Hexafluorobenzene acts in the spinal cord, whereas o-difluorobenzene acts in both brain and spinal cord, to produce immobility

Joseph F. Antognini, Douglas E. Raines, Ken Solt, Linda S Barter, Richard J. Atherley, Emigdio Bravo, Michael J. Laster, Katarzyna Jankowska, Edmond I. Eger

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

BACKGROUND: Previous work demonstrated that isoflurane and halothane act on the spinal cord rather than on the brain to produce immobility in the face of noxious stimulation. These anesthetics share many effects on specific receptors, and thus do not test the broad applicability of the mediation of immobility by the cord. We sought to test such an applicability by determining whether the cord mediated the immobilizing effects of two aromatic anesthetics that differ greatly in their ability to block N-methyl-d-aspartate receptors. METHODS: We investigated the actions of hexafluorobenzene (HFB) and o-difluorobenzene (ODFB) using an intact goat model that allowed selective delivery of anesthetics to the brain. Because our results suggested a significant cerebral effect of ODFB, in other goats we administered halothane 0.5% to the brain, while determining the ODFB concentration delivered to the body (the cord) required for immobility. We chose halothane because the present and previous studies found that cerebral halothane concentrations alone required for producing immobility far exceeded those required in the cord. We also applied the above techniques to another benzene-containing anesthetic, propofol. RESULTS: Prebypass minimum alveolar concentration (MAC) for HFB was 0.82% ± 0.14% (mean ± sd); increased to 2.04% ± 0.8% (P < 0.01) during selective delivery to the cranial circulation; and returned to 0.79% ± 0.28% postbypass. Corresponding values for ODFB were 0.46% ± 0.07%, 0.63% ± 0.12% (P < 0.05), and 0.44% ± 0.10%. ODFB MAC was 0.32% ± 0.17% during selective halothane delivery to brain. But when ODFB was administered to the whole body, MAC was 0.37% ± 0.05%, (NS). Like HFB, the halothane requirement increased threefold when delivered only to the head. In four of five animals, propofol requirements increased by 240%, but in one animal propofol requirements decreased, and the overall change was not statistically significant. CONCLUSIONS: These data suggest that HFB, like halothane, produces immobility, predominantly by a spinal cord action, and that HFB differs from ODFB with respect to brain versus spinal sites of action. Nonetheless, although ODFB can produce immobility via a cerebral action, it also can do this via an independent action in the spinal cord. Thus, our results continue to support the spinal cord as the primary site at which inhaled anesthetics, and perhaps propofol, produce immobility.

Original languageEnglish (US)
Pages (from-to)822-828
Number of pages7
JournalAnesthesia and Analgesia
Volume104
Issue number4
DOIs
StatePublished - Apr 2007

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Halothane
Spinal Cord
Anesthetics
Brain
Propofol
Goats
hexafluorobenzene
1,2-difluorobenzene
Isoflurane
Benzene
Head

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Hexafluorobenzene acts in the spinal cord, whereas o-difluorobenzene acts in both brain and spinal cord, to produce immobility. / Antognini, Joseph F.; Raines, Douglas E.; Solt, Ken; Barter, Linda S; Atherley, Richard J.; Bravo, Emigdio; Laster, Michael J.; Jankowska, Katarzyna; Eger, Edmond I.

In: Anesthesia and Analgesia, Vol. 104, No. 4, 04.2007, p. 822-828.

Research output: Contribution to journalArticle

Antognini, Joseph F. ; Raines, Douglas E. ; Solt, Ken ; Barter, Linda S ; Atherley, Richard J. ; Bravo, Emigdio ; Laster, Michael J. ; Jankowska, Katarzyna ; Eger, Edmond I. / Hexafluorobenzene acts in the spinal cord, whereas o-difluorobenzene acts in both brain and spinal cord, to produce immobility. In: Anesthesia and Analgesia. 2007 ; Vol. 104, No. 4. pp. 822-828.
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title = "Hexafluorobenzene acts in the spinal cord, whereas o-difluorobenzene acts in both brain and spinal cord, to produce immobility",
abstract = "BACKGROUND: Previous work demonstrated that isoflurane and halothane act on the spinal cord rather than on the brain to produce immobility in the face of noxious stimulation. These anesthetics share many effects on specific receptors, and thus do not test the broad applicability of the mediation of immobility by the cord. We sought to test such an applicability by determining whether the cord mediated the immobilizing effects of two aromatic anesthetics that differ greatly in their ability to block N-methyl-d-aspartate receptors. METHODS: We investigated the actions of hexafluorobenzene (HFB) and o-difluorobenzene (ODFB) using an intact goat model that allowed selective delivery of anesthetics to the brain. Because our results suggested a significant cerebral effect of ODFB, in other goats we administered halothane 0.5{\%} to the brain, while determining the ODFB concentration delivered to the body (the cord) required for immobility. We chose halothane because the present and previous studies found that cerebral halothane concentrations alone required for producing immobility far exceeded those required in the cord. We also applied the above techniques to another benzene-containing anesthetic, propofol. RESULTS: Prebypass minimum alveolar concentration (MAC) for HFB was 0.82{\%} ± 0.14{\%} (mean ± sd); increased to 2.04{\%} ± 0.8{\%} (P < 0.01) during selective delivery to the cranial circulation; and returned to 0.79{\%} ± 0.28{\%} postbypass. Corresponding values for ODFB were 0.46{\%} ± 0.07{\%}, 0.63{\%} ± 0.12{\%} (P < 0.05), and 0.44{\%} ± 0.10{\%}. ODFB MAC was 0.32{\%} ± 0.17{\%} during selective halothane delivery to brain. But when ODFB was administered to the whole body, MAC was 0.37{\%} ± 0.05{\%}, (NS). Like HFB, the halothane requirement increased threefold when delivered only to the head. In four of five animals, propofol requirements increased by 240{\%}, but in one animal propofol requirements decreased, and the overall change was not statistically significant. CONCLUSIONS: These data suggest that HFB, like halothane, produces immobility, predominantly by a spinal cord action, and that HFB differs from ODFB with respect to brain versus spinal sites of action. Nonetheless, although ODFB can produce immobility via a cerebral action, it also can do this via an independent action in the spinal cord. Thus, our results continue to support the spinal cord as the primary site at which inhaled anesthetics, and perhaps propofol, produce immobility.",
author = "Antognini, {Joseph F.} and Raines, {Douglas E.} and Ken Solt and Barter, {Linda S} and Atherley, {Richard J.} and Emigdio Bravo and Laster, {Michael J.} and Katarzyna Jankowska and Eger, {Edmond I.}",
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T1 - Hexafluorobenzene acts in the spinal cord, whereas o-difluorobenzene acts in both brain and spinal cord, to produce immobility

