Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Heart failure is a major problem in Canada and across the world, and heart transplantation is the only option that cures the patient. However, we don't have enough hearts to go around for everyone, in part due to the limitations of transporting them on ice. Ex-vivo heart perfusion (EVHP) is a technology that allows us to reanimate the heart outside the body during transport using a machine, by providing oxygen and nutritional support. This helps us transport the heart further, and with less damage to the organ. However, EVHP still has limited capacity to lengthen preservation times, and may not be optimal for some types of donors. By changing certain additives in the heart preservation solution used during EVHP, we hypothesize that we can optimize preservation of the heart for certain donor types. To investigate, we will use a pig model to mimic the conditions experienced by different types of donors before procurement and placement of the heart on an EVHP apparatus, comparing what happens within the tissue between them to derive insights for therapeutic strategies. To improve EVHP, we will trial a reduction in sugar provision alongside the addition of known heart-protective substrates: these are hypothesized to better accommodate for the biochemical stressors experienced by the heart on the EVHP machine. We can directly monitor functional output of the heart on the machine, and we will investigate tissue-level insights to understand what is occurring molecularly. Finally, after optimizing dosages of the additives and characterizing tissue-level impacts, we will undertake pig heart transplants to verify that benefits translate to post-transplantation. This has the potential to greatly impact heart transplant access by better facilitating donor organs and allowing access to donor organs that are currently regarded as sub-optimal. The research will also provide insights into the molecular mechanisms of heart failure, helping improve treatment before transplantation.