BACKGROUND: The mechanisms responsible for liver damage during cold storage are still not completely understood. We have investigated the role played by alterations of Na+ homeostasis in cell injury during cold hypoxia. METHODS: The changes in Na+ distribution were investigated in isolated rat hepatocytes stored at 4 degrees C under hypoxic conditions. RESULTS: Hepatocyte cold stored up to 72 hr in Krebs-Henseleit-Hepes buffer showed a progressive increase in intracellular Na+ content that preceded the loss of cell viability. Na+ accumulation and cell death were prevented using Na+-free, acidic (pH 6.5) or glycine-supplemented storage media. The Na+ ionophore monensin reverted the cytoprotection exerted by glycine and by the acidic medium, but not that given by Na+-free Krebs-Henseleit-Hepes. A low Na+ content was also important for the cytoprotection observed using University of Wisconsin solution. CONCLUSIONS: Na+ overload might contribute to liver graft injury occurring during cold storage.
BACKGROUND: The mechanisms responsible for liver damage during cold storage are still not completely understood. We have investigated the role played by alterations of Na+ homeostasis in cell injury during cold hypoxia. METHODS: The changes in Na+ distribution were investigated in isolated rat hepatocytes stored at 4 degrees C under hypoxic conditions. RESULTS: Hepatocyte cold stored up to 72 hr in Krebs-Henseleit-Hepes buffer showed a progressive increase in intracellular Na+ content that preceded the loss of cell viability. Na+ accumulation and cell death were prevented using Na+-free, acidic (pH 6.5) or glycine-supplemented storage media. The Na+ ionophore monensin reverted the cytoprotection exerted by glycine and by the acidic medium, but not that given by Na+-free Krebs-Henseleit-Hepes. A low Na+ content was also important for the cytoprotection observed using University of Wisconsin solution. CONCLUSIONS: Na+ overload might contribute to liver graft injury occurring during cold storage.