For the last five decades, transplantation has been firmly set in the ice age. Cold perfusion and preservation have underpinned organ recovery and have been key to the current success of organ transplantation.
The growing demand for transplantation has led to a rapid increase in the utilization of extended criteria donors. In many countries, donation after circulatory death (DCD; from all Maastricht categories) has increased exponentially and now represents 40% to 50% of the transplant activity. However, the use of organs from these donors has come at a price—an increased risk of graft failure and complications. Despite refinements in definition and acceptance criteria, DCD donation remains associated with a lower organ recovery and poorer outcomes.
In an effort to improve the outcomes and allow further expansion of the organ pool, there has been a renewed interest in normothermic perfusion and preservation (1). This was seen as a way to minimize the detrimental effects of warm and cold ischemia, reduce the preservation injury, preserve the metabolic function, and allow a period of organ assessment before transplantation, in the donor as well as during organ storage.
The successful implementation of uncontrolled DCD donation and transplant programs in Spain has been intrinsically linked with the use of normothermic regional perfusion (NRP). Used as a bridge between asystole and organ retrieval, NRP led to an increase in organ recovery with excellent clinical outcomes (2). The expansion of NRP concept to controlled DCD donation was a natural progression and perhaps, not surprisingly, achieved similar results in terms of organ recovery rates and clinical outcomes (3). However, the common denominator in these studies has been the ability to institute donor treatment and vascular cannulation before death in DCD III or a continuation of organ preservation maneuvers, such as ventilation and cardiac massage, following death in uncontrolled DCD.
In this context, the paper by Butler et al. (4) published in this issue of Transplantation adds new evidence supporting a normothermic approach to organ recovery in controlled DCD donation. The authors established an extracorporeal circuit and perfused the abdominal organs for 2 hr before removal and cold storage. The use of NRP appeared to ameliorate the ischemic injury and replenished the ATP reserves, leading to increased organ recovery rates compared to standard controlled DCD, with good early function. However, the exact mechanisms of action and the extent of NRP benefit remain to be elucidated.
DCD organ assessment is notoriously difficult and relies mainly on surgeons’ experience. As a consequence, the rate of DCD organ recovery, especially for extrarenal organs, remains low. However, this study suggests that one of the main advantages of NRP is the ability to assess organ function and the extent of organ damage following circulatory arrest. Although the most appropriate markers for organ assessment remain to be confirmed by larger studies, the implications for organ recovery are noteworthy. NRP may allow for a reduction in organ discard rates and potentially lead to an increase in organ recovery and utilization beyond the currently accepted criteria, based on molecular and biochemical markers available at the time of retrieval. Furthermore, this approach could set the stage for organ modulation and reconditioning, opening new and exciting prospects in translational research and clinical practice.
This study also sets a new landmark in the DCD donor treatment saga. The current legislation in the UK prohibits any pre-mortem interventions (i.e., heparinization or vascular cannulation), which many believe would reduce the risk of intravascular thrombosis and the incidence of ischemia-related damage to the transplanted organs. Butler et al. (4) question this argument, suggesting that these interventions may not be required and do not preclude re-establishing oxygenated warm perfusion to the abdominal compartment and successful subsequent organ recovery.
Although this paper focuses primarily on the technical aspects of NRP, the limited outcome data provided are highly encouraging and complement the positive outcome reports of ex situ normothermic organ preservation in liver, kidney, heart, and lung transplantation (5). It is conceivable that with all these emerging novel technologies, the future of organ retrieval and preservation will be normothermic, but the road from aspiration to routine clinical implementation requires more than just a series of technical exercises.
In many ways, we are on the brink of a revolution in transplantation and the future may look very different from today. However, there are many more questions that need answered and the next 5 years will be crucial in clarifying the role of these technologies in providing more and better organs for transplantation.
1. Brockmann J, Reddy S, Coussios C, et al. Normothermic perfusion: a new paradigm for organ preservation. Ann Surg
2009; 250: 1.
2. Fondevila C, Hessheimer AJ, Ruiz A, et al. Liver transplant using donors after unexpected cardiac death: novel preservation protocol and acceptance criteria. Am J Transplant
2007; 7: 1849.
3. Magliocca JF, Magee JC, Rowe SA, et al. Extracorporeal support for organ donation after cardiac death effectively expands the donor pool. The Journal of trauma
2005; 58: 1095.
4. Butler AJ, Randle LV, Watson CJE. Normothermic regional perfusion for donation after circulatory death without prior heparinisation. Transplanation
5. Cypel M, Yeung JC, Liu M, et al. Normothermic ex vivo lung perfusion in clinical lung transplantation. N Engl J Med
2011; 364: 1431.