49. Cytoprotection strategies – I/R injury and opportunities for organ repair

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Ischemia/reperfusion injury (I/R) is a complex set of pathological changes which results from removal of cells and tissues from the body and manipulation in vitro; (I/R applies especially to vascularised large tissue blocks or organs, which can be considered together as complex tissue allografts – CTA). The injuries are expressed at the point of re-implantation into the recipient patient and can progressively accumulate over a subsequent time period (in some cases beyond 24 h). The steps in organ cryobanking (organ retrieval, initial blood washout, perfusion to add or remove cryoprotective agents, and cooling and warming to ultralow temperatures) are all potential inducers of I/R responses. I/R has been linked to number of different effects, including oxidative stress, signalling of cellular damage pathways, and recruitment of inflammatory responses. These will be outlined briefly to orientate the discussion. Evidence of these pathways have been reported in some cryopreservation studies on cells and tissues, but there is a scarcity of information about I/R in CTA cryobanking. For vascularised CTA, there are additional consequences of I/R which may impact the host immune system and injure distant organ systems. A number of pharmacological agents and therapeutic strategies have been shown to ameliorate different aspects of I/R, and these will be outlined; however, a holistic treatment can be complex and challenging. Approaches to understanding I/R and developing effective cytoprotective strategies will become an important and essential new research area within novel cryobanking strategies for CTA.