Abstract
BackgroundThe 110,000 patients currently on the transplant waiting list reflect the critical shortage of viable donor organs. However, a large pool of unused organs, from donors after cardiac death (DCD) that are disqualified because of extensive ischemic injury, may prove transplantable after machine perfusion treatment, fundamentally impacting the availability of treatment for end-stage organ failure. Machine perfusion is an ex-vivo organ preservation and treatment procedure that has the capacity to quantitatively evaluate and resuscitate cadaveric organs for transplantation.MethodsTo diagnose whether an organ was fresh or ischemic, an initial assessment of liver quality was conducted via dynamic discriminant analysis. Subsequently, to determine whether the organs were sufficiently viable for successful implantation, fitness indices for transplantation were calculated based on squared prediction errors (SPE) for fresh and ischemic livers.ResultsWith just three perfusate metabolites, glucose, urea and lactate, the developed MPLSDA model distinguished livers as fresh or ischemic with 90% specificity. The SPE analyses revealed that fresh livers with SPEF < 10.03 and WI livers with SPEWI < 3.92 yield successful transplantation with 95% specificity.ConclusionsThe statistical methods used here can discriminate between fresh and ischemic livers based on simple metabolic indicators measured during perfusion. The result is a predictive fitness index for transplantation of rat livers procured after cardiac death. The translational implications of this study are that any donor organ procured from controlled, but most especially from uncontrolled cardiac death donors, will be objectively assessed and its recovery monitored over time, minimizing the critical loss of otherwise viable organs.
Highlights
The 110,000 patients currently on the transplant waiting list reflect the critical shortage of viable donor organs
4,000 patients perish while waiting for a donor liver every year [3], while the estimated pool of livers from donors after cardiac death (DCD) with recoverable ischemic times of 30 – 60 minutes is on the order of 6,000 grafts per year [2]
Degree of ischemia and classification multi-way partial least squares discriminant analysis (MPLSDA) can classify a perfused graft as healthy or ischemic so that a decision can be made about the organ quality and eventually, on its fitness for transplantation
Summary
The 110,000 patients currently on the transplant waiting list reflect the critical shortage of viable donor organs. 4,000 patients perish while waiting for a donor liver every year [3], while the estimated pool of livers from donors after cardiac death (DCD) with recoverable ischemic times of 30 – 60 minutes is on the order of 6,000 grafts per year [2]. Preclinical studies with extracorporeal machine perfusion systems in porcine and murine models of DCD livers [5,6,7,8,9,10,11], including from our group [12,13,14], indicate that up to 60 minutes of warm ischemic damage can be successfully reversed, whereas static cold storage in preservation medium, the current clinical gold standard, exacerbates the damage and recipient animals do not survive. Research in machine perfusion systems is subsequently a very active field in donor organ recovery and preservation [15,16,17,18]
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