Platelet-activating factor in hepatic ischemia/reperfusion injury. The effects of a PAF antagonist combined with a prostaglandin I2 analogue.
The effects of TCV-309, a specific platelet-activating factor (PAF) antagonist, and OP-41483, a prostaglandin I2 analogue, on warm ischemia/reperfusion injury of the rat liver were studied. Rats were divided into five groups by the duration of warm ischemia and the treatment used. The NS1 group (normal saline pretreatment) had 60 min of warm ischemia, while the NS2 group (normal saline pretreatment), the PGI2 group (OP-41483, 500 ng/kg/min pretreatment), the TCV group (TCV-309, 3 micrograms/kg), and the PGI2+TCV group (both the above dosages) underwent 120 min of warm ischemia. Postoperative survival after 30 days, bile secretion, serum endotoxin levels, and tissue glutathione levels after 60 min of reperfusion were compared between the groups. The survival rates for the NS1, NS2, PGI2, TCV, and PGI2+TCV groups were 80%, 0%, 50%, 80%, and 86.7%, respectively. Bile secretion, which has a strong correlationship with hepatic cellular ATP level, was strongly correlated with survival. The NS2 group had a high serum endotoxin level--however, the PGI2 and PGI2+TCV groups had normal levels. Although there were some discrepancies between survival and the tissue glutathione level, combined treatment with the PGI2 analogue and TCV-309 was most effective in inhibited oxidative stress. In conclusion, TCV-309 increased the survival rate after 120 min of warm hepatic ischemia without endotoxemia by the PGI2 analogue. This finding suggest that warm ischemia/reperfusion injury is related to the generation of PAF. Combined pretreatment with TCV-309 and a PGI2 analogue may be useful in liver transplantation.
Second Department of Surgery, Hamamatsu University School of Medicine, Japan.
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Nishiyama
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Nakamura
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Suzuki
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Baba
D000818:Animals; D001646:Bile / Q000378:metabolism; D004731:Endotoxins / Q000097:blood; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D007511:Ischemia / Q000503:physiopathology; D007546:Isoquinolines / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008297:Male; D010972:Platelet Activating Factor / Q000502:physiology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D044005:Tetrahydroisoquinolines
D004731:Endotoxins; D007546:Isoquinolines; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; D044005:Tetrahydroisoquinolines; D011464:Epoprostenol; D005978:Glutathione; C035847:ataprost; C067430:TCV 309