Introduction: The predominate issue in transplantation today is the inadequate supply of suitable
organs for an increasing number of patients on the transplant waiting lists. In efforts to address this
demand there has been an increasing use of expanded-criteria and donation-after-cardiac death
donor kidneys and pancreases, however these organs are at higher risk for reperfusion injury.
Advances in organ preservation thus need to focus on techniques to assess and optimise organ
viability prior to transplantation.
Methods: This research focuses on organ viability assessment during preservation using rapid
sampling micro-dialysis (rsMD); preconditioning organs with novel endothelial localising anticoagulants
to prevent micro-vascular thrombotic complications; development of both novel
hypothermic machine perfusion (HMP) solutions to minimise reperfusion injury, and HMP strategies
that offer superior preservation of organ integrity compared to static cold storage (SCS). Using HMP
and normothermic-reperfusion models of porcine and human kidney and pancreatic grafts, this
project has investigated strategies addressing these themes.
Results: rsMD can successfully provide detailed real-time information on tissue and organ viability
during both SCS and HMP. Pre-conditioning grafts with novel localising anticoagulant proteins has
been successful in ameliorating disturbances in macro and micro-vascular perfusion and graft
microcvascular thrombosis, processes which play key roles in reperfusion injury and organ
dysfunction. Separately the application of a novel adenosine/lidocaine based preservation solution
in renal HMP preservation can potentially ameliorate reperfusion injury seen using conventional
solutions. Post-ischaemic HMP reconditioning has been investigated in the context of recovering
organs with an extreme period of SCS which may be a potential option to expand donor organ pools.
Finally models of pancreatic HMP have been successfully established, opening the potential for
organ viability assessment and optimization.
Conclusion: This research has been successful in its overall objective to develop novel translational
strategies that have high potential for clinical implementation. In doing so the goal would be to
enable an expansion of the pool of acceptable donor organs by improving the methods used to
determine and optimise their viability, specifically more effective preservation techniques and by
addressing specific post-operative complications through graft preconditioning.