Hamamoto I, Nemoto E M, Zhang S, Hartwell V R, Todo S
Department of Surgery, University of Pittsburgh, School of Medicine, PA 15261, USA.
Transpl Int. 1995;8(6):434-9. doi: 10.1007/BF00335594.
A reliable and easy method for assessing the viability of a cold ischemia-preserved donor liver prior to transplantation into the recepient is needed. Based on an earlier study, we hypothesized that liver free fatty acid (FFA) leakage into the preservation fluid may be a useful, atraumatic indicator of irreversible ischemic injury. The aim of the present study was to determine the time course and magnitude of liver FFA release into the preservation solution and its correlation with the duration of cold ischemic preservation compatible with survival after transplantation. Rat livers (n = 48) were flushed and preserved with University of Wisconsin (UW) solution at 4 degrees C for 0, 12, 24, and 48 h. Thereafter, half of the livers were analyzed for preservation fluid FFA (gas-liquid chromatography) and protein. The other half were perfused with Krebs-Henseleit (KH) solution at 37 degrees C for 1 h. Bile secretion and liver enzyme release (SGOT, SGPT, and LDH) were measured in addition to perfusate FFA and protein. Total FFA in the preservation fluid was 24 micrograms/g wet tissue after 12 h; it increased sharply 2.6-fold after 24 h and 3.7-fold after 48 h of preservation. Bile production was normal after 12 h of preservation but fell by 20% and 54% after 24 h and 48 h, respectively. LDH release rose from a value of 20 U/l at 0 time to 120 U/l and 260 U/l after 24 h and 48 h of preservation. These results suggest that liver viability declines sharply between 12 and 24 h of cold ischemic preservation, which corresponds with a sharp decrease in the 1-week survival from 100% to 33% after 12 h and 24 h, respectively, of cold ischemic preservation. We conclude that measuring FFA and LDH in the preservation solution of donor livers may be a useful means of assessing the quality of the cold-preserved liver before insertion into the recipient. We also speculate that a "threshold" FFA level in the UW preservation fluid indicating irreversible damage may be in the order of 35 micrograms total FFA/g liver. Studies on the clinical applicability of our findings are currently under way.
需要一种可靠且简便的方法，用于在将冷缺血保存的供体肝脏移植到受体之前评估其活力。基于早期的一项研究，我们推测肝脏游离脂肪酸（FFA）渗漏到保存液中可能是不可逆缺血损伤的一个有用的、无创伤的指标。本研究的目的是确定肝脏FFA释放到保存液中的时间进程和程度，以及其与移植后存活相容的冷缺血保存时间的相关性。将大鼠肝脏（n = 48）用威斯康星大学（UW）溶液在4℃冲洗并保存0、12、24和48小时。此后，一半的肝脏用于分析保存液中的FFA（气液色谱法）和蛋白质。另一半在37℃用克雷布斯-亨塞尔特（KH）溶液灌注1小时。除了测量灌注液中的FFA和蛋白质外，还测量胆汁分泌和肝酶释放（SGOT、SGPT和LDH）。保存12小时后，保存液中的总FFA为24微克/克湿组织；保存24小时后急剧增加2.6倍，保存48小时后增加3.7倍。保存12小时后胆汁生成正常，但保存24小时和48小时后分别下降20%和54%。LDH释放从0小时时的20 U/l增加到保存24小时和48小时后的120 U/l和260 U/l。这些结果表明，冷缺血保存12至24小时之间肝脏活力急剧下降，这与冷缺血保存12小时和24小时后1周存活率分别从100%急剧下降到33%相对应。我们得出结论，测量供体肝脏保存液中的FFA和LDH可能是在将肝脏植入受体之前评估冷保存肝脏质量的一种有用方法。我们还推测，UW保存液中表明不可逆损伤的“阈值”FFA水平可能约为35微克总FFA/克肝脏。目前正在对我们研究结果的临床适用性进行研究。
