Department of Cardiothoracic Surgery, Heart Center, University Hospital of Cologne, Cologne, Germany.
J Heart Lung Transplant. 2013 Mar;32(3):355-9. doi: 10.1016/j.healun.2012.11.025. Epub 2013 Jan 10.
Non-heart-beating donor (NHBD) utilization can significantly increase the limited donor lung pool. However, optimal preservation of organ function is crucial as the development of ischemia/reperfusion injury (IRI) can result in severe surfactant inactivation. Exogenic surfactant application is effective in prevention and therapy of IRI. Studies on optimal timing of Curosurf, including application in NHBDs, have not been done, but could help to optimize NHBD lung transplantation.
The extracorporeal screening model (ESM) included rat lungs (Sprague-Dawley, n = 5/group) preserved with Perfadex. In 3 test groups, Curosurf was administered before flush preservation (T1), after 4-hour ischemia (T2) or during reperfusion (T3). Results after extracorporeal reperfusion were compared with controls. The transplantation model (TM) consisted of asystolic pigs (n = 5/group) ventilated for 7 hours with warm ischemia (WIT, Groups 1 and 2). In Group 2, 100 mg/kg BW Curosurf was bronchoscopically administered before preservation. After 3-hour cold storage, left lung transplantation was performed and data were compared with sham control data (Group 3).
For the ESM, T1 lung oxygenation (SurfT1 167±47.4 mm Hg) was superior to others (SurfT2 47.3±15.3 mm Hg, SurfT3 77.2±48.8 mm Hg, controls 65.5±46.2 mm Hg; p<0.02). Stereology demonstrated poorer intra-alveolar edema formation in controls (1.86±2.53% of parenchyma) compared with surfactant-treated lungs (<0.02% of parenchyma) (p<0.02). Intra-alveolar erythrocyte sequestration as an indicator of vascular leakage was significantly lower in T1 lungs (0.15±0.12% of parenchyma) compared with all other groups (>0.74% of parenchyma). For TM, mortality was 80% in the untreated group and 100% in the Curosurf group, suggesting that a 7-hour WIT is above the limit for NHBD utilization.
Donor lung pre-treatment with endobronchial pre-preservation Curosurf offers optimal preservation quality when compared with post-ischemic application or during reperfusion and results in improved functional outcome when compared with controls. Expensive NHBD pre-treatment with Curosurf cannot improve poor allograft outcome after extended WIT and should therefore not be considered. Seven-hour WIT seems generally to be above the limits for use in NHBD lung donors.
非心脏死亡供体（NHBD）的利用可以显著增加有限的供肺池。然而，器官功能的最佳保存至关重要，因为缺血/再灌注损伤（IRI）的发展会导致严重的表面活性剂失活。外源性表面活性剂的应用在预防和治疗 IRI 方面是有效的。关于 Curosurf 的最佳时机的研究，包括在 NHBD 中的应用，尚未进行，但可能有助于优化 NHBD 肺移植。
体外筛选模型（ESM）包括用 Perfadex 保存的大鼠肺（Sprague-Dawley，每组 5 只）。在 3 个实验组中，Curosurf 在冲洗保存前（T1）、4 小时缺血后（T2）或再灌注期间（T3）给药。比较体外再灌注后的结果与对照组。移植模型（TM）由接受 7 小时温缺血（WIT，组 1 和 2）的心脏停搏猪组成（每组 5 只）。在组 2 中，100mg/kg BW Curosurf 在保存前经支气管镜给药。在 3 小时冷藏后，进行左肺移植，并将数据与假手术对照数据（组 3）进行比较。
对于 ESM，T1 肺氧合（SurfT1 167±47.4mm Hg）优于其他组（SurfT2 47.3±15.3mm Hg、SurfT3 77.2±48.8mm Hg、对照组 65.5±46.2mm Hg；p<0.02）。体视学显示，与表面活性剂处理的肺相比，对照组（肺实质的 1.86±2.53%）肺泡内水肿形成更差（<0.02%的肺实质）（p<0.02）。作为血管渗漏指标的肺泡内红细胞扣留，T1 肺明显低于其他组（肺实质的 0.15±0.12%）（>0.74%的肺实质）。对于 TM，未治疗组的死亡率为 80%，Curosurf 组为 100%，表明 7 小时 WIT 超过了 NHBD 利用的极限。
与缺血后应用或再灌注期间相比，供体肺支气管内预保存前用 Curosurf 预处理可提供最佳保存质量，并与对照组相比可改善功能结果。昂贵的 NHBD 预处理用 Curosurf 不能改善延长 WIT 后的移植物不良结局，因此不应考虑。7 小时 WIT 似乎通常超过 NHBD 肺供体的使用极限。
