Project title

Endothelin Blockade in an Ovine Model of Brainstem Death (BD) using Ex-Vivo Lung Perfusion (EVLP)

Researchers

Connie Boon, Kristopher Skeggs, Jonathan Peter, Anil Prabhu, Lachlan Marshall, Sara Diab, Obonyo Gikenyi chafatso and John Fraser


Background


Brain-stem dead donors are the main source of lung grafts for transplantation to treat advanced stage lung disease. However, the complication of brain injury and death is complex and resulting in release of compounds which leads to haemodynamic, neurogenic and hormonal changes in the donor and jeopardise vital organ function and thereby associated with poorer graft function in the recipient. The damage caused by brain death is much greater in the lungs than is seen in other organs and only 20% of the multi-organ donors have lungs suitable for transplantation. Strategies for the management of organ donors after brain stem death remains to be investigated so that the functional integrity of potentially transplantable organs is maintained

Research Plan


Our previous study demonstrated the release of endothelin-1compound leads to lung injury in animal models of brain death and that endothelin blocker could be used to reduce its potential risk. Application of Ex-Vivo Lung Perfusion (EVLP) is widely employed into clinical therapeutics to allow the lungs to recover from brain death injury and also to monitor lung function parameters prior to transplantation. We further investigate whether the combination of endothelin antagonist administration and EVLP in ex-vivo model of brain death in the sheep to improve graft function while avoiding the potentially negative effects of this drug on other transplantable organs in the donor. With, this study may then further address the shortage of organs, increasing the quality and quantity of lungs available for transplantation.


Publications


Watts, R. P. et al. Novel 24-h ovine model of brain death to study the profile of the endothelin axis during cardiopulmonary injury. Intensive Care Med Exp 3, 31 (2015).

Sutherland, A. J. et al. The endothelin axis and gelatinase activity in alveolar macrophages after brain-stem death injury: a pilot study. J Heart Lung Transplant 26, 1040-1047 (2007).