3 years ago

The Effects of Brain Death and Ischemia on Tolerance Induction are Organ-Specific

D H Sachs, J C Madsen, J S Allan, M Sekijima, G M I I LaMuraglia, M L L Madariaga, V Villani, R B Colvin, S G Michel, B R Rosengard, E A Farkash, K Yamada
We have previously shown that 12 days of high-dose calcineurin inhibition induced tolerance in MHC inbred miniature swine receiving MHC-mismatched lung, kidney, or co-transplanted heart/kidney allografts. However, if lung grafts were procured from brain dead donors, and transplanted alone, they were rejected within 19-45 days. Here, we investigated whether donor brain death with or without allograft ischemia would also prevent tolerance induction in kidney or heart/kidney recipients. Four kidney recipients treated with 12 days of calcineurin inhibition received organs from donors rendered brain dead for 4 hours. Six heart/kidney recipients also treated with calcineurin inhibition received organs from donors rendered brain dead for 4 hours, 8 hours or 4 hours with 4 additional hours of cold storage. In contrast to lung allograft recipients, all isolated kidney or heart/kidney recipients that received organs from brain dead donors achieved long term survival (> 100 days) without histologic evidence of rejection. Pro-inflammatory cytokine gene expression was upregulated in lungs and hearts, but not kidney allografts after brain death. These data suggest that the deleterious effects of brain death and ischemia on tolerance induction are organ-specific, which has implications in the application of tolerance to clinical transplantation. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/ajt.14674

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