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The Journal of Cardiovascular Surgery 2000 June;41(3):487-92

Copyright © 2009 EDIZIONI MINERVA MEDICA

language: English

Short-course immunosuppression using FK506 for rat tracheal allografts

Hashimoto M., Nakanishi R., Muranaka H., Umesue M., Eifuku R., Yasumoto K.

From the Second Department of Surgery School of Medicine University of Occupational and Environmental Health Kitakyushu, Japan


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Background. A min­i­miz­ing immu­no­sup­pres­sion ­after a tra­cheal allo­tran­splan­ta­tion is desir­able.
Methods. We exam­ined the use­ful­ness of a ­short-­course of immu­no­sup­pres­sion ­after tra­cheal allo­tran­splan­ta­tion in rat. Each trans­plant con­sist­ing of a 5-­ring seg­ment was het­er­o­top­i­cal­ly implant­ed ­into the omen­tum. Four ani­mals under­went a syn­ge­ne­ic trans­plan­ta­tion and ­thus ­served as con­trols (­Group A). Thirty ani­mals under­went an allog­e­ne­ic trans­plan­ta­tion and ­were ran­dom­ly clas­si­fied ­into 4 ­groups as fol­lows: No immu­no­sup­pres­sion (­Group B, n=6), treat­ment ­with 0.5 mg/kg of Tacrolims (FK506) (­Group C, n=8), 1.0 mg/kg of FK506 (­Group D, n=8), and 1.5 mg/kg of FK506 (­Group E, n=8). Different dos­es of FK506 ­were admin­is­tered intra­mus­cu­lar­ly for ­only ­three con­sec­u­tive ­days ­after het­er­o­top­ic tra­cheal allo­tran­splan­ta­tion. The ser­um lev­els of FK506 ­were ­then inves­ti­gat­ed 3, 7, 14, 21, and 28 ­days ­after trans­plan­ta­tion in ­groups C, D, and E. All ­rats ­were ­killed 28 ­days ­after trans­plan­ta­tion and ­then the implant­ed tra­cheae ­were har­vest­ed, and eval­u­at­ed his­to­log­i­cal­ly.
Results. All ani­mals sur­vived for the pro­to­col peri­od. The ­graft mor­phol­o­gy of ­Group E was sig­nif­i­cant­ly bet­ter ­than ­that of ­groups B, C, and D regard­ing ­both mac­ro- and micros­co­py, and ­also ­showed the ­same find­ings as ­that of ­Group A, ­except for low-­grade mono­nu­cle­ar ­cell infil­tra­tion. Only in ­Group E, the FK506 ­blood lev­el was main­tained at ­over 0.5 ng/ml, ­which is the low­est detect­able lim­it in ­this ­assay, ­until 21 ­days ­after trans­plan­ta­tion.
Conclusions. We ­thus con­clude ­that 1.5 mg/kg of FK506 ­which was admin­is­tered for ­only ­three con­sec­u­tive ­days ­after sur­gery may be ­used to main­tain the mor­phol­o­gy of tra­cheal allo­grafts in ­rats for 28 ­days ­after trans­plan­ta­tion.

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