Ischemia–Reperfusion Injury in Reconstructive Transplantation: An Undefined Conundrum
Published on Jan 1, 2015
· DOI :10.1007/978-1-4939-2071-6_22
Ischemia–reperfusion injury (IRI), a major complication of organ transplantation, tissue resection, and hemorrhagic shock, is a dynamic process that involves two interrelated phases of local ischemic insult and inflammation-mediated reperfusion injury. This chapter highlights recent mechanistic insights into innate–adaptive immune cross talk and cell activation cascades leading to inflammation-mediated damage in IR-stressed tissues, and considers their pathophysiological relevance in the emerging field of vascularized composite allotransplantation (VCA). The interlocked molecular signaling pathways in histologically divergent cell types, the IRI kinetics, and positive versus negative regulatory loops at the innate–adaptive immune interface are discussed. Current gaps in our knowledge and mechanistic aspects necessitating basic and translational research are stressed. Improved appreciation of cellular and molecular events, which trigger and sustain local inflammation responses in experimental models, are fundamental to developing innovative strategies for treating VCAs suffering from IR-inflammation/dysfunction following prolonged periods of ex vivo storage. Achieving these goals should pave the road to improving the clinical outcomes and possibly achieving the ultimate goal of imposing operational immune tolerance in transplant patients.