Lidocaine extraction by the in vivo and isolated perfused pig liver

Berend Mets, Rosemary Hickman, Derek Chalton

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 mg · 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 μg · 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). Initial and subsequent in vivo vs ex vivo hepatic adenosine -5-triphosphate (7.1±0.6 vs 5.8±0.3 and 8.0±0.4 vs 6.6±0.3 μM · g liver-1) and energy charge (0.702±0.013 vs 0.746±0.020 and 0.744±0.017 vs 0.748±0.020) were similar, whilst total adenine nucleotides (12.9±0.9 vs 10.2±0.3 and 13.7±0.5 vs 11.5±0.8 μM · g liver-1) were less ex vivo. Hourly bile flow was similar but hepatic oxygen consumption was initially higher in vivo vs ex vivo (4.9±0.7 vs 2.6±0.3 ml O2 · 100 g-1) and subsequently similar (3.5±0.7 vs 2.5±0.2 ml O2 · 100 g-1), whilst alanine transferase and potassium concentrations were initially higher ex vivo. Perfusate composition when different from in vivo remained within the physiological range ex vivo. This study demonstrates in vivo and ex vivo hepatic lidocaine elimination to be similar in the pig, justifying the use of this isolated liver model for study of lidocaine metabolism.

Original languageEnglish (US)
Pages (from-to)1067-1074
Number of pages8
JournalJournal of Hepatology
Volume21
Issue number6
DOIs
StatePublished - Jan 1 1994

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Lidocaine
Swine
Liver
Adenine Nucleotides
Transferases
Body Temperature
Bile
Oxygen Consumption
Alanine

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Mets, Berend ; Hickman, Rosemary ; Chalton, Derek. / Lidocaine extraction by the in vivo and isolated perfused pig liver. In: Journal of Hepatology. 1994 ; Vol. 21, No. 6. pp. 1067-1074.
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abstract = "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 mg · 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 μg · 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). Initial and subsequent in vivo vs ex vivo hepatic adenosine -5-triphosphate (7.1±0.6 vs 5.8±0.3 and 8.0±0.4 vs 6.6±0.3 μM · g liver-1) and energy charge (0.702±0.013 vs 0.746±0.020 and 0.744±0.017 vs 0.748±0.020) were similar, whilst total adenine nucleotides (12.9±0.9 vs 10.2±0.3 and 13.7±0.5 vs 11.5±0.8 μM · g liver-1) were less ex vivo. Hourly bile flow was similar but hepatic oxygen consumption was initially higher in vivo vs ex vivo (4.9±0.7 vs 2.6±0.3 ml O2 · 100 g-1) and subsequently similar (3.5±0.7 vs 2.5±0.2 ml O2 · 100 g-1), whilst alanine transferase and potassium concentrations were initially higher ex vivo. Perfusate composition when different from in vivo remained within the physiological range ex vivo. This study demonstrates in vivo and ex vivo hepatic lidocaine elimination to be similar in the pig, justifying the use of this isolated liver model for study of lidocaine metabolism.",
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Lidocaine extraction by the in vivo and isolated perfused pig liver. / Mets, Berend; Hickman, Rosemary; Chalton, Derek.

In: Journal of Hepatology, Vol. 21, No. 6, 01.01.1994, p. 1067-1074.

Research output: Contribution to journalArticle

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N2 - 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 mg · 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 μg · 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). Initial and subsequent in vivo vs ex vivo hepatic adenosine -5-triphosphate (7.1±0.6 vs 5.8±0.3 and 8.0±0.4 vs 6.6±0.3 μM · g liver-1) and energy charge (0.702±0.013 vs 0.746±0.020 and 0.744±0.017 vs 0.748±0.020) were similar, whilst total adenine nucleotides (12.9±0.9 vs 10.2±0.3 and 13.7±0.5 vs 11.5±0.8 μM · g liver-1) were less ex vivo. Hourly bile flow was similar but hepatic oxygen consumption was initially higher in vivo vs ex vivo (4.9±0.7 vs 2.6±0.3 ml O2 · 100 g-1) and subsequently similar (3.5±0.7 vs 2.5±0.2 ml O2 · 100 g-1), whilst alanine transferase and potassium concentrations were initially higher ex vivo. Perfusate composition when different from in vivo remained within the physiological range ex vivo. This study demonstrates in vivo and ex vivo hepatic lidocaine elimination to be similar in the pig, justifying the use of this isolated liver model for study of lidocaine metabolism.

AB - 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 mg · 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 μg · 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). Initial and subsequent in vivo vs ex vivo hepatic adenosine -5-triphosphate (7.1±0.6 vs 5.8±0.3 and 8.0±0.4 vs 6.6±0.3 μM · g liver-1) and energy charge (0.702±0.013 vs 0.746±0.020 and 0.744±0.017 vs 0.748±0.020) were similar, whilst total adenine nucleotides (12.9±0.9 vs 10.2±0.3 and 13.7±0.5 vs 11.5±0.8 μM · g liver-1) were less ex vivo. Hourly bile flow was similar but hepatic oxygen consumption was initially higher in vivo vs ex vivo (4.9±0.7 vs 2.6±0.3 ml O2 · 100 g-1) and subsequently similar (3.5±0.7 vs 2.5±0.2 ml O2 · 100 g-1), whilst alanine transferase and potassium concentrations were initially higher ex vivo. Perfusate composition when different from in vivo remained within the physiological range ex vivo. This study demonstrates in vivo and ex vivo hepatic lidocaine elimination to be similar in the pig, justifying the use of this isolated liver model for study of lidocaine metabolism.

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