Toledo-Pereyra L H, Mackenzie G H, Gordon D A, Gof S, Bandlien K
J Urol. 1984 Apr;131(4):777-80. doi: 10.1016/s0022-5347(17)50623-0.
This study applies cyclosporin A as a donor pretreatment prior to organ harvesting or as a graft pretreatment during preservation of canine kidney allografts by hypothermic pulsatile perfusion or hypothermic storage. All recipients except those in Group IX received minimal immunosuppression with azathioprine after transplantation (5 to 2.5 mg. per kg. per day). No significant differences in survival (X +/- SD) were observed between the 3 control groups which were either 1) flushed with untreated Ringer's lactate solution and immediately transplanted (Group I, no. = 8, 14 +/- 3.33 days), 2) preserved by hypothermic pulsatile perfusion for 24 hours (Group II, no. = 7, 12.0 +/- 8.92 days), or 3) hypothermically stored for 24 hours (Group III, no. = 7 13.1 +/- 11.6 days). A trend towards improved survival was seen in the 2 groups of animals that received kidneys that had been graft pretreated with cyclosporin A (12.5 mg.) during 24 hours preservation by either hypothermic pulsatile perfusion (Group IV, no. = 10, 17.4 +/- 13.32 days, p less than .25) or hypothermic storage (Group V, no. = 6, 8 +/- 12.75 days, p less than .25). Survival of recipients in Groups VI (no. = 6) and VII (no. = 9) who received kidneys whose donors had been pretreated with 25 and 50 mg. per kg. respectively was dependent on the dosage of cyclosporin A used. Donor pretreatment at 50 mg. per kg. was deleterious to kidney function (Group VI, 2.16 +/- 1.47 days, p less than 0.0005). Donor pretreatment with 25 mg. per kg. did not significantly improve survival over control groups (15.66 +/- 12.9 days). Recipients in Groups VIII (no. = 10) and IX (no. = 6) were transplanted with kidneys from cyclosporin A pretreated donors (15 mg. per kg.). These kidneys also received cyclosporin A graft pretreatment (10 mg.) during 24 hours of hypothermic storage. The only difference between Groups VIII and IX was that the animals in Group IX received minimal amounts of cyclosporin A (5 mg. per kg. per day) after transplantation. Combined donor and graft pretreatment yielded improved kidney allograft survival (Group VIII, 21.7 +/- 13.36 days, p greater than .10, Group IX, 20.83 +/- 14.2 days, p greater than .10). However, there was no significant difference observed as a result of the different immunosuppressive protocols used in Groups VIII and IX. These results indicate a trend towards improved renal allograft survival under certain conditions, after donor and graft pretreatment with cyclosporin A.
本研究将环孢素A用作供体预处理，即在器官摘取前进行处理，或用作移植物预处理，即在通过低温搏动灌注或低温保存法保存犬肾同种异体移植物期间进行处理。除第IX组外，所有受体在移植后均接受硫唑嘌呤的最小剂量免疫抑制（每天每千克体重5至2.5毫克）。在3个对照组之间未观察到存活时间（X±标准差）的显著差异，这3个对照组分别为：1）用未处理的乳酸林格液冲洗并立即移植（第I组，n = 8，14±3.33天）；2）通过低温搏动灌注保存24小时（第II组，n = 7，12.0±8.92天）；3）低温保存24小时（第III组，n = 7，13.1±11.6天）。在两组接受经环孢素A（12.5毫克）移植物预处理的肾脏的动物中，观察到存活时间有改善的趋势，这两组动物的肾脏分别通过低温搏动灌注（第IV组，n = 10，17.4±13.32天，p＜0.25）或低温保存（第V组，n = 6，8±12.75天，p＜0.25）法保存24小时。第VI组（n = 6）和第VII组（n = 9）的受体接受的肾脏，其供体分别用每千克体重25毫克和50毫克的环孢素A进行了预处理，其存活情况取决于所用环孢素A的剂量。每千克体重50毫克的供体预处理对肾功能有害（第VI组，2.16±1.47天，p＜0.0005）。每千克体重25毫克的供体预处理与对照组相比，并未显著提高存活率（15.66±12.9天）。第VIII组（n = 10）和第IX组（n = 6）的受体移植了来自经环孢素A预处理（每千克体重15毫克）的供体的肾脏。这些肾脏在低温保存24小时期间也接受了环孢素A移植物预处理（10毫克）。第VIII组和第IX组之间的唯一区别在于，第IX组的动物在移植后接受了最小剂量的环孢素A（每天每千克体重5毫克）。供体和移植物联合预处理提高了肾同种异体移植物的存活率（第VIII组，21.7±13.36天，p＞0.10，第IX组，20.83±14.2天，p＞0.10）。然而，第VIII组和第IX组使用的不同免疫抑制方案并未导致显著差异。这些结果表明，在某些条件下，经环孢素A对供体和移植物进行预处理后，肾同种异体移植物的存活率有改善的趋势。
