Damage and repair of hepatocyte nuclear DNA after hepatic inflow occlusion

Recent reports emphasize that ischemic tissue damage is caused mainly by superoxide produced at the reperfusion rather than by ischemia itself. In this paper, the damage and repair of hepatocyte nuclear DNA of is investigated using rats with portasystemic shunt. Hepatic inflow was occluded for 30, 60 and two times 30 (with a 10-minute interval) minutes. Extent of DNA damage and repair were measured by nick-translation and 3H-thymidine incorporation, respectively. Superoxide, GOT and endotoxin were also measured. The results are as follows. 1. Sixty minutes of ischemia produced more serious DNA damage of the hepatocyte nucleus and a significant delay in repair as compared with 30 minutes of ischemia. 2. Intermittent ischemia for two times 30 minutes produced milder damage to DNA, and earlier recovery than a single ischemia of 60 minutes. 3. Serum and tissue peroxide increased after reperfusion in 60 minutes and intermittent ischemia, but not after 30 minutes of ischemia. Endotoxin level increased only in 60-minute ischemia. Histological change, neutrophilic cell infiltration, was most prominent in 60-minute ischemia. On the basis of these data, insofar as the duration of ischemia is not so long that cell damage becomes irreversible, damage by superoxide after reperfusion will be negligible. Therefore, intermittent short-term inflow occlusion is preferable in hepatic surgery.