Abstract
BackgroundLiver donor shortages stimulate the development of strategies that incorporate damaged organs into the donor pool. Herein we present a simplified machine perfusion system without the need for oxygen carriers or temperature control, which we validated in a model of orthotopic liver transplantation.MethodsRat livers were procured and subnormothermically perfused with supplemented Williams E medium for 3 hours, then transplanted into healthy recipients (Fresh-SNMP group). Outcome was compared with static cold stored organs (UW-Control group). In addition, a rat liver model of donation after cardiac death was adapted using a 60-minute warm ischemic period, after which the grafts were either transplanted directly (WI group) or subnormothermically perfused and transplanted (WI-SNMP group).ResultsOne-month survival was 100% in the Fresh-SNMP and UW-Control groups, 83.3% in the WI-SNMP group and 0% in the WI group. Clinical parameters, postoperative blood work and histology did not differ significantly between survivors.ConclusionThis work demonstrates for the first time in an orthotopic transplantation model that ischemically damaged livers can be regenerated effectively using practical subnormothermic machine perfusion without oxygen carriers.
Highlights
Liver donor shortages stimulate the development of strategies that incorporate damaged organs into the donor pool
It follows that because hypothermic machine perfusion (HMP) is superior to SCS at temperatures where metabolism is slowed, a separate, perhaps mechanistic phenomenon contributes to this advantage [9,10]
The animals were divided into four groups: the UWControl group (n = 4, 3 hours at 4°C, SCS preservation and subsequent transplantation), the WI group (n = 4, 60 minutes at 34°C, warm ischemia and transplantation), the Fresh-subnormothermic machine perfusion (SNMP) group (n = 6, 3 hours of SNMP and transplantation) and the WI-SNMP group (n = 6, 60 minutes at 34°C, warm ischemia followed by 3 hours of SNMP and transplantation)
Summary
Liver donor shortages stimulate the development of strategies that incorporate damaged organs into the donor pool. In 2009, the waiting list mortality rate was 15% in the United States (approximately 1,500 patients), whereas the transplantation rate was about 38% (5,000 transplantations) [1] This shortage has driven scientific efforts to increase organ availability targeted at upgrading conventional storage methods (static cold storage (SCS) in University of Wisconsin (UW) solution) or employing graft optimization to allow for extension of donor criteria. The lower temperature decreases the fluidity of the plasma membrane, which can lead to cell lysis and increased enzyme leakage [8] It follows that because HMP is superior to SCS at temperatures where metabolism is slowed, a separate, perhaps mechanistic phenomenon contributes to this advantage [9,10]. Few studies have compared HMP with NMP in the same setting, NMP has been successful in regenerating warm ischemic grafts and preserving livers in rat and porcine models, proving its superiority over SCS [17,18,19,20,21,22,23,24]
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