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Presenter: Gayathri, Kumarasinghe, Darlinghurst, Australia
Authors: Gayathri Kumarasinghe, Ling Gao, Mark Hicks, Aoife Doyle, Padmashree Rao, Arjun Iyer, Alisdair Watson, Andrew Jabbour, Christopher Hayward, Peter Macdonald
â€˜Pharmacological conditioningâ€™ improves recovery of hearts from brain dead rats after prolonged hypothermic storage
Gayathri Kumarasinghe1, Ling Gao1, Mark Hicks1, Aoife Doyle1, Padmashree Rao1, Arjun Iyer1, Alisdair Watson1, Andrew Jabbour1, Christopher Hayward1, Peter Macdonald1
1Cardiac Physiology and Transplantation Laboratory, Victor Chang Cardiac Research Institute, Sydney, Australia
Aim Cold storage of hearts from brain dead (BD) donors is still the mainstay in cardiac transplantation, however ischaemia-reperfusion injury (IRI) and primary graft failure (PGF) are significant disadvantages. We found that the addition of ‘conditioning’ agents–Glyceryl trinitrate (GTN), Erythropoietin (EPO) and Zoniporide (ZON) to standard preservation solutions attenuates IRI in rat hearts[2-4]. We aimed to test their efficacy under conditions of BD and prolonged cold storage.
Methods Male Lewis rats were subjected to BD by inflation of a subdural embolectomy catheter. Invasive haemodynamic changes were measured in BD and sham groups. Cardiac output (CO) was then assessed on an isolated working heart model (IWHM) and hearts arrested and preserved in 4°C using either Celsior preservation solution for 1, 3 or 6 hours, or Celsior supplemented with GTN, EPO and ZON for 3 or 6 hours (n=6 each sub-group). Post-storage CO was reassessed on an IWHM.
Results Hearts from BD rats showed inferior recovery of CO compared with shams. Supplementing Celsior preservation solution with GTN+EPO+ZON significantly improved CO in hearts from BD rats.
Conclusion Pharmacological conditioning agents GTN, EPO & ZON significantly improve recovery of hearts from BD rats after prolonged cold storage. This shows promising potential for application in clinical cardiac transplantation.
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