ドナーに対する一酸化炭素吸入療法による移植肺生着延長効果

前臨床ミニブタモデルを用いた新たな臓器保存方法への発展

抄録

Carbon monoxide(CO)is produced endogenously as a byproduct of heme catalysis, and has been shown to provide protection against ischemia-reperfusion injury(IRI)in a variety of organs in murine models. Since CO is also known to be a toxic gas, translational research using large animals is essential prior to its use in the clinic. We have extensively studied the beneficial effects of CO inhalation using CLAWN miniature swine and reported that perioperative low-dose CO inhalation decreases lung IRI and that perioperative CO inhalation to both donor and recipient prolongs lung graft survival in MHC-inbred CLAWN miniature swine. To understand the mechanisms involved in prevention of graft damage following CO inhalation, we examined whether donor or recipient treatment alone is sufficient to prolong graft survival. 13 CLAWN swine received fully MHC mismatched lungs with 12 days of tacrolimus(days 0-11；35-45 ng/mL). In the control group(n＝6), recipients received tacrolimus alone. In D group(n＝4), only donor was treated with 200-250 ppm CO for 180 min. In R group(n＝3), 200-250 ppm CO was administered only to the recipient for 390 min until 2-hr reperfusion. All control recipients rejected the grafts by POD63. CO therapy only with donor(D group)was effective in prolonging graft survival. 3 out of 4 recipients accepted the grafts over 63 days. In contrast, all 3 recipients in R group rejected the grafts by POD63. These data suggest that donor CO alone is sufficient to improve lung graft survival in a clinically relevant large animal model.