Recovery of Warm Ischemic Rat Liver Grafts by Normothermic Extracorporeal Perfusion

Abstract

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.

Comparing Normothermic Machine Perfusion Preservation With Different Perfusates on Porcine Livers From Donors After Circulatory Death

“…These findings are important for several reasons. First, NMP is rapidly becoming the subject of preclinical and clinical research (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Second, different research groups have used various perfusion protocols but none have compared their efficacy.…”

“…Oxygen consumption (VO 2 ) was calculated using partial pressure of oxygen , hemoglobin saturation and blood flow, as specified by the formula described by Tolboom et al (15). The volume of bile production was recorded.…”

“…Normothermic machine perfusion (NMP) is a preservation technology with potential to prevent both ischemic injury and the deleterious effect of cold temperatures by perfusing organs with a warm oxygenated perfusion solution. Numerous studies have demonstrated the advantage of NMP over CS in the preservation of DCD livers (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), suggesting that NMP may greatly benefit the practice of liver transplantation. conducted using whole blood (WB) (9)(10)(11)(19)(20)(21).…”

Perfusion device for liver preservation ex vivo before transplantation: first experimental study

“…Поскольку пере садка печени является «хирургией одного шанса», то повышаются требования к методам верификации качества трансплантата перед операцией. Мини мизация нежелательных изменений в донорском органе могла бы быть достигнута за счет создания перфузионных устройств, с помощью которых воз можно проведение искусственного кровообраще ния для селекции, «лечения» и поддержания жиз неспособности in situ и ex vivo [4,6,7,10,12,13].…”

Infrahepatic cavocavostomy: Expanding the armamentarium for the liver transplant surgeon

“…Gong et al 13 reported that pig livers undergoing normothermic machine perfusion were significantly more viable than those stored in cold histidine-tryptophan-ketoglutarate solution. In a rat model, Tolboom et al 14 found that normothermic liver perfusion optimized the preservation of DCD livers.…”