Institute for Laboratory Animal Science and Experimental Surgery, RWTH Aachen University, Aachen, Germany.
Liver Transpl. 2012 Feb;18(2):219-25. doi: 10.1002/lt.22442.
The increasing shortage of donor organs has led to the increasing use of organs from non-heart-beating donors. We aimed to assess the impact of venous systemic oxygen persufflation (VSOP) supplemented with nitric oxide (NO) gas during the cold storage (CS) of warm ischemia (WI)-damaged experimental liver grafts. Rat livers (n = 5 per group) were retrieved after 30 minutes of WI induced by cardiac arrest (the WI group) and were thereafter preserved for 24 hours by CS in histidine tryptophan ketoglutarate solution. During CS, gaseous oxygen was insufflated via the caval vein with 40 ppm NO (the VSOP-NO group) or without NO (the VSOP group). Cold-stored livers without WI served as controls. Liver viability was assessed after the preservation period by normothermic isolated reperfusion for 45 minutes with oxygenated Krebs-Henseleit buffer. After 45 minutes of reperfusion, the VSOP-NO-treated livers showed significantly lower alanine aminotransferase values than the WI-damaged livers (10.2 ± 0.2 versus 78.2 ± 14.6 IU/L), whereas the control livers showed no differences from the VSOP-NO-treated livers. The mitochondrial enzyme release was lower in the VSOP-NO group (4.0 ± 0.7 IU/L) versus the WI group (18.2 ± 4.9 IU/L). An increased portal vein pressure was observed throughout reperfusion (45 minutes) in the WI group (21.7 ± 0.2 mm Hg) versus the VSOP-NO group (12.2 ± 0.8 mm Hg) and the control group (19.9 ± 0.4 mm Hg). Furthermore, the NO concentration in the perfusate after 5 minutes of reperfusion was highest in the VSOP-NO group. The release of malondialdehyde into the perfusate was significantly reduced in the VSOP-NO group (0.9 ± 0.1 nmol/mL) versus the WI group (31.3 ± 5.3 nmol/mL). In conclusion, the resuscitation of livers after 30 minutes of WI to a level comparable to that of nonischemically damaged livers is possible with VSOP supplemented with NO gas. Moreover, the application of VSOP with NO minimizes the extent of injuries caused by oxygen free radicals during preservation.
越来越多的捐赠器官短缺导致越来越多的人使用非心跳供体的器官。本研究旨在评估静脉全身氧灌输（VSOP）联合一氧化氮（NO）气体在温缺血（WI）损伤实验性肝移植物冷藏（CS）期间的影响。心脏骤停后 30 分钟，每组 5 只大鼠（n=5）的 WI 导致 WI （WI 组），此后通过组氨酸色氨酸酮戊二酸溶液 CS 保存 24 小时。CS 期间，通过腔静脉向 40 ppm NO （VSOP-NO 组）或不添加 NO （VSOP 组）吹入气态氧。无 WI 的冷藏肝脏作为对照。保存期后，通过充氧 Krebs-Henseleit 缓冲液进行 45 分钟的常温隔离再灌注来评估肝存活率。再灌注 45 分钟后，与 WI 损伤的肝脏相比，VSOP-NO 处理的肝脏的丙氨酸转氨酶值显著降低（10.2±0.2 比 78.2±14.6 IU/L），而对照肝脏与 VSOP-NO 处理的肝脏没有差异。VSOP-NO 组的线粒体酶释放较低（4.0±0.7 IU/L）与 WI 组（18.2±4.9 IU/L）相比。WI 组在整个再灌注（45 分钟）过程中门静脉压力升高（21.7±0.2 mmHg）与 VSOP-NO 组（12.2±0.8 mmHg）和对照组（19.9±0.4 mmHg）相比。此外，再灌注 5 分钟后，VSOP-NO 组灌流液中的 NO 浓度最高。VSOP-NO 组丙二醛向灌流液中的释放明显减少（0.9±0.1 nmol/mL）与 WI 组（31.3±5.3 nmol/mL）相比。总之，用 NO 气体补充的 VSOP 使 30 分钟 WI 后的肝脏复苏达到与非缺血性损伤肝脏相当的水平是可能的。此外，应用含有 NO 的 VSOP 可最大限度地减少保存期间氧自由基引起的损伤程度。
