Recovery of hepatic drug extraction after hypothermic preservation

S. D. Kelley, C. B. Cauldwell, D. M. Fisher, M. Lau, M. L. Sharma, R. A. Weisiger

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: To determine whether liver preservation before transplantation impairs hepatic drug metabolism, hepatic extraction of drugs with different metabolic pathways (fentanyl, morphine, and vecuronium) in isolated rat livers was measured either immediately or after 24 h of hypothermia at 4°C using a standard preservation-reperfusion sequence. Methods: Isolated rat livers were perfused via the portal vein for 30 min to document initial viability. Test livers (n = 5) were perfused with iced Belzer solution, stored for 24 h at 4°C, and flushed with 6% hetastarch. After hypothermic preservation for 24 h, or in control livers (n = 5) immediately after the 30- min perfusion, livers were perfused single-pass at a constant flow rate with solutions containing fentanyl, morphine, and vecuronium at 37°C. Perfusate and bile samples were obtained at regular intervals for 64 min, after which liver tissue was harvested for analysis. Drug concentrations were measured using radioimmunoassay and gas chromatography. Metabolic capacity of the liver was estimated from the extraction fraction of each drug at steady- state. Results: After warming to 37°C, preserved livers consumed oxygen and produced bile at rates similar to that of control livers. Hypothermic preservation did not affect extraction of fentanyl and morphine. Vecuronium extraction was initially less in preserved livers, but this difference disappeared as the preserved livers returned to 37°C (<16 min). Biliary excretion and tissue concentrations of vecuronium were similar in each group. Conclusions: Hypothermic preservation does not significantly impair extraction of these drugs in this liver preservation model. If these results apply to human liver transplantation, little danger of drug accumulation exists during the early postoperative period if hepatic function is normal.

Original languageEnglish (US)
Pages (from-to)251-258
Number of pages8
JournalAnesthesiology
Volume82
Issue number1
DOIs
StatePublished - 1995

Fingerprint

Liver
Pharmaceutical Preparations
Vecuronium Bromide
Fentanyl
Morphine
Bile
Liver Transplantation
Hydroxyethyl Starch Derivatives
Portal Vein
Metabolic Networks and Pathways
Hypothermia
Postoperative Period
Gas Chromatography
Reperfusion
Radioimmunoassay
Perfusion
Oxygen

Keywords

  • Anesthetics, intravenous: fentanyl; morphine
  • Drug metabolism: hepatic
  • Neuromuscular relaxants: vecuronium
  • Transplantation, liver: preservation

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Kelley, S. D., Cauldwell, C. B., Fisher, D. M., Lau, M., Sharma, M. L., & Weisiger, R. A. (1995). Recovery of hepatic drug extraction after hypothermic preservation. Anesthesiology, 82(1), 251-258. https://doi.org/10.1097/00000542-199501000-00030

Recovery of hepatic drug extraction after hypothermic preservation. / Kelley, S. D.; Cauldwell, C. B.; Fisher, D. M.; Lau, M.; Sharma, M. L.; Weisiger, R. A.

In: Anesthesiology, Vol. 82, No. 1, 1995, p. 251-258.

Research output: Contribution to journalArticle

Kelley, SD, Cauldwell, CB, Fisher, DM, Lau, M, Sharma, ML & Weisiger, RA 1995, 'Recovery of hepatic drug extraction after hypothermic preservation', Anesthesiology, vol. 82, no. 1, pp. 251-258. https://doi.org/10.1097/00000542-199501000-00030
Kelley SD, Cauldwell CB, Fisher DM, Lau M, Sharma ML, Weisiger RA. Recovery of hepatic drug extraction after hypothermic preservation. Anesthesiology. 1995;82(1):251-258. https://doi.org/10.1097/00000542-199501000-00030
Kelley, S. D. ; Cauldwell, C. B. ; Fisher, D. M. ; Lau, M. ; Sharma, M. L. ; Weisiger, R. A. / Recovery of hepatic drug extraction after hypothermic preservation. In: Anesthesiology. 1995 ; Vol. 82, No. 1. pp. 251-258.
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abstract = "Background: To determine whether liver preservation before transplantation impairs hepatic drug metabolism, hepatic extraction of drugs with different metabolic pathways (fentanyl, morphine, and vecuronium) in isolated rat livers was measured either immediately or after 24 h of hypothermia at 4°C using a standard preservation-reperfusion sequence. Methods: Isolated rat livers were perfused via the portal vein for 30 min to document initial viability. Test livers (n = 5) were perfused with iced Belzer solution, stored for 24 h at 4°C, and flushed with 6{\%} hetastarch. After hypothermic preservation for 24 h, or in control livers (n = 5) immediately after the 30- min perfusion, livers were perfused single-pass at a constant flow rate with solutions containing fentanyl, morphine, and vecuronium at 37°C. Perfusate and bile samples were obtained at regular intervals for 64 min, after which liver tissue was harvested for analysis. Drug concentrations were measured using radioimmunoassay and gas chromatography. Metabolic capacity of the liver was estimated from the extraction fraction of each drug at steady- state. Results: After warming to 37°C, preserved livers consumed oxygen and produced bile at rates similar to that of control livers. Hypothermic preservation did not affect extraction of fentanyl and morphine. Vecuronium extraction was initially less in preserved livers, but this difference disappeared as the preserved livers returned to 37°C (<16 min). Biliary excretion and tissue concentrations of vecuronium were similar in each group. Conclusions: Hypothermic preservation does not significantly impair extraction of these drugs in this liver preservation model. If these results apply to human liver transplantation, little danger of drug accumulation exists during the early postoperative period if hepatic function is normal.",
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AU - Sharma, M. L.

AU - Weisiger, R. A.

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AB - Background: To determine whether liver preservation before transplantation impairs hepatic drug metabolism, hepatic extraction of drugs with different metabolic pathways (fentanyl, morphine, and vecuronium) in isolated rat livers was measured either immediately or after 24 h of hypothermia at 4°C using a standard preservation-reperfusion sequence. Methods: Isolated rat livers were perfused via the portal vein for 30 min to document initial viability. Test livers (n = 5) were perfused with iced Belzer solution, stored for 24 h at 4°C, and flushed with 6% hetastarch. After hypothermic preservation for 24 h, or in control livers (n = 5) immediately after the 30- min perfusion, livers were perfused single-pass at a constant flow rate with solutions containing fentanyl, morphine, and vecuronium at 37°C. Perfusate and bile samples were obtained at regular intervals for 64 min, after which liver tissue was harvested for analysis. Drug concentrations were measured using radioimmunoassay and gas chromatography. Metabolic capacity of the liver was estimated from the extraction fraction of each drug at steady- state. Results: After warming to 37°C, preserved livers consumed oxygen and produced bile at rates similar to that of control livers. Hypothermic preservation did not affect extraction of fentanyl and morphine. Vecuronium extraction was initially less in preserved livers, but this difference disappeared as the preserved livers returned to 37°C (<16 min). Biliary excretion and tissue concentrations of vecuronium were similar in each group. Conclusions: Hypothermic preservation does not significantly impair extraction of these drugs in this liver preservation model. If these results apply to human liver transplantation, little danger of drug accumulation exists during the early postoperative period if hepatic function is normal.

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KW - Neuromuscular relaxants: vecuronium

KW - Transplantation, liver: preservation

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