Van De Wauwer Caroline, Neyrinck Arne P, Geudens Nele, Rega Filip R, Verleden Geert M, Verbeken Erik, Lerut Toni E, Van Raemdonck Dirk E M
Laboratory for Experimental Thoracic Surgery, University Hospital Gasthuisberg, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium.
Eur J Cardiothorac Surg. 2007 Jun;31(6):1125-32; discussion 1132-3. doi: 10.1016/j.ejcts.2007.01.070. Epub 2007 Mar 13.
The use of non-heart-beating donors (NHBD) has been propagated as an alternative to overcome the scarcity of pulmonary grafts. Formation of microthrombi after circulatory arrest, however, is a major concern for the development of reperfusion injury. We looked at the effect and the best route of pulmonary flush following topical cooling in NHBD.
Non-heparinized pigs were sacrificed by ventricular fibrillation and divided into three groups (n=6 per group). After 1h of in situ warm ischaemia and 2.5h of topical cooling, lungs in group I were retrieved unflushed (NF). In group II, lungs were explanted following an anterograde flush (AF) through the pulmonary artery with 50 ml/kg Perfadex (6 degrees C). Finally, in group III, lungs were retrieved after an identical but retrograde flush (RF) via the left atrium. Flush effluent was sampled at intervals to measure haemoglobin concentration. Performance of the left lung was assessed during 60 min in our ex vivo reperfusion model. Wet-to-dry weight ratio (W/D) of both lungs was calculated as an index of pulmonary oedema. IL-1beta and TNF-alpha protein levels in bronchial lavage fluid from both lungs were compared between groups.
Haemoglobin concentration (g/dl) was higher in the first effluent in RF versus AF (3.4+/-1.1 vs 0.6+/-0.1; p<0.05). Pulmonary vascular resistance (dynes x s x cm(-5)) was 975+/-85 RF versus 1567+/-98 AF and 1576+/-88 NF at 60 min of reperfusion (p<0.001). Oxygenation (mmHg) and compliance (ml/cmH(2)O) were higher (491+/-44 vs 472+/-61 and 430+/-33 NS, 22+/-3 vs 19+/-3 and 14+/-1 NS, respectively) and plateau airway pressure (cmH(2)O) was lower (11+/-1 vs 13+/-1 and 13+/-1 NS) after RF versus AF and NF, respectively. No differences in cytokine levels or in W/D ratios were observed between groups after reperfusion. Histology demonstrated microthrombi more often present after AF and NF compared to RF.
Retrograde flush of the lung following topical cooling in the NHBD results in a better washout of residual blood and microthrombi and subsequent reduced pulmonary vascular resistance upon reperfusion.
使用非心跳供体（NHBD）作为克服肺移植供体短缺的一种替代方法已得到推广。然而，循环停止后微血栓的形成是再灌注损伤发展的一个主要问题。我们研究了NHBD局部降温后肺灌洗的效果及最佳途径。
对未肝素化的猪进行室颤处死并分为三组（每组n = 6）。在原位温缺血1小时和局部降温2.5小时后，I组肺未灌洗即取出（NF）。II组肺通过肺动脉以50 ml/kg Perfadex（6℃）进行顺行灌洗（AF）后取出。最后，III组肺通过左心房进行相同的逆行灌洗（RF）后取出。每隔一段时间采集灌洗流出液以测量血红蛋白浓度。在我们的离体再灌注模型中评估左肺60分钟的功能。计算双肺的湿重与干重比（W/D）作为肺水肿的指标。比较三组双肺支气管灌洗液中IL-1β和TNF-α蛋白水平。
RF组首次流出液中的血红蛋白浓度（g/dl）高于AF组（3.4±1.1对0.6±0.1；p<0.05）。再灌注60分钟时，RF组的肺血管阻力（达因×秒×厘米-5）为975±85，AF组为1567±98，NF组为1576±88（p<0.001）。RF组的氧合（mmHg）和顺应性（ml/cmH2O）更高（分别为491±44对472±61和430±33，无显著差异；22±3对19±3和14±1，无显著差异），而RF组的平台气道压（cmH2O）低于AF组和NF组（分别为11±1对13±1和13±1，无显著差异）。再灌注后各组间细胞因子水平及W/D比值无差异。组织学显示，与RF组相比，AF组和NF组更常出现微血栓。
NHBD局部降温后肺的逆行灌洗能更好地清除残留血液和微血栓，进而降低再灌注时的肺血管阻力。
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