Interstitial Lactic Acidosis in the Graft During Organ Harvest, Cold Storage, and Reperfusion of Human Liver Allografts Predicts Subsequent Ischemia Reperfusion Injury

Ma, Salam; Murphy, Nick; Richards, DA; Wigmore, Stephen J.; Bramhall,; Ja, Buckels; Adams, David H.; Df, Mirza

doi:10.1097/01.tp.0000226234.76036.c1

Cited by 33 publications

(31 citation statements)

References 22 publications

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“…These findings are in agreement with both of our previous studies on total warm liver ischemia as well as studies done by other research groups [17,25,26] . Lactate levels in the normally perfused part of the liver were not affected by occlusion of another part of the liver, i.e.…”

Section: Discussionsupporting

confidence: 83%

Partial Liver Ischemia Is Followed by Metabolic Changes in the Normally Perfused Part of the Liver during Reperfusion

Kannerup

Grønbæk²,

Funch‐Jensen³

et al. 2010

Eur Surg Res

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Background: Temporary vascular in- and outflow occlusion is an effective technique for bleeding control during liver resection. However, occlusion can result in ischemia/reperfusion (I/R) injury to the liver. The aim of this study in a porcine model was to investigate the effect of in- and outflow occlusion of part of the liver on the metabolism of the normally perfused parenchyma of the same liver measured by microdialysis. Methods: Eight pigs underwent laparotomy. A microdialysis catheter was inserted into in the left and right part of the liver, respectively. Microdialysis samples were collected every 30 min. Occlusion of the left part of the liver was achieved for 60 min, followed by 5 h of reperfusion. Samples were analyzed for glucose, lactate, pyruvate and glycerol. Blood samples were drawn to determine standard liver and biochemical parameters. Results: Comparing the ischemic part of the liver with the normally perfused part, significant differences in the levels of lactate, pyruvate and glycerol were found. During reperfusion, similar and continuous decreases below baseline levels were observed for lactate and pyruvate in both the ischemic and normally perfused part of the liver. No significant changes in liver parameters or blood glucose levels were seen. Conclusions: Partial ischemia of the liver is without effects on metabolism in the normally perfused part. Metabolic changes in the ischemic part of the liver were reversible. However, partial liver ischemia was followed by similar continuous decreases in lactate and pyruvate levels in the whole liver, even though the ischemic insult was not detectable in transaminase levels.

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Section: Discussionsupporting

confidence: 83%

Partial Liver Ischemia Is Followed by Metabolic Changes in the Normally Perfused Part of the Liver during Reperfusion

Kannerup

Grønbæk²,

Funch‐Jensen³

et al. 2010

Eur Surg Res

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“…Metabolic substances (lactate, pyruvate, glucose, glycerol, urea, and glutamate) and mediators of inflammation (cytokines, chemokines, and complement activation products) could be sampled from the intercellular space in hepatic tissue by this method. In liver transplantation, high concentrations of intrahepatic lactate before reperfusion correlated with the magnitude of reperfusion injury . Poorly functioning liver grafts were associated with high lactate concentrations prior to reperfusion and complement activation as seen by C4d deposition detected by histological examination .…”

Section: Liver Transplantationmentioning

confidence: 96%

The Role of Complement in Liver Injury, Regeneration, and Transplantation

et al. 2019

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The liver is both an immunologically complex and a privileged organ. The innate immune system is a central player, in which the complement system emerges as a pivotal part of liver homeostasis, immune responses, and crosstalk with other effector systems in both innate and adaptive immunity. The liver produces the majority of the complement proteins and is the home of important immune cells such as Kupffer cells. Liver immune responses are delicately tuned between tolerance to many antigens flowing in from the alimentary tract, a tolerance that likely makes the liver less prone to rejection than other solid organ transplants, and reaction to local injury, systemic inflammation, and regeneration. Notably, complement is a double‐edged sword as activation is detrimental by inducing inflammatory tissue damage in, for example, ischemia–reperfusion injury and transplant rejection yet is beneficial for liver tissue regeneration. Therapeutic complement inhibition is rapidly developing for routine clinical treatment of several diseases. In the liver, targeted inhibition of damaged tissue may be a rational and promising approach to avoid further tissue destruction and simultaneously preserve beneficial effects of complement in areas of proliferation. Here, we argue that complement is a key system to manipulate in the liver in several clinical settings, including liver injury and regeneration after major surgery and preservation of the organ during transplantation.

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“…Microdialysis catheters are able to sample metabolic substances and inflammatory mediators directly from the organ of interest. We have found that ischemia can be detected as increased lactate levels and lactate/pyruvate ratios and that rejection can be detected as increased lactate and pyruvate levels with stable lactate/pyruvate ratios .…”

mentioning

confidence: 99%

Clinical experience with microdialysis catheters in pediatric liver transplants

et al. 2013

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Ischemic vascular complications and rejection occur more frequently with pediatric liver transplants versus adult liver transplants. Using intrahepatic microdialysis catheters, we measured lactate, pyruvate, glucose, and glycerol values at the bedside for a median of 10 days in 20 pediatric liver grafts. Ischemia (n 5 6), which was defined as a lactate level > 3.0 mM and a lactate/pyruvate ratio > 20, was detected without a measurable time delay with 100% sensitivity and 86% specificity. Rejection (n 5 8), which was defined as a lactate level > 2.0 mM and a lactate/pyruvate ratio < 20 lasting for 6 or more hours, was detected with 88% sensitivity and 45% specificity. With additional clinical criteria, the specificity was 83% without a decrease in the sensitivity. Rejection was detected at a median of 4 days (range 5 1-7 days) before alanine aminotransferase increased (n 5 5, P 5 0.11), at a median of 4 days (range 5 2-9 days) before total bilirubin increased 25% or more (n 5 7, P 5 0.04), and at a median of 6 days (range 5 4-11 days) before biopsy was performed (n 5 8, P 5 0.05). In conclusion, microdialysis catheters can be used to detect episodes of ischemia and rejection before current standard methods in pediatric liver transplants with clinically acceptable levels of sensitivity and specificity. The catheters were well tolerated by the children, and no major complications related to the catheters were observed.

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Interstitial Lactic Acidosis in the Graft During Organ Harvest, Cold Storage, and Reperfusion of Human Liver Allografts Predicts Subsequent Ischemia Reperfusion Injury

Abstract: Interstitial lactic acidosis in the donor allograft is associated with significant reperfusion injury on implantation.

Cited by 33 publications

References 22 publications

Partial Liver Ischemia Is Followed by Metabolic Changes in the Normally Perfused Part of the Liver during Reperfusion

Partial Liver Ischemia Is Followed by Metabolic Changes in the Normally Perfused Part of the Liver during Reperfusion

The Role of Complement in Liver Injury, Regeneration, and Transplantation

Clinical experience with microdialysis catheters in pediatric liver transplants

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