AU - Antognini, Joseph F.

AU - Raines, Douglas E.

AU - Solt, Ken

AU - Barter, Linda S

AU - Atherley, Richard J.

AU - Bravo, Emigdio

AU - Laster, Michael J.

AU - Jankowska, Katarzyna

AU - Eger, Edmond I.

PY - 2007/4

Y1 - 2007/4

N2 - BACKGROUND: Previous work demonstrated that isoflurane and halothane act on the spinal cord rather than on the brain to produce immobility in the face of noxious stimulation. These anesthetics share many effects on specific receptors, and thus do not test the broad applicability of the mediation of immobility by the cord. We sought to test such an applicability by determining whether the cord mediated the immobilizing effects of two aromatic anesthetics that differ greatly in their ability to block N-methyl-d-aspartate receptors. METHODS: We investigated the actions of hexafluorobenzene (HFB) and o-difluorobenzene (ODFB) using an intact goat model that allowed selective delivery of anesthetics to the brain. Because our results suggested a significant cerebral effect of ODFB, in other goats we administered halothane 0.5% to the brain, while determining the ODFB concentration delivered to the body (the cord) required for immobility. We chose halothane because the present and previous studies found that cerebral halothane concentrations alone required for producing immobility far exceeded those required in the cord. We also applied the above techniques to another benzene-containing anesthetic, propofol. RESULTS: Prebypass minimum alveolar concentration (MAC) for HFB was 0.82% ± 0.14% (mean ± sd); increased to 2.04% ± 0.8% (P < 0.01) during selective delivery to the cranial circulation; and returned to 0.79% ± 0.28% postbypass. Corresponding values for ODFB were 0.46% ± 0.07%, 0.63% ± 0.12% (P < 0.05), and 0.44% ± 0.10%. ODFB MAC was 0.32% ± 0.17% during selective halothane delivery to brain. But when ODFB was administered to the whole body, MAC was 0.37% ± 0.05%, (NS). Like HFB, the halothane requirement increased threefold when delivered only to the head. In four of five animals, propofol requirements increased by 240%, but in one animal propofol requirements decreased, and the overall change was not statistically significant. CONCLUSIONS: These data suggest that HFB, like halothane, produces immobility, predominantly by a spinal cord action, and that HFB differs from ODFB with respect to brain versus spinal sites of action. Nonetheless, although ODFB can produce immobility via a cerebral action, it also can do this via an independent action in the spinal cord. Thus, our results continue to support the spinal cord as the primary site at which inhaled anesthetics, and perhaps propofol, produce immobility.

AB - BACKGROUND: Previous work demonstrated that isoflurane and halothane act on the spinal cord rather than on the brain to produce immobility in the face of noxious stimulation. These anesthetics share many effects on specific receptors, and thus do not test the broad applicability of the mediation of immobility by the cord. We sought to test such an applicability by determining whether the cord mediated the immobilizing effects of two aromatic anesthetics that differ greatly in their ability to block N-methyl-d-aspartate receptors. METHODS: We investigated the actions of hexafluorobenzene (HFB) and o-difluorobenzene (ODFB) using an intact goat model that allowed selective delivery of anesthetics to the brain. Because our results suggested a significant cerebral effect of ODFB, in other goats we administered halothane 0.5% to the brain, while determining the ODFB concentration delivered to the body (the cord) required for immobility. We chose halothane because the present and previous studies found that cerebral halothane concentrations alone required for producing immobility far exceeded those required in the cord. We also applied the above techniques to another benzene-containing anesthetic, propofol. RESULTS: Prebypass minimum alveolar concentration (MAC) for HFB was 0.82% ± 0.14% (mean ± sd); increased to 2.04% ± 0.8% (P < 0.01) during selective delivery to the cranial circulation; and returned to 0.79% ± 0.28% postbypass. Corresponding values for ODFB were 0.46% ± 0.07%, 0.63% ± 0.12% (P < 0.05), and 0.44% ± 0.10%. ODFB MAC was 0.32% ± 0.17% during selective halothane delivery to brain. But when ODFB was administered to the whole body, MAC was 0.37% ± 0.05%, (NS). Like HFB, the halothane requirement increased threefold when delivered only to the head. In four of five animals, propofol requirements increased by 240%, but in one animal propofol requirements decreased, and the overall change was not statistically significant. CONCLUSIONS: These data suggest that HFB, like halothane, produces immobility, predominantly by a spinal cord action, and that HFB differs from ODFB with respect to brain versus spinal sites of action. Nonetheless, although ODFB can produce immobility via a cerebral action, it also can do this via an independent action in the spinal cord. Thus, our results continue to support the spinal cord as the primary site at which inhaled anesthetics, and perhaps propofol, produce immobility.

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