Normothermic Perfusion

Brockmann, Jens; Reddy, Srikanth; Coussios, Constantin C.; Pigott, David; Guirriero, Dino; Hughes, David; Morovat, Alireza; Roy, Debabrata; Winter, Lucy; Friend, Peter J.

doi:10.1097/sla.0b013e3181a63c10

Cited by 263 publications

(87 citation statements)

References 34 publications

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“…While simplicity and minimal risk have driven the development of hypothermic systems, normothermic machine perfusion has sparked interest in the prospect of an ex vivo organ with close to normal physiology that opens up the opportunity for intervention, recovery, and viability testing (14,49). The complexity and associated risk have delayed clinical implementation and have even veered groups away.…”

Section: Discussionmentioning

confidence: 99%

Subnormothermic Machine Perfusion for Ex Vivo Preservation and Recovery of the Human Liver for Transplantation

Bruinsma

Yeh

Özer

et al. 2014

American Journal of Transplantation

177

173

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To reduce widespread shortages, attempts are made to use more marginal livers for transplantation. Many of these grafts are discarded for fear of inferior survival rates or biliary complications. Recent advances in organ preservation have shown that ex vivo subnormothermic machine perfusion has the potential to improve preservation and recover marginal livers pre- transplantation. To determine the feasibility in human livers, we assessed the effect of 3 hours of oxygenated subnormothermic machine perfusion (21 °C) on seven livers discarded for transplantation. Biochemical and microscopic assessment revealed minimal injury sustained during perfusion. Improved oxygen uptake (1.30 [1.11–1.94] to 6.74 [4.15–8.16] mL O2/min.kg liver), lactate levels (4.04 [3.70–6.00] to 2.29 [1.20–3.42] mmol/L) and adenosine triphosphate content (45.0 [70.6–87.5] pre-perfusion to 167.5 [151.5–237.2] pmol/mg after perfusion) were observed. Liver function, reflected by urea, albumin and bile production was seen during perfusion. Bile production increased and the composition of bile (bile salts/phospholipid ratio, pH and bicarbonate concentration) became more favorable. In conclusion, ex vivo subnormothermic machine perfusion effectively maintains liver function with minimal injury and sustains or improves various hepatobiliary parameters post-ischemia.

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Section: Discussionmentioning

confidence: 99%

Subnormothermic Machine Perfusion for Ex Vivo Preservation and Recovery of the Human Liver for Transplantation

Bruinsma

Yeh

Özer

et al. 2014

American Journal of Transplantation

177

173

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“…During the past decade, machine perfusion of donor livers has received increasing attention as a tool to improve organ preservation and improve outcome after transplantation [5], [6], [7], [8], [9]. Several experimental studies have shown superiority of machine perfusion compared to static cold storage with respect to reduction of ischemia/reperfusion (IR) injury [10], [11], [12].…”

Section: Introductionmentioning

confidence: 99%

Criteria for Viability Assessment of Discarded Human Donor Livers during Ex Vivo Normothermic Machine Perfusion

et al. 2014

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Although normothermic machine perfusion of donor livers may allow assessment of graft viability prior to transplantation, there are currently no data on what would be a good parameter of graft viability. To determine whether bile production is a suitable biomarker that can be used to discriminate viable from non-viable livers we have studied functional performance as well as biochemical and histological evidence of hepatobiliary injury during ex vivo normothermic machine perfusion of human donor livers. After a median duration of cold storage of 6.5 h, twelve extended criteria human donor livers that were declined for transplantation were ex vivo perfused for 6 h at 37°C with an oxygenated solution based on red blood cells and plasma, using pressure controlled pulsatile perfusion of the hepatic artery and continuous portal perfusion. During perfusion, two patterns of bile flow were identified: (1) steadily increasing bile production, resulting in a cumulative output of ≥30 g after 6 h (high bile output group), and (2) a cumulative bile production <20 g in 6 h (low bile output group). Concentrations of transaminases and potassium in the perfusion fluid were significantly higher in the low bile output group, compared to the high bile output group. Biliary concentrations of bilirubin and bicarbonate were respectively 4 times and 2 times higher in the high bile output group. Livers in the low bile output group displayed more signs of hepatic necrosis and venous congestion, compared to the high bile output group. In conclusion, bile production could be an easily assessable biomarker of hepatic viability during ex vivo machine perfusion of human donor livers. It could potentially be used to identify extended criteria livers that are suitable for transplantation. These ex vivo findings need to be confirmed in a transplant experiment or a clinical trial.

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“…For the liver, the main debate over machine perfusion relates to three separate approaches, differing in perfusate temperature and the degree of oxygenation: normothermic, subnormothermic and hypothermic liver perfusion. While normothermic machine perfusion (NMP) closely simulates in vivo conditions and therefore needs oxygenated diluted blood and nutritional compounds as perfusate [7–9], subnormothermic machine perfusion (SNMP) and hypothermic machine perfusion (HMP) rely on the physically dissolved oxygen in a blood-free perfusate at temperatures of 20-25 °C (subnormothermic) [10, 11] or 2-10 ° (hypothermic) [12, 13]. …”

Section: Introductionmentioning

confidence: 99%

Hypothermic Oxygenated Liver Perfusion: Basic Mechanisms and Clinical Application

2015

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Dynamic preservation strategies such as hypothermic machine perfusion are increasingly discussed to improve liver graft quality before transplantation. This review summarizes current knowledge of this perfusion technique for liver preservation. We discuss optimization of perfusion conditions and current strategies to assess graft quality during cold perfusion. Next, we provide an overview of possible pathways of protection from ischemia-reperfusion injury. Finally, we report on recent clinical applications of human hypothermic machine liver perfusion.

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Normothermic Perfusion

Cited by 263 publications

References 34 publications

Subnormothermic Machine Perfusion for Ex Vivo Preservation and Recovery of the Human Liver for Transplantation

Subnormothermic Machine Perfusion for Ex Vivo Preservation and Recovery of the Human Liver for Transplantation

Criteria for Viability Assessment of Discarded Human Donor Livers during Ex Vivo Normothermic Machine Perfusion

Hypothermic Oxygenated Liver Perfusion: Basic Mechanisms and Clinical Application

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