Cold ischemic injury accelerates the progression to chronic rejection in a rat cardiac allograft model

Richard J. Knight, Steven Dikman, Hui Liu, Giorgio P. Martinelli

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71 Scopus citations


Background. The pathogenesis of chronic rejection likely involves an interplay between immunogenic and nonimmunogenic factors. The objective of this study was to determine the influence of cold ischemic preservation injury on the rate of progression to chronic rejection in the Lewis to F344 cardiac allograft model. Methods. To induce an ischemic injury, donor hearts were stored for 3 hr at 4°C in University of Wisconsin solution before transplantation. Allografts were excised at 1, 7, and 90 days after transplantation or at rejection. Vasculopathy was graded for degree of intimal thickening based on the involvement of vascular perimeter and luminal compromise. Results. The degree of vessel injury in ischemic injured allografts at 90 days was significantly greater than in nonischemic injured allografts (2.8±0.4 vs. 1.6±0.5, P<0.05). Ischemic injury in syngeneic grafts did not induce a vasculopathy. Immunoperoxidase staining with R73 (anti-T cell) and ED1 (anti-macrophage) monoclonal antibodies revealed that, in ischemic injured allografts at 90 days after transplantation, the infiltrate was composed predominantly of T cells and macrophages. Additionally, ischemic injured allografts excised at 7 days after transplantation showed cellular infiltrates composed of R73-positive T cells and rare interleukin-2 receptor-positive cells, which was not observed in nonischemic allografts or ischemic syngeneic grafts. Conclusions. The progression to chronic vasculopathy in this model is principally an immunologic pro- cess, which is accelerated by an ischemic insult to the allograft. The vascular injury is mediated in part by T cells and macrophages.

Original languageEnglish (US)
Pages (from-to)1102-1107
Number of pages6
Issue number8
StatePublished - Oct 27 1997

ASJC Scopus subject areas

  • Transplantation


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