Cold ischemic injury, aortic allograft vasculopathy, and pro-inflammatory cytokine expression

Background. The aim of this study was to understand the role of ischemic preservation injury and pro-inflammatory cytokine expression in the progression of allograft vasculopathy. Methods. Using the rat aortic transplant model, grafts were stored at 4°C for either 1 or 24 h. Graft vasculopathy was assessed at 4 and 8 weeks after transplantation. Intra-graft cytokine expression was measured at days 1, 3 and, 7 after transplantation. Results. At 4 weeks, intimal hyperplasia of allografts was greater than isografts (P < 0.05). At 8 weeks, all groups had an increase in graft vascular disease compared to the 4-week groups (P < 0.05). Allografts preserved for 24 h displayed a greater degree of vessel-wall reaction than both isograft groups and allografts stored for 1 h (P < 0.05). An increased expression of the cytokines, TNF-α, TGF-β, IL-2, INF-γ, IL-1, and IL-6 was noted in the allografts stored for 24 h compared to similarly treated isografts (P < 0.05). Conclusions. Prolonged ischemic preservation injury induced vascular disease in both isografts and allografts. The vessel wall reaction increased over time and was greater in allografts than isografts. The enhanced expression of T cell- and macrophage associated cytokines in allografts compared to isografts, suggested that early pro-inflammatory cytokine expression played an important role in progression of allograft vasculopathy.