Effect of hypoxia on the hepatic metabolism of lidocaine in the isolated perfused pig liver.
The metabolism of lidocaine to monoethylglycinexylidide has been found useful as an indicator of liver function in association with liver transplantation. It has been postulated that this is due to the common effect of hypoxic damage on liver function and lidocaine metabolism. The effects of hypoxia on the elimination of lidocaine and the formation of monoethylglycinexylidide and on indexes of liver function were investigated with the isolated perfused pig liver preparation. This study was performed at similar hepatic effluent lidocaine concentrations of approximately 5 micrograms.ml-1 in normoxic (n = 7) and hypoxic (n = 8) livers of similar mass harvested from male Landrace x Large White pigs and perfused at standard unit hepatic flow rates. Whole blood lidocaine extraction ratio was 0.63 +/- 0.02 in normoxic livers (30% O2 at oxygenator inflow). It was significantly less (0.23 +/- 0.03) in livers subjected to hypoxia (2% O2 at oxygenator inflow), as were hepatic clearance (57.1 +/- 2.1 vs. 20.3 +/- 3.1 ml.min-1.100 gm-1), intrinsic clearance (1,706 +/- 182 vs. 284 +/- 53 ml.min-1.100 gm-1) and monoethylglycinexylidide formation as indicated by monoethylglycinexylidide/lidocaine ratios in the hepatic venous effluent (0.379 +/- 0.061 vs. 0.073 +/- 0.014) (p < 0.01). Hepatic oxygen consumption, adenine nucleotide status and bile flow were significantly impaired by hypoxia. Whereas perfusate potassium concentration increased early, AST levels showed delayed increases and ALT levels showed no changes. These changes correlated strongly with hepatic lidocaine elimination (p < 0.01). We conclude that lidocaine metabolism may be an early indicator of severe hepatic hypoxia.
Mets
B
B
Department of Clinical Pharmacology, University of Cape Town Medical School, South Africa.
Hickman
R
R
Allin
R
R
Van Dyk
J
J
Lotz
Z
Z
D000704:Analysis of Variance; D000818:Animals; D004734:Energy Metabolism; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008012:Lidocaine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008657:Metabolic Clearance Rate; D010477:Perfusion / Q000379:methods; D013552:Swine; D013997:Time Factors
D008012:Lidocaine; C001173:monoethylglycinexylidide