Hodyc Daniel, Hnilickova Olga, Hampl Vaclav, Herget Jan
Department of Physiology, Second Medical School, Charles University of Prague, Prague, Czech Republic.
J Heart Lung Transplant. 2008 Aug;27(8):890-7. doi: 10.1016/j.healun.2008.05.019. Epub 2008 Jul 3.
Lungs retrieved from non-heart-beating donors (NHBDs) may alleviate the shortage of suitable organs for transplantation. The critical point is the preservation of lungs during warm ischemia, when severe damage is caused by free radicals. We investigated the effect of ventilation, pre-arrest administration of heparin, and the cell-permeable free radical scavenger, tempol, on the function of NHBD grafts.
Six experimental and two control groups (n = 6 per group) were established. All experimental groups underwent a protocol of NHBD lung harvesting, which included 1 hour of warm ischemia after pentobarbital euthanasia followed by 90 minutes of cold ischemia. The groups were constructed as follows: Group An-non-ventilated during warm ischemia, no heparin; Group Av-room-air ventilated during warm ischemia, no heparin; Group Hn-non-ventilated, heparin added pre-arrest; Group Hv-ventilated, heparin; Group Tn-non-ventilated, heparin and tempol added pre-arrest; Group Tv-ventilated, tempol, heparin; Group Ac-control group, no warm and cold ischemia, lungs harvested immediately after euthanasia; and Group Tc-controls with tempol added pre-arrest. The lungs were then perfused ex vivo and the perfusion pressure, lung weight and arteriovenous difference in oxygen partial pressure were measured.
We found that room-air ventilation during warm ischemia caused severe pulmonary edema during reperfusion. Heparinization prevented an increase in perfusion pressure and ameliorated the oxygen transport ability. Pre-arrest administration of tempol prevented edema formation after ventilation during warm ischemia and had a positive effect on the oxygen transport ability of the lungs.
The free radical scavenger tempol, which has a very good ability to permeate biologic membranes, contributes to better preservation of lungs retrieved from NHBDs.
从非心脏跳动供体（NHBD）获取的肺脏可能缓解移植可用器官短缺的问题。关键在于在热缺血期间对肺脏的保存，此时自由基会造成严重损伤。我们研究了通气、心脏停搏前给予肝素以及细胞可渗透的自由基清除剂tempol对NHBD移植物功能的影响。
设立六个实验组和两个对照组（每组n = 6）。所有实验组均采用NHBD肺脏获取方案，包括在戊巴比妥安乐死后进行1小时热缺血，随后进行90分钟冷缺血。分组如下：An组 - 热缺血期间不通气，不使用肝素；Av组 - 热缺血期间用室内空气通气，不使用肝素；Hn组 - 不通气，心脏停搏前添加肝素；Hv组 - 通气，使用肝素；Tn组 - 不通气，心脏停搏前添加肝素和tempol；Tv组 - 通气，使用tempol和肝素；Ac组 - 对照组，无热缺血和冷缺血，安乐死后立即获取肺脏；Tc组 - 心脏停搏前添加tempol的对照组。然后对肺脏进行体外灌注，并测量灌注压力、肺重量以及氧分压的动静脉差值。
我们发现热缺血期间用室内空气通气会在再灌注期间导致严重肺水肿。肝素化可防止灌注压力升高并改善氧转运能力。心脏停搏前给予tempol可防止热缺血期间通气后水肿形成，并对肺脏的氧转运能力有积极影响。
具有良好生物膜渗透能力的自由基清除剂tempol有助于更好地保存从NHBD获取的肺脏。
