Lidocaine-metabolizing activity after warm ischemia and reperfusion of the rat liver in vivo.
The effect of warm ischemia on lidocaine-metabolizing activity was examined in vivo. Total liver ischemia was produced for 1 hr in Sprague-Dawley rats by clamping the portal vein and hepatic artery at the hilum. Livers were then reperfused, and liver microsomes were prepared before and 0, 2, 6, and 24 hr, and 3, 6, and 10 days after reperfusion. Microsomal lidocaine-metabolizing activity and cytochrome P-450 content were examined. Lidocaine N-deethylase activity was decreased from 2.25 +/- 0.33 to 0.97 +/- 0.21 nmol/mg protein/min (mean +/- SD) 24 hr after reperfusion. This inhibition was prolonged, and activity gradually recovered after 10 days. The cytochrome P-450 content showed the same tendency. On the other hand, serum levels of alanine aminotransferase increased significantly 2 hr after reperfusion and returned to control levels 3 days after reperfusion. Liver blood flow recovered rapidly after unclamping and reached baseline levels within 6 hr. Our results suggest that after warm ischemia, prolonged hepatic dysfunction in drug metabolism, which cannot be detected by evaluating serum enzymes or liver blood flow, exists at the microsomal level.
Izuishi
K
K
Department of Surgery, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
Wakabayashi
H
H
Maeba
T
T
Ryu
M
M
Maeta
H
H
D000410:Alanine Transaminase / Q000097:blood; D000779:Anesthetics, Local / Q000493:pharmacokinetics*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008012:Lidocaine / Q000493:pharmacokinetics*; D008099:Liver / Q000098:blood supply* / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology*; D017694:Rewarming; D013997:Time Factors
D000779:Anesthetics, Local; D003577:Cytochrome P-450 Enzyme System; D008012:Lidocaine; D010088:Oxidoreductases; C108759:lidocaine N-deethylase; D000410:Alanine Transaminase