Background Liver transplantation is currently the only established treatment for end-stage liver disease, but it is limited by a severe shortage of viable donor livers. Donors after cardiac death (DCD) are an untapped source that could significantly increase the pool of available livers. Preservation of these DCD livers by conventional static cold storage (SCS) is associated with an unacceptable risk of primary non-function and delayed graft failure. Normothermic extracorporeal liver perfusion (NELP) has been suggested as an improvement over SCS. Methods Livers recovered from male Lewis rats were subjected to 1hr of warm ischemia and preserved with 5hrs of SCS or NELP, and transplanted into syngeneic recipients. As additional controls, non-ischemic livers preserved with 6hrs of SCS or NELP and unpreserved ischemic livers were transplanted. Results Following NELP, ischemically damaged livers could be orthotopically transplanted into syngeneic recipients with 92% survival (N=13) after 4 weeks, which was comparable to control animals which received healthy livers preserved by SCS (N=9) or NELP (N=11) for 6hrs. On the other hand, animals from ischemia/SCS control group all died within 12hrs post-operatively (N=6). Similarly, animals that received ischemic livers without preservation all died within 24hrs after transplantation (N=6). Conclusions These results suggest that NELP has the potential to reclaim warm ischemic livers that would not be transplantable otherwise. The rat model in this study is a useful platform to further optimize NELP as a method of recovery and preservation of DCD livers.

Current techniques for the preservation of donor livers typically rely on cold temperatures (approximately 0-4 degrees C) to slow down metabolic processes. Recently, normothermic extracorporeal liver perfusion (NELP) has regained interest as a potentially promising approach for long-term liver preservation. Unlike cold-storage techniques, NELP attempts to maintain the liver in a near physiological environment, thus enabling normal metabolic and tissue repair processes to take place, which may help in the recovery of ischemically damaged and fatty donor livers, both of which represent significant untapped sources of donor livers. However, NELP is technically more complex than cold-storage techniques, and the lack of standardized small animal models limits its development. Here we describe a rat NELP system that is simple and cost-effective to run. We show that rat livers that underwent NELP for 6 h could be routinely transplanted into syngeneic recipient rats with excellent 1-month survival. During perfusion, the release of cytosolic enzymes, bile and urea production, and oxygen uptake rate could be readily monitored, thus providing a comprehensive picture of hepatic function before transplantation. This system will help in the optimization of NELP in several ways, such as for the improvement of perfusion conditions and the development of quantitative metabolic criteria for hepatic viability.