Lidocaine extraction by the in vivo and isolated perfused pig liver.
Hepatic lidocaine elimination is increasingly being used to assess hepatic function. Although the isolated liver is extensively used as a model of in vivo function, it is necessary to determine whether this is a suitable model for in vivo lidocaine elimination. Fourteen male pigs (22-25 kg) were divided into two groups. Seven were anesthetized, and catheters and perivascular flow probes placed for transhepatic sampling and hepatic arterial and portal venous flow measurement. Sampling was performed at hourly intervals to determine hepatic function and plasma composition. Hepatic lidocaine elimination was determined during the second hour of a lidocaine infusion (1.41 mg.kg-1.min-1 for 10 min, then 0.165 m.kg-1.min-1), during which time the mean hepatic blood flow rates, plasma acid base status and body temperature were measured so that these could be emulated in the isolated perfused liver experiments. Seven male pigs were then anesthetized and the liver resected and cannulated for isolated liver perfusion. Hepatic arterial and portal venous blood flow and perfusate temperature were set to the mean in vivo values, and hepatic function and perfusate composition assessed at corresponding times. Hepatic lidocaine elimination was determined at a similar hepatic inflow whole blood concentration (+/- 5 micrograms.ml-1) to that in vivo over the second hour of lidocaine administration (40 mg bolus, then 2.8 mg.min-1). Lidocaine extraction ratio in vivo (0.61 +/- 0.04) [mean +/- SEM] and ex vivo (0.63 +/- 0.02) was similar, as was hepatic blood clearance (381 +/- 70 vs 363 +/- 16 ml.min-1) and hepatic blood intrinsic clearance (1132 +/- 280 vs 1069 +/- 109 ml.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Mets
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B
Department of Clinical Pharmacology, University of Cape Town Medical School, South Africa.
Hickman
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R
Chalton
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D
D000227:Adenine Nucleotides / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001769:Blood / Q000378:metabolism; D066298:In Vitro Techniques; D008012:Lidocaine / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation; D008297:Male; D010101:Oxygen Consumption; D010477:Perfusion; D013552:Swine
D000227:Adenine Nucleotides; D008012:Lidocaine; D000410:Alanine Transaminase