Ex Vivo Normothermic Machine Perfusion Is Safe, Simple, and Reliable

Nassar, Ahmed; Liu, Qiang; Farias, Kevin; D’Amico, Giuseppe; Tom, Cynthia M.; Grady, Patrick; Bennett, Ana E.; Uso, Teresa Diago; Eghtesad, Bijan; Kelly, D. G.; Fung, John J.; Abu‐Elmagd, Kareem; Miller, Charles M.; Quintini, Cristiano

doi:10.1177/1553350614528383

Cited by 60 publications

(74 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the past, we and others have demonstrated that warm perfusion (subnormothermic or normothermic) on its own improves liver grafts during the preservation period. In 2014, we demonstrated in a donation after circulatory death (DCD) pig LT model that warm perfusion improves the preservation of ECs and reduces bile duct injury .…”

Section: Discussionmentioning

confidence: 97%

Anti‐inflammatory signaling during ex vivo liver perfusion improves the preservation of pig liver grafts before transplantation

et al. 2016

View full text Add to dashboard Cite

Normothermic ex vivo liver perfusion (NEVLP) improves graft preservation by avoiding cold ischemia injury. We investigated whether the protective effects of NEVLP can be further improved by applying strategies targeted on reducing the activation of proinflammatory cytokines during perfusion. Livers retrieved under heart-beating conditions were perfused for 4 hours. Following the preservation period, a pig liver transplantation was performed. In group 1 (n = 5), anti-inflammatory strategies (alprostadil, n-acetylcysteine, carbon monoxide, sevoflurane, and subnormothermic temperature [33°C]) were applied. This was compared with a perfused control group (group 2) where livers (n = 5) were perfused at 37°C without anti-inflammatory agents, similar to the setup used in current European clinical trials, and to a control group preserved with static cold storage (group 3). During 3-day follow-up, markers of reperfusion injury, bile duct injury, and liver function were examined. Aspartate aminotransferase (AST) levels during perfusion were significantly lower in the study versus control group at 1 hour (52 ± 6 versus 162 ± 86 U/L; P = 0.01), 2 hours (43 ± 5 versus 191 ± 111 U/L; P = 0.008), and 3 hours (24 ± 16 versus 218 ± 121 U/L; P = 0.009). During perfusion, group 1 versus group 2 had reduced interleukin (IL) 6, tumor necrosis factor α, and galactosidase levels and increased IL10 levels. After transplantation, group 1 had lower AST peak levels compared with group 2 and group 3 (1400 ± 653 versus 2097 ± 1071 versus 1747 ± 842 U/L; P = 0.47) without reaching significance. Bilirubin levels were significantly lower in group 1 versus group 2 at day 1 (3.6 ± 1.5 versus 6.60 ± 1.5 μmol/L; P = 0.02) and 3 (2 ± 1.1 versus 9.7 ± 7.6 μmol/L; P = 0.01). A trend toward decreased hyaluronic acid, as a marker of improved endothelial cell function, was observed at 1, 3, and 5 hours after reperfusion in group 1 versus group 2. Only 1 early death occurred in each group (80% survival). In conclusion, addition of anti-inflammatory strategies further improves warm perfused preservation. Liver Transplantation 22 1573-1583 2016 AASLD.

show abstract

Section: Discussionmentioning

confidence: 97%

Anti‐inflammatory signaling during ex vivo liver perfusion improves the preservation of pig liver grafts before transplantation

et al. 2016

View full text Add to dashboard Cite

show abstract

“…All livers were flushed with 1 L of normal saline at 21°C through hepatic artery (HA) and portal vein (PV) cannulations to remove histidine tryptophan ketoglutarate solution or University of Wisconsin solution. All livers underwent 24 hours of NMP using the perfusion system previously reported . The perfusion system consisted of an organ receptacle, centrifugal pump, roller pump, oxygenator, and heat exchanger.…”

