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Cerebral uptake of morphine in the pig calculated from arterio-venous plasma concentration gradients: an alternative to tissue microdialysis

Björkman, Sven; Åkeson, Jonas LU ; Helfer, Mats; Fyge, Åsa and Gustafsson, Lars L (1995) In Life Sciences 57(25). p.2335-2345
Abstract
The aim of this study was to characterize the reversible cerebral uptake of morphine in the pig by measuring the changing arterio-venous plasma concentration gradient over the brain. Seven pigs were anaesthetized by continuous infusions of ketamine and pancuronium and ventilated with oxygen in nitrous oxide. During and after 5-min intravenous infusions of morphine hydrochloride, blood samples were drawn from a central artery and from the internal jugular vein. Concomitantly, cerebral blood flow (CBF) was repeatedly measured as clearance of 133Xe from the brain after intracarotid injection. Plasma concentrations of morphine and, in samples from two animals, morphine glucuronides were assayed by high-performance liquid chromatography. Drug... (More)
The aim of this study was to characterize the reversible cerebral uptake of morphine in the pig by measuring the changing arterio-venous plasma concentration gradient over the brain. Seven pigs were anaesthetized by continuous infusions of ketamine and pancuronium and ventilated with oxygen in nitrous oxide. During and after 5-min intravenous infusions of morphine hydrochloride, blood samples were drawn from a central artery and from the internal jugular vein. Concomitantly, cerebral blood flow (CBF) was repeatedly measured as clearance of 133Xe from the brain after intracarotid injection. Plasma concentrations of morphine and, in samples from two animals, morphine glucuronides were assayed by high-performance liquid chromatography. Drug flux (Jnet) from arterial blood to brain was calculated from the arterio-venous plasma concentration gradients, the blood:plasma concentration ratio and CBF. Uptake of morphine from arterial blood to brain was very rapid, with a maximal Jnet typically at 3 min after the beginning of the infusion. The initial cerebral extraction of morphine was close to 50%. When the arterial and jugular venous concentration curves crossed, 1-5 min after the end of the infusion, the initially rapid uptake of morphine changed into a slow and steady release. The cerebral extraction of morphine glucuronides was comparable to that of morphine, however, Jnet was lower due to lower plasma concentrations at time of maximal extraction. The findings demonstrate how the cerebral uptake and release of morphine and its metabolites can be studied with a method that is entirely non-invasive to the brain and permits very flexible sampling. Uptake and release of drug is observed directly and need not be inferred from cerebral concentration curves. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
morphine glucuronides, morphine, arterio-venous concentration gradients, cerebral uptake, cerebral extraction
in
Life Sciences
volume
57
issue
25
pages
2335 - 2345
publisher
Elsevier
external identifiers
  • pmid:7491092
  • scopus:0028828349
ISSN
1879-0631
DOI
10.1016/0024-3205(95)02228-B
language
English
LU publication?
yes
id
1a964115-3a9d-416a-b5b9-dbca5426a122 (old id 1109382)
date added to LUP
2008-07-28 13:51:53
date last changed
2017-01-01 04:23:09
@article{1a964115-3a9d-416a-b5b9-dbca5426a122,
  abstract     = {The aim of this study was to characterize the reversible cerebral uptake of morphine in the pig by measuring the changing arterio-venous plasma concentration gradient over the brain. Seven pigs were anaesthetized by continuous infusions of ketamine and pancuronium and ventilated with oxygen in nitrous oxide. During and after 5-min intravenous infusions of morphine hydrochloride, blood samples were drawn from a central artery and from the internal jugular vein. Concomitantly, cerebral blood flow (CBF) was repeatedly measured as clearance of 133Xe from the brain after intracarotid injection. Plasma concentrations of morphine and, in samples from two animals, morphine glucuronides were assayed by high-performance liquid chromatography. Drug flux (Jnet) from arterial blood to brain was calculated from the arterio-venous plasma concentration gradients, the blood:plasma concentration ratio and CBF. Uptake of morphine from arterial blood to brain was very rapid, with a maximal Jnet typically at 3 min after the beginning of the infusion. The initial cerebral extraction of morphine was close to 50%. When the arterial and jugular venous concentration curves crossed, 1-5 min after the end of the infusion, the initially rapid uptake of morphine changed into a slow and steady release. The cerebral extraction of morphine glucuronides was comparable to that of morphine, however, Jnet was lower due to lower plasma concentrations at time of maximal extraction. The findings demonstrate how the cerebral uptake and release of morphine and its metabolites can be studied with a method that is entirely non-invasive to the brain and permits very flexible sampling. Uptake and release of drug is observed directly and need not be inferred from cerebral concentration curves.},
  author       = {Björkman, Sven and Åkeson, Jonas and Helfer, Mats and Fyge, Åsa and Gustafsson, Lars L},
  issn         = {1879-0631},
  keyword      = {morphine glucuronides,morphine,arterio-venous concentration gradients,cerebral uptake,cerebral extraction},
  language     = {eng},
  number       = {25},
  pages        = {2335--2345},
  publisher    = {Elsevier},
  series       = {Life Sciences},
  title        = {Cerebral uptake of morphine in the pig calculated from arterio-venous plasma concentration gradients: an alternative to tissue microdialysis},
  url          = {http://dx.doi.org/10.1016/0024-3205(95)02228-B},
  volume       = {57},
  year         = {1995},
}