Genetic and Nutritional Preconditioning against Ischemia/Reperfusion Injury

Organ transplantation is considered to be one of the greatest achievements in modern medicine during the last decades. Improvements in tissue typing for the human leukocyte antigens (HLA) class II antigens, organ preservation, surgery, and the use of immunosuppressive drugs made organ transplantation the treatment of choice for patients with end-stage organ failure. The success of organ transplantation has led to a marked increase in the number of transplantations. However, with only a limited number of transplantable organs available from living donors, the demand for donor organs has far exceeded the supply. To expand the organ donor pool, the transplant community searched for alternatives e.g. through the use of donors after cardiac death. Organs donated after cardiac death are considered less than optimal. The extended time from the termination of the circulation, to the actual moment of death, to organ recovery, and, finally, to the initiation of perfusion with cold preservation solutions results in the initiation of irreversible ischemia/reperfusion (I/R) injury. On transplantation in the recipient, reperfusion of the graft triggers apoptotic cell death, and promotes the activation of an inflammatory response, resulting in profound injury of the graft. Hence, I/R injury is considered a risk factor for the development of delayed graft function, primary non-function, and acute rejection of the graft. The treatment of I/R injury is still unsatisfactory. Therefore, new therapeutic interventions to reduce or prevent I/R injury remain warranted. The studies in this thesis describe two novel treatments to ameliorate I/R injury: genetic and nutritional preconditioning.

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