Kuromoto N, Hardy M A, Fawwaz R, Reemtsma K, Nowygrod R
J Surg Res. 1984 May;36(5):428-32. doi: 10.1016/0022-4804(84)90122-7.
Short-term peritransplant treatment utilizing 2-dose ALG and 1-dose Palladium-109-hematoporphyrin (PD-H) for selective lymphoid irradiation (SLI) leads to donor-specific permanent acceptance of heart allografts in the Fisher to Lewis rat model. The same treatment significantly prolongs survival of hearts transplanted to strongly histoincompatable , presensitized, and xenogeneic recipients. The purpose of this study was to evaluate synergistic effects of short-term, low-dose cyclosporin treatment and SLI in an attempt to develop a nontoxic protocol utilizing peritransplant treatment for immune preconditioning with minimal subsequent immunosuppression. Single-agent treatment alone with cyclosporin, ALG, or Pd-H resulted in a maximal mean graft survival time (MST) of 33 days. Immunosuppression with 1-dose Pd-H, 2-dose ALG, and low-dose cyclosporin (5 mg/kg) for 14 days doubled the MST to 78 days. Use of therapeutic-dose cyclosporin (20 mg/kg), given for just 3 days, was also quite effective, MST of 57 days with SLI and 43 days with ALG, but toxic; 3 of 12 recipients died of infection with functioning grafts. These results demonstrate that the use of low-dose cyclosporin over a short interval, when combined with peritransplant SLI, is a highly effective and safe method for prolonging heart allograft survival.
在Fisher到Lewis大鼠模型中，利用两剂抗淋巴细胞球蛋白（ALG）和一剂钯-109-血卟啉（PD-H）进行短期移植期治疗以进行选择性淋巴照射（SLI），可导致心脏同种异体移植物被供体特异性永久接受。相同的治疗可显著延长移植到组织高度不相容、预先致敏和异种受体的心脏的存活时间。本研究的目的是评估短期、低剂量环孢素治疗与SLI的协同作用，试图开发一种无毒方案，利用移植期治疗进行免疫预处理，同时尽量减少后续的免疫抑制。单独使用环孢素、ALG或Pd-H单药治疗导致最大平均移植物存活时间（MST）为33天。使用一剂Pd-H、两剂ALG和低剂量环孢素（5毫克/千克）进行14天的免疫抑制可使MST加倍至78天。仅给予3天的治疗剂量环孢素（20毫克/千克）也相当有效，SLI组的MST为57天，ALG组为43天，但有毒性；12只受体中有3只因功能正常的移植物感染而死亡。这些结果表明，短期使用低剂量环孢素并结合移植期SLI，是延长心脏同种异体移植物存活时间的一种高效且安全的方法。
