Evaluation of Hypothermic Oxygenated Perfusion Ex-Vivo Heart Perfusion to Expand the Donor Pool and Improve Transplant Outcomes

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Heart transplantation is the best treatment option for selected patients with severe heart failure. As the number of donor hearts is limited, every year, fewer than 200 patients in the UK receive this treatment, but we know approximately 2000 patients younger than 65 years die of heart failure. On the other hand, many hearts kindly donated by the brain death donors (DBD) are not being transplanted due to the concerns about how well they may work following storage outside the body and the difficult transplant operation. Hearts from older donors and those with thickened heart muscles are not used because they deteriorate too much during storage. The traditional method to store heart outside human body, an ice box, deprives heart of oxygen. When blood flow to the heart is resumed in a recipient's body, the sudden supply of oxygen to the energy- and nutrient-depleted heart causes damage, called ischaemia reperfusion (IR) injury. This markedly reduces the function of the heart and is the commonest cause of death after transplant, so we only select the best hearts and allow them to be stored in the ice box for a maximum of 4 hours. Donation from non-heart beating, or donation after circulatory death (DCD), a field in which the UK leads the world, has the potential to increase number of heart transplants by 30%. However, as these DCD hearts have to be supplied with oxygen soon after being removed from donor bodies, they rely on a machine pumping blood around the arteries for storage and transportation. The only available machine maintains donor hearts in beating state at a warm temperature (34 degree Celsius). However, its cost, £32k per usage, is too expensive for it to be widely adopted. A new method Hypothermic Oxygenated Perfusion (HOP), which pumps blood with oxygen at low temperature (8 degree Celsius) to store heart outside human body has been developed. We believe it is better than the ice box, because donor hearts inside it receive nutrient and oxygen during storage. In the laboratory this gives good results, but has yet to be proven for the human heart, and particularly for some of the hearts we currently turn down for use. We want to show that there is less damage to the heart muscle cells, and this results in a stronger beating heart. We also want to show that the storage time can be extended for up to 12 hours. We plan to store 10 DBD and 10 DCD human hearts, that are declined for clinical transplantation but donated for research, using HOP for 4-12 hours; and another group of 10 DBD hearts using the ice box for 4 hours. After this period of storage, they will be put onto a testing circuit and provided with blood-based nutrient-rich solution, which mimics the transplant into a recipient, but in the laboratory, for another 4 hours. We will take samples of the heart muscles and solution in the circuit, and record the strength of the heart contractions. First, we would like to test whether the DBD and DCD hearts, that are not accepted for clinical transplant, have good function after being stored by HOP for up to 12 hours. Second, experiments on the samples will be performed to compare how many heart muscles cells are dead or damaged and whether this correlates with the strength of the heart contractions. In addition, we will look for markers which can be easily and quickly measured and reflect the donor heart quality. Similar samples will be taken during clinical heart transplantation. We will test whether the markers that we found also predict heart function after transplantation in patients. With a better understanding of how HOP works to protect heart quality, we hope to use this method to increase the number of hearts being transplanted, lengthen the storage period, and improve the heart transplant outcomes. Overall, we would like to study whether this new heart storage method will make more patients on the waiting list benefit from heart transplantation.