Zhai Wei, Jungraithmayr Wolfgang, De Meester Ingrid, Inci Ilhan, Augustyns Koen, Arni Stephan, Hillinger Sven, Scharpé Simon, Weder Walter, Korom Stephan
Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
Transplantation. 2009 Apr 27;87(8):1140-6. doi: 10.1097/TP.0b013e31819e04c3.
Enzymatic activity inhibition of CD26/dipeptidylpeptidase IV (CD26/DPP IV) attenuated short-term post-Tx (transplantation) ischemia-reperfusion injury after 18-hr-ischemia. Here, we investigated the effect of intragraft CD26/DPP IV catalytic inhibition on primary graft dysfunction during 7 day post-Tx, following extended ischemia.
A syngeneic rat (LEW [Lewis abstract]) orthotopic lung Tx model was used, grafts exposed to 18 hr cold ischemia before Tx. Controls were flushed and preserved in Perfadex, and harvested after 1 day (CON1) or 7 day (CON7) post-Tx. Investigational groups IN1, IN3, and IN7 grafts were perfused with and stored in Perfadex + inhibitor (AB192) and harvested at 1, 3, and 7 days post-Tx, respectively. Blood gas analysis, peak airway pressure (PAwP), wet/dry weight ratio, myeloperoxidase thiobarbituric acid reactive substances (TBARS), and staining for vasoactive intestinal peptide (VIP) were analyzed.
IN1 versus CON1 showed preserved histology, increased pO2 (P<0.01), lowered PAwP (P<0.01), less edema (P<0.05) and decreased TBARS (P<0.05). Survival was better for IN7 versus CON7 (P<0.01). The course of AB192-perfused grafts from 1 to 7 days displayed improved values for pO2 (P<0.01), PAwP (P<0.01), edema (P<0.05), TBARS (P<0.05), and myeloperoxidase (P<0.05). Compared with controls, VIP was preserved during 18 hr ischemia in alveolar macrophages (P=0.0001) and respiratory epithelial cells (P=0.001).
Perfusion with an inhibitor of CD26/DPP IV enzymatic activity significantly reduced the incidence and severity of pulmonary primary graft dysfunction and enabled recovery after extended ischemia. This is the first report that CD26/DPPIV inhibitor treatment increases local pulmonary VIP levels, which correlate with preserved ventilatory function and pulmonary structural integrity.
CD26/二肽基肽酶IV（CD26/DPP IV）的酶活性抑制可减轻移植后18小时缺血后的短期移植后缺血再灌注损伤。在此，我们研究了在长时间缺血后，移植内CD26/DPP IV催化抑制对移植后7天内原发性移植功能障碍的影响。
使用同基因大鼠（LEW[刘易斯摘要]）原位肺移植模型，移植前将移植物暴露于18小时冷缺血。对照组用Perfadex冲洗并保存，在移植后1天（CON1）或7天（CON7）收获。研究组IN1、IN3和IN7的移植物用Perfadex+抑制剂（AB192）灌注并保存，分别在移植后1、3和7天收获。分析血气分析、气道峰值压力（PAwP）、湿/干重比、髓过氧化物酶硫代巴比妥酸反应物质（TBARS）以及血管活性肠肽（VIP）染色。
IN1与CON1相比，组织学保存良好，pO2升高（P<0.01），PAwP降低（P<0.01），水肿减轻（P<0.05），TBARS降低（P<0.05）。IN7与CON7相比生存率更高（P<0.01）。从1天到7天，AB192灌注的移植物在pO2（P<0.01）、PAwP（P<0.01）、水肿（P<0.05）、TBARS（P<0.05）和髓过氧化物酶（P<0.05）方面的值有所改善。与对照组相比，在18小时缺血期间，肺泡巨噬细胞（P=0.0001）和呼吸上皮细胞（P=0.001）中的VIP得以保留。
用CD26/DPP IV酶活性抑制剂灌注可显著降低肺原发性移植功能障碍的发生率和严重程度，并使长时间缺血后得以恢复。这是第一份关于CD26/DPPIV抑制剂治疗可提高局部肺VIP水平的报告，这与保留通气功能和肺结构完整性相关。
