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 rate should be beneficial for the organ. Thus, indomethacin was given prior to reperfusion for induction of temporary postischemic vasoconstriction. In an 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-clamping of the hepatoduodenal ligament followed by portal intravenous injection of indomethacin (2 mg/kg body wt) at the end of ischemia. Liver injury was assessed by serum levels of Aspartat-aminotransferase (ASAT) and Alaninaminotransferase (ALAT) that were determined prior to ischemia, on days 2, 4, 6 and 21 postoperatively. The local tissue pO2 was measured preischemically, 1 h after reperfusion and on day 21. Application of indomethacin significantly reduced the local tissue-pO2 by about 50% after 1 h of reperfusion (p < .05). The increase in serum ASAT levels on day 2 was significantly diminished after indomethacin application (p < .05). ALAT values on day 2 showed a significant increase in the control 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.
Spiegel
H U
HU
Department of General Surgery-Surgical Research Westfaelische Wilhelms-University Muenster, Germany.
Bremer
C
C
Boin
C
C
Langer
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D007213:Indomethacin / Q000627:therapeutic use*; D008099:Liver / Q000098:blood supply* / Q000503:physiopathology; D011170:Portasystemic Shunt, Surgical; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy*; D013162:Splenic Vein / Q000601:surgery; D014662:Vasoconstrictor Agents / Q000627:therapeutic use; D014682:Vena Cava, Inferior / Q000601:surgery
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014662:Vasoconstrictor Agents; D007213:Indomethacin