Protective effect of platelet-activating factor antagonist on hepatic energy metabolism following transient hepatic inflow occlusion in rabbits.
To investigate whether or not platelet-activating factor (PAF) is a mediator of the liver injury resulting from transient hepatic inflow occlusion (Pringle's maneuver), the effect of pretreatment with a potent PAF antagonist (CV6209) on hepatic energy metabolism was evaluated following 30 min of inflow occlusion in rabbits. At 60 min after declamping, the arterial ketone body ratio (AKBR; acetoacetate/3-hydroxybutyrate), reflecting hepatic mitochondrial redox state (NAD+/NADH), increased to 1.10 +/- 0.05 (mean +/- SEM) in the CV6209 (5 mg/kg)-pretreated group (group 1, n = 5) compared with 0.72 +/- 0.06 (P less than 0.01) in the untreated group (group 2, n = 5). Hepatic energy charge at 60 min after declamping was significantly higher in group 1 than in group 2 (0.871 +/- 0.010 vs. 0.800 +/- 0.023; P less than 0.05). Pretreatment with CV6209 had no significant influence on these parameters in sham-operated animals. The present study demonstrates that pretreatment with CV6209 has a protective effect against the impairment of hepatic energy metabolism following transient hepatic inflow occlusion.
Takada
Y
Y
Second Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Shimahara
Y
Y
Yamaguchi
T
T
Nishizawa
F
F
Mori
K
K
Yamaoka
Y
Y
Ozawa
K
K
D000818:Animals; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects; D007511:Ischemia / Q000188:drug therapy*; D007657:Ketone Bodies / Q000032:analysis; D007773:Lactates / Q000097:blood; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011168:Portal System; D011726:Pyridinium Compounds / Q000494:pharmacology*; D011817:Rabbits
D007657:Ketone Bodies; D007773:Lactates; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C053321:CV 6209