Calcium prevents loss of glutathione and reduces oxidative stress upon reperfusion in the perfused liver.

BACKGROUND Addition of 1.5 mM Ca2+ to the preservation solution (UW) during static cold rat liver preservation have been shown to improve liver function upon reperfusion. Effects of adding calcium to the perfusate during liver machine perfusion are yet not described. METHODS A recently developed model for rat liver machine perfusion (hypothermic oscillating oxygenated liver perfusion) was used to perfuse rat livers with calcium free modified UW solution (Group 1) or with modified UW + 2 mM CaCl2 (Group 2) for a period of 10 h (4 degrees C). In both experimental groups an acellular reperfusion at 37 degrees C with Ringer solution and 50 microM ferricytochrome c over a period of 90 min was performed. Liver and perfusate samples were taken before and after reperfusion to assess the cellular energy charge, metabolites, parameters of oxidative stress, cellular calcium, bile flow, enzyme release and TNF alpha. RESULTS Hypothermic perfusion with oxygenated calcium free modified UW solution resulted in depletion of cellular calcium and glutathione. Upon reperfusion bile function was inhibited in spite of a sufficiently reloaded energy charge and low LDH release. In contrast machine perfusion with modified UW solution +2 mM Ca2+ prevented the loss of both, cellular calcium and glutathione during the preservation period and led to sufficient bile flow and less release of superoxide anions upon reperfusion. CONCLUSIONS The loss of cellular calcium and glutathione during oxygenated machine liver perfusion appeared to be reducible by adding 2 mM Ca2+. Furthermore, upon reperfusion, livers with preserved cellular calcium demonstrated significantly lower oxidative stress and an improved liver function.