Controlled rewarming as novel end-ischemic therapy for cold stored liver grafts (CORNET)

Project start
Institution: University Hospital Essen
Applicant: Thomas Minor
EKFS funding line: key project
The adverse effects of extended ischemic storage times, for instance, can be alleviated by a short period of subsequent hypothermic oxygenated machine perfusion.

The quality of marginal donor grafts can be significantly improved by changing the modalities of organ preservation or by the use of techniques that allow for revitalizing of the ischemic tissue prior to transplantation. The adverse effects of extended ischemic storage times, for instance, can be alleviated by a short period of subsequent hypothermic oxygenated machine perfusion. 

Experimental work preceding this project has been able to demonstrate that the protective effect of this procedure can be significantly improved by a limited and slow proceeding elevation of the temperature during oxygenated machine perfusion (controlled oxygenated rewarming). 

One mechanistic background to this organ-protective effect has been delineated to be a better restitution of mitochondrial energy metabolism, minimizing e.g. oxygen free radical mediated cell and tissue injury by means of a slow and more gentle activation of cell metabolism as well as the mitigation of a genuine rewarming injury affecting cold stored tissue upon abrupt warming up during reperfusion. A series of individual treatments recently performed on marginal livers in our clinic has been applied without complications and resulted in apparently good graft recovery post-transplantation. 

The aim of the present feasibility project is to test this protocol of controlled oxygenated rewarming by machine perfusion as means to improve graft quality of human donor livers in a first randomized and controlled feasibility study.

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