Gruessner R W, Nakhleh R E, Harmon J V, Dunning M, Gruessner A C
Department of Surgery, University of Minnesota, Minneapolis 55455, USA.
Transplantation. 1998 Jul 27;66(2):164-9. doi: 10.1097/00007890-199807270-00004.
Unlike in kidney and heart transplantation, the role of pretransplant donor-specific blood transfusion (DST) has not been studied prospectively in a large animal model of bowel transplantation. We investigated the impact of portal versus systemic DST on overall survival, rejection, graft-versus-host disease (GVHD), and infection after total (small and large) bowel transplantation in pigs.
Mixed lymphocyte culture-reactive, outbred pigs underwent total enterectomy and orthotopic total bowel transplantation with portal vein graft drainage. One unit of donor blood was transfused via the portal or systemic circulation (according to a randomization protocol) before graft implantation was begun. We studied six groups, all of which underwent at least a total bowel transplant: group 1 (n=5) comprised nonimmunosuppressed control pigs with portal DST; group 2 (n=6), nonimmunosuppressed control pigs with systemic DST; group 3 (n=5), cyclosporine (CsA)-treated pigs with portal DST; group 4 (n=5), CsA-treated pigs with systemic DST; group 5 (n=5), tacrolimus-treated pigs with portal DST; and group 6 (n=5), tacrolimus-treated pigs with systemic DST. All immunosuppressed pigs received prednisone (2 mg/kg/day) and either CsA (to maintain levels between 250 and 350 ng/ml) or tacrolimus (to maintain levels between 10 and 30 ng/ml). Stomal biopsies and autopsies were obtained to study the incidence of rejection, GVHD, and infection.
Portal DST and tacrolimus-based immunosuppression resulted in the highest survival rates. At 7, 14, and 28 days after transplantation, survival rates in group 5 were 100%, 100%, and 80%; in group 6, 100%, 60%, and 40%; and in group 3, 100%, 0%, and 0%, respectively. Only the combination of portal DST and tacrolimus prevented the occurrence of, and death from, rejection. Death from rejection at 7, 14, and 28 days in group 5 was 0%, 0%, and 0%; in group 6, 0%, 33%, and 67%; and in group 3, 0%, 100%, and 100%, respectively. Of note, if immunosuppression was used, the groups with portal (versus systemic) DST had a higher risk of death from infection but a lower risk of death from GVHD. Simultaneous immunologic events were noted more frequently in groups with systemic (versus portal) DST. Long-term survival was noted only in groups with tacrolimus-based immunosuppression and was more common for those with portal (versus systemic) DST.
Portal DST at the time of total bowel transplantation and posttransplant immunosuppression with tacrolimus prevent rejection and significantly increase graft survival. The combination of portal antigen presentation and tacrolimus needs to be studied in clinical bowel transplantation.
与肾脏和心脏移植不同，移植前供体特异性输血（DST）在大型肠道移植动物模型中的作用尚未进行前瞻性研究。我们研究了门静脉与全身DST对猪全（小肠和大肠）肠移植后总体生存、排斥反应、移植物抗宿主病（GVHD）和感染的影响。
混合淋巴细胞培养反应性、远交系猪接受全肠切除术和门静脉移植引流的原位全肠移植。在开始植入移植物前，通过门静脉或全身循环（根据随机方案）输注一单位供体血液。我们研究了六组，所有组均至少接受了全肠移植：第1组（n = 5）为接受门静脉DST的未免疫抑制对照猪；第2组（n = 6）为接受全身DST的未免疫抑制对照猪；第3组（n = 5）为接受环孢素（CsA）治疗且接受门静脉DST的猪；第4组（n = 5）为接受CsA治疗且接受全身DST的猪；第5组（n = 5）为接受他克莫司治疗且接受门静脉DST的猪；第6组（n = 5）为接受他克莫司治疗且接受全身DST的猪。所有免疫抑制猪均接受泼尼松（2 mg/kg/天）以及CsA（维持水平在250至350 ng/ml之间）或他克莫司（维持水平在10至30 ng/ml之间）。获取造口活检和尸检样本以研究排斥反应、GVHD和感染的发生率。
门静脉DST和基于他克莫司的免疫抑制导致最高的生存率。移植后7天、14天和28天，第5组的生存率分别为100%、100%和80%；第6组分别为100%、60%和40%；第3组分别为100%、0%和0%。只有门静脉DST与他克莫司的联合使用可预防排斥反应的发生及其导致的死亡。第5组在移植后7天、14天和28天因排斥反应死亡的比例分别为0%、0%和0%；第6组分别为0%、33%和67%；第3组分别为0%、100%和100%。值得注意的是，若使用免疫抑制，接受门静脉（相对于全身）DST的组因感染死亡的风险较高，但因GVHD死亡的风险较低。在接受全身（相对于门静脉）DST的组中，同时发生的免疫事件更为常见。仅在基于他克莫司免疫抑制的组中观察到长期生存，且在接受门静脉（相对于全身）DST的组中更为常见。
全肠移植时的门静脉DST以及移植后使用他克莫司进行免疫抑制可预防排斥反应并显著提高移植物存活率。门静脉抗原呈递与他克莫司的联合应用需要在临床肠道移植中进行研究。
