Methane Admixture Protects Liver Mitochondria and Improves Graft Function after Static Cold Storage and Reperfusion

Abstract

Mitochondria are targets of cold ischemia-reperfusion (IR), the major cause of cell damage during static cold preservation of liver allografts. The bioactivity of methane (CH4) has recently been recognized in various hypoxic and IR conditions as having influence on many aspects of mitochondrial biology. We therefore hypothesized that cold storage of liver grafts in CH4-enriched preservation solution can provide an increased defence against organ dysfunction in a preclinical rat model of liver transplantation. Livers were preserved for 24 h in cold histidine–tryptophan–ketoglutarate (HTK) or CH4-enriched HTK solution (HTK-CH4) (n = 24 each); then, viability parameters were monitored for 60 min during normothermic isolated reperfusion and perfusate and liver tissue were collected. The oxidative phosphorylation capacity and extramitochondrial Ca2+ movement were measured by high resolution respirometry. Oxygen and glucose consumption increased significantly while hepatocellular damage was decreased in the HTK-CH4 grafts compared to the HTK group. Mitochondrial oxidative phosphorylation capacity was more preserved (128.8 ± 31.5 pmol/s/mL vs 201.3 ± 54.8 pmol/s/mL) and a significantly higher Ca2+ flux was detected in HTK-CH4 storage (2.9 ± 0.1 mV/s) compared to HTK (2.3 ± 0.09 mV/s). These results demonstrate the direct effect of CH4 on hepatic mitochondrial function and extramitochondrial Ca2+ fluxes, which may have contributed to improved graft functions and a preserved histomorphology after cold IR.

Assessment of Mitochondrial Respiration During Hypothermic Storage of Liver Biopsies Following Normothermic Machine Perfusion

“…The first key difference between these experiments is that livers analyzed in the present study have variable and notably longer cold ischemic times and have undergone reperfusion in the form of NMP, while in the previous study no machine perfusion was applied. This finding is in line with a recent study of Horváth et al [ 22 ]. They investigated the effect of prolonged CIT and subsequent normothermic isolated perfusion on mitochondrial function in DCD rat livers.…”

Cellular ROS and Antioxidants: Physiological and Pathological Role

“…In this Special Issue, Keppler et al [57] showed the capability of eukaryotic cells to synthesize CH4 via a radical-driven process. In addition, Horváth et al [58] demonstrated that although CH4 is synthesized in a radical-dependent way, it protects mitochondrial function and maintains Ca 2+ homeostasis. These data suggest that antioxidants can affect physiological CH4-mediated signaling.…”

Influence of cardioplegic solution on the incidence of AKI after CABG procedure: del Nido cardioplegia versus HTK solution: insight of KDIGO criteria

“…Furthermore, DN solutions lack calcium and are administered in a ratio of four parts crystalloid to one part blood [22]. Notably, the perfusion volume of HTK solution during CABG procedures is higher (2000ml vs. 1000ml) compared to DN solution, resulting in sodium and calcium levels below the normal range for the HTK group and within normal limits for the DN group [23].…”