Repetitive Gastric Aspiration Leads to Augmented Indirect Allorecognition After Lung Transplantation in Miniature Swine
Repetitive Gastric Aspiration Leads to Augmented Indirect Allorecognition After Lung Transplantation in Miniature Swine
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DOI：
10.1097/tp.0b013e318190afe6
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发表时间：
2008-12-27
期刊：
影响因子：
6.2
通讯作者：
Allan, James S.
中科院分区：
文献类型：
--
作者：
Meltzer, Andrew J.;Weiss, Matthew J.;Allan, James S.
导论.有胃食管反流病（GERD）记录的肺移植受者发生移植物功能障碍的风险增加。在这里，我们提出了第一个大动物模型的胃吸入后异基因肺移植和一些初步的数据表明，慢性吸入的影响的直接和间接途径的异基因肺移植。在主要组织相容性复合体I类差异的小型猪中进行左原位肺移植（n=3），随后给予12天高剂量环孢素A。在移植时，将经气管导管放置在隆突处，支气管吻合口上方。放置胃造口管，每日抽吸胃内容物。随后，每天用胃吸出物（3 mL/hr X 8 hr/天）滴注移植肺，持续50天。接受者每天进行全血细胞计数，定期胸片和活检。进行了体外研究，包括细胞介导的淋巴细胞溶解、混合淋巴细胞反应和肽增殖试验。结果从这三个受体进行了比较，与历史对照组（n=6）谁是相同的治疗，除了气管插管和模拟胃抽吸。在术后第50天活检后不久，对两只实验动物实施了安乐死，其肺无活力。两例患者的自体肺均正常。第三只动物存活了180多天，没有慢性排斥反应的证据。免疫抑制治疗后，通过直接同种异体反应（细胞介导的淋巴细胞溶解，混合淋巴细胞反应）测定，所有动物均表现出供体特异性低反应性。然而，在所有动物中均观察到对合成供体衍生的I类肽的显著反应。在排斥移植物的动物中观察到更明显和扩散的反应。历史对照组显示中期移植物存活，大多数动物存在慢性排斥反应，如前所述。在肺移植后GERD模型中，观察到一系列临床结局。体外数据表明，酸反流增强了间接同种异体反应处理供体I类抗原，给予机制的方式，GERD可能是有害的移植肺的洞察。
Introduction. Lung transplant recipients with documented gastroesophageal reflux disease (GERD) are at increased risk for graft dysfunction. Here, we present the first large-animal model of gastric aspiration after allogeneic lung transplantation and some preliminary data demonstrating the effect of chronic aspiration on the direct and indirect pathways of allorecognition.Methods. Left orthotopic lung transplants (n=3) were performed in miniature swine across a major histocompatibility complex class I disparity, followed by 12 days of high-dose cyclosporine A. At the time of transplantation, a transtracheal catheter was placed at the carina, above the bronchial anastomosis. A gastrostomy tube was placed for daily aspiration of gastric contents. Subsequently, graft lungs were instilled with gastric aspirate daily (3 mL/hr X 8 hr/day) for 50 days. Recipients were followed up with daily complete blood count, scheduled chest radiographs, and biopsies. In vitro studies, including cell-mediated lympholysis, mixed lymphocyte reactions, and peptide proliferation assays, were performed. Results from these three recipients were compared with those of historical controls (n=6) who were treated identically, except for the tracheal cannulation and simulated gastric aspiration.Results. Two of the experimental animals were euthanized with nonviable lungs soon after the postoperative day 50 biopsy. In both cases the native lung was normal. The third animal survived over 180 days without the evidence of chronic rejection. After immunosuppressive treatment, all animals demonstrated donor-specific hyporesponsiveness by assays of direct alloresponse (cell-mediated lympholysis, mixed lymphocyte reaction). A significant response to synthetic donor-derived class I peptide, however, was seen in all animals. A more pronounced and diffuse response was seen in the animals rejecting their grafts. The historical controls showed medium-term graft survival with evidence of chronic rejection in the majority of animals, as previously reported.Conclusion. In a model of GERD after lung transplantation, a spectrum of clinical outcomes was observed. The in vitro data suggest that acid reflux enhances the indirect alloresponse to processed donor class I antigen, giving mechanistic insight into the manner in which GERD may be deleterious to the transplanted lung.