Hepatoprotection by a PGI2 analogue in complete warm ischemia of the pig liver. Prostanoid release from the reperfused liver.
We examined the hepatoprotective effect of a prostaglandin (PG)I2 analogue by analyzing the endogenous release of prostanoid from the pig liver. Fourteen female pigs underwent 1 hr complete hepatic vascular exclusion (HVE); the portal and vena caval circulation was actively decompressed. The animals were divided into one of two groups (n = 7, each) according to pretreatment with the prostacyclin analogue (OP 2507, OP) administered via a mesenteric vein branch for 30 min at a rate of 2 micrograms/kg/min immediately prior to HVE. The plasma levels of prostaglandin E2 (PGE2), 6-keto-prostaglandin F1-alpha (6-keto-PGF1 alpha), and thromboxane B2 (TXB2), from the blood samples from the aorta, the hepatic vein, and the portal vein were serially compared for 60 min after the restoration of blood flow. Other parameters included 7-day survival rate, serum biochemistry, and endotoxin assay. A significant improvement in 7-day survival rate (6/7 vs. 1/7 for the control, P < 0.02) was observed in the OP-treated animals, associated with amelioration of serum transaminase activities but with no differences in plasma endotoxin levels. The reperfused liver progressively and substantially released PGE2 but did not generate other prostanoids (TXB2 and 6-keto-PGF1 alpha). OP pretherapy substantially suppressed hepatic generation of the PGE2 postreflow, correlating with serum transaminase levels (rs = 0.80; P < 0.01, at 60 min). We conclude that the PGI2 analogue ameliorates hepatic ischemia/reperfusion injury by down-regulating PGE2 production from the reperfused liver.
Kim
Y I
YI
Department of Surgery I, Oita Medical University, Japan.
Kai
T
T
Kitano
S
S
Ishii
T
T
Tatsuma
T
T
Kamada
N
N
Sugimachi
K
K
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003451:Cryoprotective Agents / Q000494:pharmacology*; D015232:Dinoprostone / Q000097:blood; D004731:Endotoxins / Q000097:blood; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D007511:Ischemia / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D011453:Prostaglandins / Q000097:blood / Q000378:metabolism; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood
D003451:Cryoprotective Agents; D004731:Endotoxins; D011453:Prostaglandins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C049453:OP 2507; D011464:Epoprostenol; D001219:Aspartate Aminotransferases; D015232:Dinoprostone