Recovery /preservation of donation cardiac death livers

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DESCRIPTION (provided by applicant): The long term goals of this project is to increase the number of Donation after Cardiac Death (DCD) livers available for transplantation by developing a clinically relevant hypothermic machine perfusion (HMP) method for recovery and preservation. Currently, DCD livers are transplantable and have the potential to increase the donor pool 20-40%. However, they are largely under utilized due to poor preservation by the current method of simple cold storage (SCS). HMP has been shown to improve recovery and preservation of DCD kidneys, but this technology has not been successfully transferred to the liver. Studies show that HMP can improve graft survival in animal models. In addition, oxygenation during HMP improved functional recovery suggesting the importance of restoring tissue energy stores. The goal of this Phase I STTR is to test the feasibility of HMP to recover and preserve DCD livers in the porcine model by accomplishing the following Specific Aims: 1) Scale-up current HMP system for large animal studies and 2) compare post-storage function of porcine livers in an isolated perfusion system following 10 hour preservation for 3 groups, 1) heart-beating + SCS, 2) DCD (30min WI) + SCS, and 3) DCD (30min WI) + HMP. The scale-up system will include oxygenation and dual flow controlled perfusion to the portal vein and hepatic artery to improve flow homogeneity. Functional recovery will be evaluated in an isolated perfusion system which allows greater control and assessment with a broad spectrum of endpoints. Hepatocellular and endothelial functions and damage will be assessed by bile production, indocyanine green secretion, hyaluronic acid uptake, tissue energy state, oxygen consumption, histology, and release of enzymes. This system can assess whether grafts experience primary non-function, a major cause of failure in DCD organs. The success of this project will be directly related to the establishment of a critical partnership between the team of transplant surgeons, the scientists and biomedical engineers who will collaboratively test and modify as needed the procedure for preserving DCD livers. This project will form the basis for further testing in a Phase II STTR application for recovery and preservation of DCD livers in a clinically relevant transplant model. Future plans include joint projects with Organ Recovery Systems (a developer of a liver transplant device) to combine technologies to develop a viable device and protocol to recover and preserve DCD livers.