. 896 mumol of O2/g of liver over 3 hr of perfusion, P = 0.003) and oxygen consumption (279 vs. 242 mumol of O2/g of liver over 3 hr, P = 0.06). Initial bile flow at 15 min was increased 4-fold by amlodipine treatment (17.27 vs. 4.59 mg/hr/g of liver for sequential cold and warm ischemia, P = 0.013), and the median area under the curve of bile flow for the entire perfusion increased to 92.2 vs. 53.9 mg/g of liver (P = 0.0006). Amlodipine treatment also reduced glucose release into the perfusate (116 vs. 149 mmol/L/g of liver min over 3 hr, P = 0.03) and prevented hepatocyte injury by reducing alanine aminotransferase release both initially (0.43 vs. 0.96 IU/L/g of liver, P = 0.055) and overall (343 vs. 797 IU/L/g of liver min, P = 0.048). When amlodipine was added only to the UW solution, blood flow increased by 66% initially (P = 0.02) and 32% overall (P = 0.013), but there was no corresponding improvement in hepatic function. Amlodipine may reduce hepatic ischemic/reperfusion injury by cytoprotective effects on parenchymal and non-parenchymal hepatocytes during both preservation and reperfusion leading to an improvement in liver microcirculation and an inhibition of the release of toxic mediators.
氨氯地平是一种长效钙拮抗剂，用于减轻在离体灌注大鼠肝脏中研究的缺血/再灌注损伤的不良影响。将氨氯地平（10 μmol/L）添加到威斯康星大学（UW）溶液中，肝脏在4℃下于该溶液中保存24小时，并在37℃的温缺血20分钟和再灌注前用于置换UW溶液的生理盐水冲洗液中加入氨氯地平。氨氯地平治疗后，15分钟时的初始中位血流显著更高（2.78 vs. 未用氨氯地平治疗时的1.41 ml/min/g肝脏，P = 0.013），整个3小时灌注期间血流曲线下面积也更高（472 vs. 316 ml/g肝脏，P = 0.003）。氨氯地平治疗导致相应的氧输送增加（灌注3小时期间为1302 vs. 896 μmol O2/g肝脏，P = 0.003）和氧消耗增加（灌注3小时期间为279 vs. 242 μmol O2/g肝脏，P = 0.06）。氨氯地平治疗使15分钟时的初始胆汁流量增加了4倍（序贯冷缺血和温缺血时为17.27 vs. 4.59 mg/hr/g肝脏，P = 0.013），整个灌注期间胆汁流量曲线下的中位面积增加到92.2 vs. 53.9 mg/g肝脏（P = 0.0006）。氨氯地平治疗还减少了灌注液中葡萄糖的释放（3小时期间为116 vs. 149 mmol/L/g肝脏分钟，P = 0.03），并通过减少最初（0.43 vs. 0.96 IU/L/g肝脏，P = 0.055）和总体（343 vs. 797 IU/L/g肝脏分钟，P = 0.048）的丙氨酸转氨酶释放来预防肝细胞损伤。当仅将氨氯地平添加到UW溶液中时，血流最初增加了66%（P = 0.02），总体增加了32%（P = 0.013），但肝功能没有相应改善。氨氯地平可能通过在保存和再灌注期间对实质和非实质肝细胞的细胞保护作用来减轻肝脏缺血/再灌注损伤，从而改善肝脏微循环并抑制毒性介质的释放。
