CHANGES IN CALCIUM CONTENT OF THE LIVER DURING HEPATIC ISCHEMIA-REPERFUSION IN DOGS

Alteration of calcium metabolism in cells has been thought to be one o f the main factors in ischemia-reperfusion injury. Serial changes in t he tissue calcium content of the liver and the correlation between cal cium level and liver injury were investigated. Experimental dogs were divided into two groups and subjected to hepatic ischemia of different duration: 60 min in Group A and 120 min in Group B, followed by reper fusion. Serum alanine aminotransferase, as an indicator of liver injur y, was more elevated in Group B than in Group A. There was no change i n hepatic calcium content during ischemia in either group. Immediately after reperfusion, there was no change in hepatic calcium level in Gr oup A, whereas in Group B it was markedly elevated. The peak value occ urred 30 min after reperfusion and gradually decreased thereafter, but did not return to pre-ischemic levels during the observation time. Pl asma calcium concentrations in hepatic venous blood were markedly decr eased in Group B 30 min and 60 min after reperfusion. These results su ggest that calcium accumulation in the liver during the early reperfus ion period may be one of the mediators of hepatic injury. To elucidate the mechanisms for elevation of calcium in hepatic tissue, serum malo ndialdehyde, a product of lipid peroxidation, was measured in hepatic venous blood. No elevation of serum malondialdehyde was observed in ei ther group, indicating that the increases in calcium may not be due to oxidative stress. Serum mitochondrial aspartate aminotransferase and electron microscopic findings were used as indicators of mitochondral injury. Serum mitochondrial aspartate aminotransferase was more elevat ed in Group B than in Group A. Mitochondrial swelling and the disappea rance of cristae were only observed in Group B. The results of this st udy seem to indicate that mitochondrial damage, as well as overall hep atocyte injury, was induced by calcium over-influx into hepatocytes du ring reperfusion after prolonged ischemia. (C) Journal of Hepatology.