Evidence for cytoprotection by prostaglandin E1 with normothermic hepatic ischemia.
Although the liver is relatively resistant to normothermic ischemia, prolonged periods of inflow occlusion have produced evidence of hepatocyte injury. We have developed an animal model of liver ischemia using the pig and maintaining subtotal inflow (hepatic artery and portal vein) occlusion, allowing mesenteric portal decompression via patent portal veins through the caudate lobe, obviating the need for portosystemic shunting. This produced biochemical [aspartate transaminase (AST), lactate dehydrogenase (LDH)] and histopathologic evidence, using a microscopic grading system, of hepatocyte necrosis after 2 hr of normothermic ischemia. By administration of prostaglandin E1 (PGE1) prior to and during inflow occlusion, we have produced a statistically significant reduction in LDH (1085.9 +/- 413.5 U/liter compared to 669.1 +/- 161.4 U/liter) and AST (236.5 +/- 80.4 U/liter compared to 85.1 +/- 39.7 U/liter) (P < 0.05) between control and PGE1 animals 24 hr after reperfusion. Moreover, using the blinded microscopic grading system for hepatocellular necrosis, we have found significantly less (2.86 +/- 0.90 compared to 1.57 +/- 1.13, P < 0.01) necrosis when control and PGE1 animals were compared. Our experimental model supports the hypothesis that PGE1 exerts a cytoprotective effect during prolonged normothermic hepatic ischemia but does not aid in elucidating a mechanism for this effect.
Helling
T S
TS
Surgical Research Laboratories, University of Missouri-Kansas City School of Medicine 64111.
Hacker
K A
KA
Kragel
P J
PJ
Eisenstein
C L
CL
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D005260:Female; D007511:Ischemia / Q000201:enzymology / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008102:Liver Circulation; D009336:Necrosis; D012016:Reference Values; D013552:Swine; D013696:Temperature
D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000527:Alprostadil