Grant: CIHR Fellowship

Heart transplant is a life saving treatment for patients with end-stage heart failure; however, because of a critical shortage of donor organs many patients die while waiting for a heart transplant. There are two categories of organ donors: brain dead donors and donors after circulatory death (DCD). Currently only hearts from brain dead donors are used for transplant. DCD hearts are without blood flow and oxygen for a period of time (ischemia) before they can be harvested. Restoring blood flow (reperfusion) triggers calcium buildup inside heart cells and causes heart muscle to die (ischemia-reperfusion injury). DCD hearts are not used because of concern that ischemia-reperfusion injury causes the heart to be too weak for transplant; however, a drug called SEA-0400 has been shown to reduce the accumulation of calcium inside heart cells and minimize ischemia-reperfusion injury in mice and rat hearts. The objective of this project is to determine if SEA-0400 can reduce the accumulation of calcium inside pig heart cells, minimize ischemia-reperfusion injury, and facilitate transplantation of DCD pig hearts. We will achieve this objective with two experiments. Experiment 1) We will isolate individual cells from pig hearts and determine what dose of SEA-0400 minimizes calcium build-up during ischemia and reperfusion. These results will be used to inform the following transplant experiments. Experiment 2) We have developed a pig model of DCD that closely resembles what happens in human patients. We will administer SEA-0400 to DCD pig hearts and transplant them into a recipient pig. We will determine if SEA-0400 can minimize ischemia-reperfusion injury and improve heart function after transplant. Very few research projects have studied if DCD hearts can be used for transplant. SEA-0400 could minimize ischemia-reperfusion injury in DCD hearts, increase the number of donor hearts, and save the lives of patients waiting for a heart transplant.