Involvement of platelet activating factor in microcirculatory disturbances after global hepatic ischemia.
This study aimed at analyzing the involvement of platelet activating factor (PAF) in ischemia/reperfusion injury (I/R) of the liver. Male Wistar rats under pentobarbital anesthesia were subjected to 60 min of normothermic ischemia of the left and median liver lobes, followed by 30 min of reperfusion in vivo. Blood pressure and body temperature were controlled throughout the experiment. Preischemic injection of a specific PAF antagonist (BN52021, 5 mg/kg body mass) resulted in significant reduction of postischemic enzyme loss into the serum from the vascular endothelium (purine nucleoside phosphorylase: 56.9 +/- 11.4 vs 86.6 +/- 20.4 U/l**) and the hepatic parenchyme (alanine aminotransferase: 176 +/- 60 vs 519 +/- 180 U/l***), accompanied by a significant increase of hepatic bile production (1.28 +/- .32 vs 0.80 +/- 0.16 microliter/g/min*) and tissue levels of ATP (6.12 +/- 1.73 vs 4.21 +/- 1.30 mumol/g*). Laser Doppler flowmetry revealed a significant improvement by BN52021 of left lobular erythrocyte flux recovery from 27 +/- 25 to 78 +/- 19% of respective preischemic control values. The data give evidence for an implication of PAF in I/R damage to the vascular endothelium and in impaired parenchymal function of the liver, probably due to altered microvascular reperfusion. Treatment with PAF antagonists should improve results after liver surgery under ischemic conditions. (*;**;***: P < 0.05; 0.01; 0.001).
Minor
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Institute for Experimental Medicine, University of Cologne, Germany.
Isselhard
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W
Yamaguchi
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000187:drug effects; D004224:Diterpenes; D046934:Ginkgolides; D007511:Ischemia / Q000150:complications* / Q000503:physiopathology*; D007783:Lactones / Q000494:pharmacology; D008102:Liver Circulation; D008297:Male; D008833:Microcirculation; D009994:Osmolar Concentration; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D000255:Adenosine Triphosphate; C045856:ginkgolide B