EFFECT OF HYPOXIA ON THE HEPATIC-METABOLISM OF LIDOCAINE IN THE ISOLATED PERFUSED PIG-LIVER

The metabolism of lidocaine to monoethylglycine-xylidide has been foun d useful as an indicator of liver function in association with liver t ransplantation. It has been postulated that this is due to the common effect of hypoxic damage on liver function and lidocaine metabolism. T he effects of hypoxia on the elimination of lidocaine and the formatio n of monoethylglycinexylidide and on indexes of liver function were in vestigated with the isolated perfused pig liver preparation. This stud y was performed at similar hepatic effluent lidocaine concentrations o f approximately 5 mug . ml-1 in normoxic (n = 7) and hypoxic (n = 8) l ivers of similar mass harvested from male Landrace x Large White pigs and perfused at standard unit hepatic flow rates. Whole blood lidocain e extraction ratio was 0.63 +/- 0.02 in normoxic livers (30% 0, at oxy genator inflow). It was significantly less (0.23 +/- 0.03) in livers s ubjected to hypoxia (2% O2 at oxygenator inflow), as were hepatic clea rance (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 mo noethylglycinexylidide formation as indicated by monoethylglycinexylid ide/ lidocaine ratios in the hepatic venous effluent (0.379 +/- 0.061 vs. 0.073 +/- 0.014) (p < 0.01). Hepatic oxygen consumption, adenine n ucleotide 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 chan ges correlated strongly with hepatic lidocaine elimination (p < 0.01). We conclude that lidocaine metabolism may be an early indicator of se vere hepatic hypoxia.