Opposite acute potassium and sodium shifts during transplantation of hypothermic machine perfused donor livers

Abstract

Liver transplantation is frequently associated with hyperkalemia, especially after graft reperfusion. Dual hypothermic oxygenated machine perfusion (DHOPE) reduces ischemia/reperfusion injury and improves graft function, compared to conventional static cold storage (SCS). We examined the effect of DHOPE on ex situ and in vivo shifts of potassium and sodium. Potassium and sodium shifts were derived from balance measurements in a preclinical study of livers that underwent DHOPE (n = 6) or SCS alone (n = 9), followed by ex situ normothermic reperfusion. Similar measurements were performed in a clinical study of DHOPE‐preserved livers (n = 10) and control livers that were transplanted after SCS only (n = 9). During DHOPE, preclinical and clinical livers released a mean of 17 ± 2 and 34 ± 6 mmol potassium and took up 25 ± 9 and 24 ± 14 mmol sodium, respectively. After subsequent normothermic reperfusion, DHOPE‐preserved livers took up a mean of 19 ± 3 mmol potassium, while controls released 8 ± 5 mmol potassium. During liver transplantation, blood potassium levels decreased upon reperfusion of DHOPE‐preserved livers while levels increased after reperfusion of SCS‐preserved liver, delta potassium levels were ‐0.77 ± 0.20 vs. +0.64 ± 0.37 mmol/L, respectively (P = .002). While hyperkalemia is generally anticipated during transplantation of SCS‐preserved livers, reperfusion of hypothermic machine perfused livers can lead to decreased blood potassium or even hypokalemia in the recipient.

Hypothermic oxygenated perfusion protects from mitochondrial injury before liver transplantation

“…For example, arctic ground squirrels tolerate hypoxia during arousal without subsequent development of relevant ischemia-reperfusion injury. Likewise, during hibernation, arterial oxygen saturation is significantly higher compared to euthermia [41] , and the ATP level is well preserved [42] , similarly to hypothermic oxygenated perfusion [ 30 , [43] , [44] , [45] , [46] , [47] , [48] , [49] ]. These findings were paralleled by the determination of the key role of complex I-derived oxidative stress in aging comparing different species with a short or long life span.…”

Hypothermic Oxygenated Machine Perfusion of Liver Grafts from Brain-Dead Donors

“…Improved hemodynamic stability upon graft reperfusion is consistently observed when dynamic preservation techniques – both normothermic and hypothermic machine perfusion - are employed and could be related to the reduction of ischemia-reperfusion injury, the washout of metabolites produced during ischemia and to the “vascular bed recruitment” effect of machine perfusion 17,45 . Recently, a paper from the Groningen group shed further insight on this topic by showing that HOPE-preserved liver grafts, as opposed to what is commonly observed after SCS, release potassium in the perfusate during machine perfusion and take up potassium upon reperfusion, preventing the development of the acute hyperkalemia that is frequently associated with severe PRS 51 . Severe post-reperfusion syndrome has been shown to be a marker of more severe ischemia-reperfusion injury and also to be associated with an increased rate of AKI after LT 52 .…”

Human Red Blood Cells as Oxygen Carriers to Improve Ex-Situ Liver Perfusion in a Rat Model

“…The improved glucose and lactate uptake, and the increased glycogen and ATP tissue content, further indicate an upregulated metabolic status in the BLOOD group. The reduced potassium uptake and significant increase of W/D ratio at the end of perfusion (compared to SCS) in DMEM group likely depends on a more severe liver damage [37]. Furthermore, the direct relation between DO 2 /VO˙ 2 and metabolic parameters suggests that the total amount of oxygen transported (DO 2 ) results in an increased ability to use oxygen (VO˙ 2 ) to generate energy (ATP) to sustain hepatocellular metabolism.…”