TY - JOUR
T1 - Early innate immune events induced by prolonged cold ischemia exacerbate allograft vasculopathy
AU - Devitt, Jennifer J.
AU - King, Chelsey L.
AU - Lee, Timothy D.G.
AU - Hancock Friesen, Camille L.
N1 - Funding Information:
The authors would like to thank Brenda Ross for her microsurgical expertise. This work was funded by a Dalhousie University Faculty of Medicine Clinical Scholar Award. The funding body had no role in the design, collection, analysis, or writing of this manuscript.
PY - 2011/1/6
Y1 - 2011/1/6
N2 - Background: Ischemia/reperfusion induced innate immune injury is inescapable in solid organ transplantation. Prolonged cold ischemia exacerbates the primary manifestation of late graft rejection, allograft vasculopathy (AV). The relationship between prolonged cold ischemia and late graft events is unclear and the subject of this study.Methods: Aortic interposition transplants were performed between fully disparate mice treated with CyclosporineA. Allografts were exposed to 20 min or 60 min of cold ischemia and harvested between 1 d-6 wk. Lesion size, smooth muscle cells (SMC), neutrophils (N∅), and CD8+ T cells were quantified.Results: Early SMC loss was identical in both groups. When compared to 20 min cold ischemia, grafts exposed to 60 min exhibited greater early N∅ influx, greater SMC proliferation but fewer medial SMC at 1 wk and 2 wk. Subsequently, earlier and greater CD8+ T cell infiltration were seen in the 60 min group with larger lesions at every time point.Conclusions: These data suggest that the larger neointimal lesions in grafts exposed to 60 min cold ischemia result from enhanced early innate immune events resulting in impaired SMC recovery and subsequent increased adaptive immune response.
AB - Background: Ischemia/reperfusion induced innate immune injury is inescapable in solid organ transplantation. Prolonged cold ischemia exacerbates the primary manifestation of late graft rejection, allograft vasculopathy (AV). The relationship between prolonged cold ischemia and late graft events is unclear and the subject of this study.Methods: Aortic interposition transplants were performed between fully disparate mice treated with CyclosporineA. Allografts were exposed to 20 min or 60 min of cold ischemia and harvested between 1 d-6 wk. Lesion size, smooth muscle cells (SMC), neutrophils (N∅), and CD8+ T cells were quantified.Results: Early SMC loss was identical in both groups. When compared to 20 min cold ischemia, grafts exposed to 60 min exhibited greater early N∅ influx, greater SMC proliferation but fewer medial SMC at 1 wk and 2 wk. Subsequently, earlier and greater CD8+ T cell infiltration were seen in the 60 min group with larger lesions at every time point.Conclusions: These data suggest that the larger neointimal lesions in grafts exposed to 60 min cold ischemia result from enhanced early innate immune events resulting in impaired SMC recovery and subsequent increased adaptive immune response.
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U2 - 10.1186/1749-8090-6-2
DO - 10.1186/1749-8090-6-2
M3 - Article
C2 - 21211039
AN - SCOPUS:78650868875
SN - 1749-8090
VL - 6
JO - Journal of Cardiothoracic Surgery
JF - Journal of Cardiothoracic Surgery
IS - 1
M1 - 2
ER -