Section: Methodsmentioning

confidence: 99%

Lipid metabolism and functional assessment of discarded human livers with steatosis undergoing 24 hours of normothermic machine perfusion

et al. 2018

Self Cite

View full text Add to dashboard Cite

Normothermic machine perfusion (NMP) is an emerging technology to preserve liver allografts more effectively than cold storage (CS). However, little is known about the effect of NMP on steatosis and the markers indicative of hepatic quality during NMP. To address these points, we perfused 10 discarded human livers with oxygenated NMP for 24 hours after 4-6 hours of CS. All livers had a variable degree of steatosis at baseline. The perfusate consisted of packed red blood cells and fresh frozen plasma. Perfusate analysis showed an increase in triglyceride levels from the 1st hour (median, 127 mg/dL; interquartile range [IQR], 95-149 mg/dL) to 24th hour of perfusion (median, 203 mg/dL; IQR, 171-304 mg/dL; P = 0.004), but tissue steatosis did not decrease. Five livers produced a significant amount of bile (≥5 mL/hour) consistently throughout 24 hours of NMP. Lactate in the perfusate cleared to <3 mmol/L in most livers within 4-8 hours of NMP, which was independent of bile production rate. This is the first study to characterize the lipid profile and functional assessment of discarded human livers at 24 hours of NMP. Liver Transplantation 24 233-245 2018 AASLD.

show abstract

“…Although graft viability can be assessed in all machine perfusion setups, NMP theoretically offers the best context to sample the perfusate for injury markers (for example, ALT, lactate), since liver metabolism is maintained at a physiological level and additional injury by warm reperfusion is avoided. In a pig model of liver preservation, 10 h of NMP proved superior to SCS, as determined by liver injury parameters (AST release, bile production) as well as liver histology after 24 h of reperfusion (89). In a similar experimental model, SCS elicited severe biliary necrosis, compared with only mild biliary damage after NMP (90).…”

Section: Clinical Status Quo Of Organ Cooling In Liver Surgery Liver mentioning

confidence: 81%

Protective Mechanisms of Hypothermia in Liver Surgery and Transplantation

Olthof

Reiniers

Dirkes

et al. 2015

Mol Med

View full text Add to dashboard Cite

Hepatic ischemia/reperfusion (I/R) injury is a side effect of major liver surgery that often cannot be avoided. Prolonged periods of ischemia put a metabolic strain on hepatocytes and limit the tolerable ischemia and preservation times during liver resection and transplantation, respectively. In both surgical settings, temporarily lowering the metabolic demand of the organ by reducing organ temperature effectively counteracts the negative consequences of an ischemic insult. Despite its routine use, the application of liver cooling is predicated on an incomplete understanding of the underlying protective mechanisms, which has limited a uniform and widespread implementation of liver-cooling techniques. This review therefore addresses how hypothermia-induced hypometabolism modulates hepatocyte metabolism during ischemia and thereby reduces hepatic I/R injury. The mechanisms underlying hypothermia-mediated reduction in energy expenditure during ischemia and the attenuation of mitochondrial production of reactive oxygen species during early reperfusion are described. It is further addressed how hypothermia suppresses the sterile hepatic I/R immune response and preserves the metabolic functionality of hepatocytes. Lastly, a summary of the clinical status quo of the use of liver cooling for liver resection and transplantation is provided.

show abstract

Ex Vivo Normothermic Machine Perfusion Is Safe, Simple, and Reliable

Abstract: Our study shows that NMP is safe, reliable, and provides superior graft preservation compared to CS in our DCD porcine model.

Cited by 60 publications

References 20 publications

Anti‐inflammatory signaling during ex vivo liver perfusion improves the preservation of pig liver grafts before transplantation

Anti‐inflammatory signaling during ex vivo liver perfusion improves the preservation of pig liver grafts before transplantation

Lipid metabolism and functional assessment of discarded human livers with steatosis undergoing 24 hours of normothermic machine perfusion

Protective Mechanisms of Hypothermia in Liver Surgery and Transplantation

Contact Info

Product

Resources

About