THE EFFECT OF FK506 ON WARM ISCHEMIA AND REPERFUSION INJURY IN THE RAT-LIVER

The protective effect of FK506 on hepatocytes against ischemia and rep erfusion injury was examined by evaluating the following: the high ene rgy phosphorus metabolism obtained using P-31 magnetic resonance spect roscopy (P-31-MRS) and the tissue blood flow of the liver in ischemia and the reperfusion process, mitochondrial glutamic oxaloacetic transa minase (m-GOT) and glutamic pyruvic transaminase (GPT), the survival r ates of the animals, a histological study and immunohistological stain ing for intercellular adhesion molecule-1 (ICAM-1) in the liver after ischemia. The rats were treated with FK506 1mg/kg/day i.m. for 4 days before testing. Ischemia was induced by clamping the hepatoduodenal li gament for 30 min. In P-31-MRS, the recovery of the hepatic energy sta tus after ischemia, evaluated by beta-ATP/inorganic phosphate (Pi), wa s significantly better in the FK506 group. It also coincided with the recovery of tissue blood Bow monitored with a laser Doppler flowmeter. In the histological examination, the congestion observed in the perip ortal region of the control group was mild, while there was less induc tion of ICAM-1 in the endothelial cells of the portal veins and hepati c veins in the FK506 group. From these findings, we concluded that FK5 06 had a protective effect on hepatocytes against warm ischemia and re perfusion injury, and the mechanism for this could partially be attrib uted to improved tissue blood Bow after ischemia by the modulation of immunological events.