Pharmacological Preconditioning And Sodium/hydrogen Exchange Inhibition To Optimise Preservation Of The Donor Pig Heart
Funder
National Health and Medical Research Council
Funding Amount
$242,545.00
Summary
Heart transplantation has become established as an extremely beneficial treatment for patients with end-stage heart failure, however its success is limited by the restricted availability of donor hearts. Many hearts that could be considered for heart transplantation cannot be used because of damage that can occur to potential donor hearts after the death of the donor. This damage is caused in part by deterioration in heart function after death and in part by the process of removal and cold stora ....Heart transplantation has become established as an extremely beneficial treatment for patients with end-stage heart failure, however its success is limited by the restricted availability of donor hearts. Many hearts that could be considered for heart transplantation cannot be used because of damage that can occur to potential donor hearts after the death of the donor. This damage is caused in part by deterioration in heart function after death and in part by the process of removal and cold storage that occur prior to transplantation of the heart. This study will examine two new methods of optimising the quality and preservation of the donor heart for transplantation. The treatments to be investigated in this study are aimed at preventing damage to the donor heart after death and during the process of transplantation. The studies will be conducted in a pig model of heart transplantation that we have developed in our laboratory. The treatments will be administered to the donor pig after induction of brain death and also to the recipient during transplantation of the heart. As the model closely mimics all aspects of human heart transplantation, any positive findings that stem from these studies will be directly applicable to human transplantation. Improved preservation of the donor heart will make the operation safer and will potentially increase the number of hearts that can be used for transplantation. As many donors provide multiple organs for transplantation eg kidneys, liver, lungs and pancreas, the treatments that we are investigating have the potential to improve the recovery of all these organs after transplantation.Read moreRead less
Towards A New Normokalemic Arrest Paradigm For Orthotopic Heart Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$489,634.00
Summary
Innovations from Nature to Heart Transplantation:a Real Heart Stopper Heart preservation is limited to 4-6 hours of cold-ischaemic storage (0 to 4 C). The risk of post-transplant death doubles if the donor heart is stored from 1 to 5 hours, and triples with 7 hrs storage times. We have developed a new preservation solution borrowing from natural hibernators that will permit organs to be safely stored for up to 15 hours, and offering new opportunities to organ donors and recipients worldwide.
Complement Regulation: Protection Against Xenograft Rejection, Ischaemia And Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$256,980.00
Summary
Organ transplantation is an accepted solution to treat kidney, heart, lung and liver failure, and is being keenly sought for diabetes treatment. With refined surgical techniques and better controlled immunosuppression, the expected graft survival times are in years. However, the number of individuals who would benefit from transplants exceeds the supply of donor organs, and this number will increase as the benefits of having a transplanted organ increase. There is an active program to research t ....Organ transplantation is an accepted solution to treat kidney, heart, lung and liver failure, and is being keenly sought for diabetes treatment. With refined surgical techniques and better controlled immunosuppression, the expected graft survival times are in years. However, the number of individuals who would benefit from transplants exceeds the supply of donor organs, and this number will increase as the benefits of having a transplanted organ increase. There is an active program to research the possibility of using animal organs (xenografts). This project addresses one of the many issues arising from xenograft transplantation - the rapid activation of the body's complement system, which without treatment results in the very rapid rejection of the graft. In principle this problem can be solved by the development of transgenic donor animals that carry one or more human genes that produce a complement regulating protein, such as CD46 (MCP) or CD55 (DAF). In practice, however, to get successful longterm organ function still requires the selection of the optimal complement regulator or combination of regulators and an understanding of how they function. This research work analyses how CD46 and CD55 function to protect tissues from complement activation, and will result in selection of appropriate transgenes for xenografting. Another aspect of transplantation that is addressed in this proposal is the damage that a graft suffers when the blood supply is temporarily removed during organ harvest and the grafting procedure. This is similar to what occurs during a heart attack when a portion of heart muscle is starved of blood: as the blood flows again through the tissue there is a powerful reaction, again involving complement activation, which is known as reperfusion injury. We have found that perfusing a graft with a soluble form of the CD46 complement regulator provides protection against this damage. The research will measure and optimise this protection.Read moreRead less
Hormonal Resuscitation And P38 MAP Kinase Inhibition To Enhance Quality Of Cadaveric Donor Organs For Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
The transplantation of organs such as the heart, lung, liver, kidney and pancreas from brain-dead donors is limited primarily by the shortage of donor organs. It is now recognised that as many as 25% (one in four) potentially usuable donor organs are lost after brain death due to the rapid deterioration that occurs in organs after brain death. There is evidence that this deterioration is due to loss of the normal hormones that are essential to the normal functioning of these organs. In this proj ....The transplantation of organs such as the heart, lung, liver, kidney and pancreas from brain-dead donors is limited primarily by the shortage of donor organs. It is now recognised that as many as 25% (one in four) potentially usuable donor organs are lost after brain death due to the rapid deterioration that occurs in organs after brain death. There is evidence that this deterioration is due to loss of the normal hormones that are essential to the normal functioning of these organs. In this project, we will use a pig model of brain death that we have extablished in our laboratory to examine the effects of hormone replacement on the function of organs that are used for transplantation. We will also test a novel drug aimed at protecting donor organs during the period between removal of the organ and transplantation. If successful, these treatments have the potential to markedly increase the numbers of organ transplants and to improve the outcomes for recipients of these transplants. In the Australian and New Zealand setting, a 25% increase in the number of donor organs would results in approximately 220 more people per year receiving these life-saving operations.Read moreRead less
Global Data Mapping And Evaluation Of Needs, Capacities And Benchmarks In Organ Donation And Transplantation: Informing Effective Local And International Health Policy To Better Meet The Needs Of Patients
Funder
National Health and Medical Research Council
Funding Amount
$318,575.00
Summary
Global shortages of donor organs limit the provision of reliable and equitable access to solid organ transplantation. As a result, many are excluded from waiting lists, others deteriorate whilst awaiting transplantation, and some seek to purchase the needed organ. Countries have a responsibility to provide transplantation services sufficient to meet population need. This project evaluates international data for key interventions that may impact on waitlisting, donation and transplant practices.