Effects of prostaglandin I2, superoxide dismutase, and catalase on ischemia-reperfusion injury in liver transplantation.
This study evaluated the effects of a prostaglandin I2 analogue (aPGI2), superoxide dismutase (SOD), and catalase (CAT) on hepatic injury after warm ischemia and reperfusion in terms of survival, mitochondrial function, serum enzymes, and histology. Hepatic ischemia was created in rats by clamping the hepatoduodenal ligament for 90 min with splenofemoral bypass. Reperfusion was induced by unclamping the vessels and disconnecting the splenofemoral bypass. Then aPGI2 (350 ng/kg/min) was infused for 60 min just before hepatic ischemia, and SOD and CAT (5,000 units/kg each) were administered immediately before the start of reperfusion. Serum enzyme and mitochondrial function assessments of livers were made just after ischemia, and after 2 hr of reperfusion. Survival rate was also assessed in a separate group of rats. Liver enzymes such as SGOT, SGPT, and LDH showed no correlation to liver viability. The administration of aPGI2 alone showed no effect on ischemically injured mitochondria; however, the free radical scavengers (SOD, CAT), in combination with aPGI2, showed significant improvement of mitochondrial function together with extension of survival. The ultrastructure of hepatocytes was better preserved in the treated groups. These agents improved the viability of ischemic-reperfused injured livers.
Tanaka
J
J
Department of Artificial Organs, Cleveland Clinic Foundation, Ohio 44195-5132.
Malchesky
P S
PS
Omokawa
S
S
Goldcamp
J B
JB
Harasaki
H
H
Vogt
D P
DP
Broughan
T A
TA
Nosé
Y
Y
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002374:Catalase / Q000494:pharmacology*; D011464:Epoprostenol / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000494:pharmacology*
D011464:Epoprostenol; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase