The effects of PGI2 analog (OP-41483) on perfused porcine liver.
The effects of a prostacyclin analog OP-41483 on energy metabolism were studied in an isolated porcine liver perfused with human blood for 8 h. OP-41483 was administered intravenously at a rate of 0.3 microgram/kg/min during the procurement and into the perfusate at a rate of 1.0 microgram/min during perfusion. Acetoacetate, beta-hydroxybutyrate, lactate, and pyruvate were measured before perfusion and at 1, 2, 3, 5, and 8 h after perfusion, from which values the ketone body ration (acetoacetate/beta-hydroxybutyrate, KBR), reflecting the redox state of liver mitochondria, was calculated. In the OP-41483 group, KBR increased rapidly from 0.34 to 0.95, 1.61, 1.51, 2.35, and 2.04, and lactate decreased rapidly from 9.81 to 6.30, 4.51, 3.22, 2.39, and 1.33 mmol/L at the respective hours after perfusion. There were significant differences after 3 h of perfusion as compared with the control group (p less than 0.05). These results suggest that administration of OP-41483 causes an increase in mitochondrial NAD+/NADH ratio (oxidized and reduced forms of free nicotinamide-adenine dinucleotides), leading to an enhancement of the metabolic capacity of the perfused liver.
Kimoto
M
M
Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Shimahara
Y
Y
Ikai
I
I
Wakashiro
S
S
Ozaki
N
N
Tatsumi
Y
Y
Tanaka
A
A
Kamiyama
Y
Y
Yamaoka
Y
Y
Ozawa
K
K
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects*; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D005260:Female; D006885:Hydroxybutyrates / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D010477:Perfusion; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D011773:Pyruvates / Q000378:metabolism; D013552:Swine
D000090:Acetoacetates; D006885:Hydroxybutyrates; D007657:Ketone Bodies; D007773:Lactates; D011465:Prostaglandins, Synthetic; D011773:Pyruvates; D011464:Epoprostenol; C035847:ataprost; D020155:3-Hydroxybutyric Acid