Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

A critical imbalance exists between the number of people awaiting heart transplantation, and the number of donor hearts available. This imbalance is associated with significant mortality for individuals on transplant wait-lists. Solid organ transplantation has traditionally involved the use of brain-dead organ donors. Over the last decade, the use of organs from donors who have died a circulatory death (DCD) has proven feasible in solid-organ transplantation, and has resulted in acceptable outcomes for lung, liver, kidney, and pancreas transplantation. By ensuring the ethical treatment of DCD organ donors, a consequent trade-off is that the DCD process is associated with a period of obligatory organ injury. As a result of the heart's unique sensitivity to this period of injury, the field of DCD cardiac transplantation requires further investigation, and is not currently feasible in humans. With the aim of improving DCD cardiac function, several groups have investigated the mechanisms by which DCD hearts incur injury, and have demonstrated ways of resuscitating DCD hearts after removal. However, scant effort has been directed at opportunities to protect the DCD heart prior to the period of obligatory injury. Using rodent models of DCD, our group proposes to extensively characterize the cardiac injury associated with DCD, and demonstrate that DCD hearts are potentially viable for transplantation. Subsequently, we propose to study strategies for protecting DCD hearts prior to the period of obligatory injury. Several classes of agents, known to have cardiac protective effects from related areas of research, will be investigated for their potential to improve DCD heart function. The proposed research has significant potential to advance the field of DCD cardiac transplantation. If realized in the clinical setting, DCD cardiac transplantation would help ameliorate the imbalance between heart donors and recipients, and reduce the associated wait-list mortality.