Can adenine nucleotides predict primary nonfunction of the human liver homograft?

Hamamoto, Isao; Takaya, Shunichi; Todo, Satoru; Bronsther, Oscar; Fujita, Shiro; Gulik, Thomas M. Van; Nakamura, Kenjiro; Irish, William; Starzl, Thomas E.

doi:10.1007/bf00336468

Cited by 17 publications

(4 citation statements)

References 23 publications

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“…Kamiike et al, found that not the pre, but the postreperfusion ATP levels were predictive of transplant success 14 . Looking at primary nonfunction as an outcome measure Hamamoto et al, 24 also found ATP levels to be predictive when measured at ~1.5 hours after reperfusion, in line with our findings.…”

Section: Discussionsupporting

confidence: 91%

Peritransplant Energy Changes and Their Correlation to Outcome After Human Liver Transplantation

et al. 2017

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Background The ongoing shortage of donor livers for transplantation and the increased use of marginal livers necessitate the development of accurate pretransplant tests of viability. Considering the importance energy status during transplantation, we aimed to correlate peritransplant energy cofactors to posttransplant outcome and subsequently model this in an ex vivo setting. Methods Sequential biopsies were taken from 19 donor livers postpreservation, as well as 30 min after portal venous (PVR) and hepatic arterial reperfusion (HAR) and analyzed by LC-MS for energetic cofactors (ATP/ADP/AMP, NADH/NAD+, NADPH/NADP+, FAD+, GSSG/GSH). Energy status was correlated to posttransplant outcome. In addition, 4 discarded human DCD livers were subjected to ex vivo reperfusion, modeling reperfusion injury and were similarly analyzed for energetic cofactors. Results A rapid shift towards higher energy adenine nucleotides was observed following clinical reperfusion, with a 2.45-, 3.17- and 2.12-fold increase in ATP:ADP, ATP:AMP and energy charge (EC) after PVR, respectively. Seven of the 19 grafts developed early allograft dysfunction (EAD). Correlation with peritransplant cofactors revealed a significant difference in EC between EAD and normal functioning grafts (0.09 vs. 0.31, P<0.05). In the simulated reperfusion model, a similar trend in adenine nucleotide changes was observed. Conclusion A preserved energy status appears critical in the peritransplant period. Levels of adenine nucleotides change rapidly following reperfusion and ratios of ATP/ADP/AMP following reperfusion are significantly correlated to graft function. Using these markers as a viability test in combination with ex vivo reperfusion may provide a useful predictor of outcome that incorporates donor, preservation and reperfusion factors.

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Section: Discussionsupporting

confidence: 91%

Peritransplant Energy Changes and Their Correlation to Outcome After Human Liver Transplantation

et al. 2017

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“…There is growing evidence showing that hepatic ATP content before transplantation and recovery of the energy status during reperfusion is positively correlated with favorable posttransplant outcome 4 25 26 . In clinical studies, a correlation between postpreservation 27 or postreperfusion 28 29 30 ATP levels and primary liver graft function was suggested. The metabolomic comparison between the ischemic and the perfused liver in this study shows a considerable recovery of energy metabolism during SNMP.…”

Section: Discussionmentioning

confidence: 99%

Metabolic profiling during ex vivo machine perfusion of the human liver

Bruinsma

Sridharan

Weeder

et al. 2016

Sci Rep

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As donor organ shortages persist, functional machine perfusion is under investigation to improve preservation of the donor liver. The transplantation of donation after circulatory death (DCD) livers is limited by poor outcomes, but its application may be expanded by ex vivo repair and assessment of the organ before transplantation. Here we employed subnormothermic (21 °C) machine perfusion of discarded human livers combined with metabolomics to gain insight into metabolic recovery during machine perfusion. Improvements in energetic cofactors and redox shifts were observed, as well as reversal of ischemia-induced alterations in selected pathways, including lactate metabolism and increased TCA cycle intermediates. We next evaluated whether DCD livers with steatotic and severe ischemic injury could be discriminated from ‘transplantable’ DCD livers. Metabolomic profiling was able to cluster livers with similar metabolic patterns based on the degree of injury. Moreover, perfusion parameters combined with differences in metabolic factors suggest variable mechanisms that result in poor energy recovery in injured livers. We conclude that machine perfusion combined with metabolomics has significant potential as a clinical instrument for the assessment of preserved livers.

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“…The homogenates were centrifuged for 10 min at 10 000 g at 4°C with a refrigerated centrifuge (High‐Speed Micro Refrigerated Centrifuge, MR‐150; Tomy, Tokyo, Japan). The pH of the supernatant was adjusted to 4–6 with 69% K 2 CO 3 solution and the tissue was centrifuged again for 10 min at 10 000 g. Supernatant was measured for ATP by high‐performance liquid chromatography (HPLC), using the method described by Hamamoto et al8…”

Section: Methodsmentioning

confidence: 99%

Protective effects of d-allose against ischemia reperfusion injury of the rat liver

Hossain

Izuishi

Maeta

2003

Journal of Hepato-Biliary-Pancreatic Surgery

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Can adenine nucleotides predict primary nonfunction of the human liver homograft?

Cited by 17 publications

References 23 publications

Peritransplant Energy Changes and Their Correlation to Outcome After Human Liver Transplantation

Peritransplant Energy Changes and Their Correlation to Outcome After Human Liver Transplantation

Metabolic profiling during ex vivo machine perfusion of the human liver

Protective effects of d-allose against ischemia reperfusion injury of the rat liver

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