Pharmacological preconditioning and sodium/hydrogen exchange inhibition to optimise preservation of the donor pig heart

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Heart transplantation has become established as an extremely beneficial treatment for patients with end-stage heart failure, however its success is limited by the restricted availability of donor hearts. Many hearts that could be considered for heart transplantation cannot be used because of damage that can occur to potential donor hearts after the death of the donor. This damage is caused in part by deterioration in heart function after death and in part by the process of removal and cold storage that occur prior to transplantation of the heart. This study will examine two new methods of optimising the quality and preservation of the donor heart for transplantation. The treatments to be investigated in this study are aimed at preventing damage to the donor heart after death and during the process of transplantation. The studies will be conducted in a pig model of heart transplantation that we have developed in our laboratory. The treatments will be administered to the donor pig after induction of brain death and also to the recipient during transplantation of the heart. As the model closely mimics all aspects of human heart transplantation, any positive findings that stem from these studies will be directly applicable to human transplantation. Improved preservation of the donor heart will make the operation safer and will potentially increase the number of hearts that can be used for transplantation. As many donors provide multiple organs for transplantation eg kidneys, liver, lungs and pancreas, the treatments that we are investigating have the potential to improve the recovery of all these organs after transplantation.