REDUCTION OF HEPATIC REPERFUSION INJURY BY INDOMETHACIN-MEDIATED VASOCONSTRICTION - A RAT MODEL WITH TEMPORARY SPLENOCAVAL SHUNT

For reduction of radical formation during reperfusion, a lower oxygen supply by limiting the reperfusion flow rare should be beneficial for the organ. Thus, indomethacin was given prior to reperfusion for induc tion of temporary postischemic vasoconstriction. In art in vivo model (female Wistar rats, 200-250 g, n = 16) with portal decompression by a splenocaval shunt, hepatic ischemia was induced for 30 min by cross-c lamping of the hepatoduodenal ligament followed by portal intravenous injection of indomethacin (2 mg/kg body wt) at the end of ischemia. Li ver injury was assessed by serum levels of Aspartat-aminotransferase ( ASAT) and Alanin-aminotransferase (ALAT) that were determined prior to ischemia, on days 2, 4, 6 and 21 postoperatively. The local tissue pO (2) was measured preischemically, 1 h after reperfusion and on day 21. Application of indomethacin significantly reduced the local tissue- p O(2) by about 50% after 1 h of reperfusion (p < .05). The increase in serum ASAT levels on day 2 was significantly diminished after indometh acin application (p < .05). ALAT values on day 2 showed a significant increase in the central group but did not differ from baseline in the indomethacin group. These data support the hypothesis that temporarily limited reperfusion results in an amelioration of reperfusion injury, although further studies with more selectively vasoactive agents must still be performed since indomethacin also has a major effect on the eicosanoid metabolism eicosanoid metabolism.