Beneficial effects of perioperative low-dose inhaled carbon monoxide on pulmonary allograft survival in MHC-inbred CLAWN miniature swine.
Beneficial effects of perioperative low-dose inhaled carbon monoxide on pulmonary allograft survival in MHC-inbred CLAWN miniature swine.
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围手术期低剂量吸入一氧化碳对 MHC 近交 CLAWN 小型猪肺同种异体移植物存活的有益影响。
DOI：
10.1097/tp.0b013e3181ff8730
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发表时间：
2010
期刊：
影响因子：
6.2
通讯作者：
Yamada,Kazuhiko
中科院分区：
文献类型：
--
作者：
Sahara,Hisashi;Shimizu,Akira;Setoyama,Kentaro;Oku,Manei;Okumi,Masayoshi;Nishimura,Hiroaki;Oriyanhan,Wunimenghe;Tasaki,Masayuki;Scalea,Joseph;Wada,Hiromi;Bando,Toru;Date,Hiroshi;Yamada,Kazuhiko
Background.We have recently reported that perioperative low-dose carbon monoxide (CO) inhalation decreases lung ischemia-reperfusion injury in miniature swine. The aims of this study were to establish a large animal model of pulmonary allograft rejection using polymerase chain reaction-typed major histocompatibility complex (MHC)-inbred CLAWN miniature swine and to examine the effects of CO on allograft survival.Methods.Eleven CLAWN miniature swines received fully MHC-mismatched lungs followed by 12 days of tacrolimus (days 0–11; blood level 35–45 ng/mL). Six recipients received tacrolimus alone (control group). Five recipients were additionally treated with inhaled CO (180 min for donors until graft harvest; 390 min for recipients until 2 hr after reperfusion).Results.All recipients treated with tacrolimus alone uniformly rejected their grafts by postoperative day 63 with development of cytotoxic antidonor antibodies. CO treatment was effective in prolonging allograft survival from a mean of 47±7 to 82±13 days (P= 0.017), with one CO-treated animal maintaining function until postoperative day 120. Development of antidonor antibodies and donor-specific responsiveness by cell-mediated lympholysis and mixed lymphocyte reaction assays was delayed in animals that received CO therapy. Furthermore, serum concentrations of proinflammatory cytokines (interleukin-1β and-6) 1 day after transplant were significantly decreased in the CO-treated group.Conclusions.Fully MHC-mismatched lungs in CLAWN miniature swine were consistently rejected within 63 days, suggesting that this is a robust large animal model ideal for investigating mechanisms and treatment of lung rejection. Perioperative low-dose CO inhalation prolonged graft survival and inhibited antidonor antibody production and was associated with decreased proinflammatory mediators in this model.
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