Nitric oxide and prostanoids contribute to isoflurane-induced cerebral hyperemia in pigs

L. E. Moore, Jeffrey Kirsch, M. A. Helfaer, J. R. Tobin, R. W. McPherson, R. J. Traystman

Research output: Contribution to journalArticle

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Abstract

Background: The mechanism of isoflurane-induced cerebral hyperemia is poorly understood. Data from studies in vitro suggest that volatile anesthetics release a vasodilator prostanoid. We hypothesized that prostanoids and nitric oxide (NO) are mediators of this response in vivo. If true, inhibition of cyclooxygenase by indomethacin (5 mg/kg intravenously) or of nitric oxide synthase by N(ω)-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg intravenously) should attenuate isoflurane-induced hyperemia. Any response to L-NAME occurring via nitric oxide should be competitively reversed by L-arginine. Methods: The cerebral blood flow (microsphere) response to 1 MAC isoflurane was tested at three time points (0, 90, and 180 min) in pentobarbital-anesthetized pigs. Isoflurane challenges were separated by 60-min periods of continuous intravenous pentobarbital alone. Control animals (n = 7) received no additional pharmacologic intervention. Experimental animals were randomized to receive L-NAME before the second and indomethacin before the third isoflurane challenge (n = 7); L-NAME before the second and L-arginine (400 mg/kg intravenously) before the third isoflurane challenge (n = 9); or indomethacin before the second and L-NAME before the third isoflurane challenge (n = 8). Results: In control animals, isoflurane reproducibly increased cerebral blood flow (whole brain; 113 ± 18%, 120 ± 18%, and 103 ± 19% increase above baseline at each time point, respectively). Both indomethacin and L-NAME attenuated (10 ± 10% and 52 ± 11% increase, respectively) the hyperemic response to isoflurane. The effect of L-NAME was reversed by L-arginine. Conclusions: We conclude that both prostanoids and nitric oxide contribute to isoflurane-induced hyperemia. We are unable to determine from our data what, if any, interaction exists between these two mechanisms.

Original languageEnglish (US)
Pages (from-to)1328-1337
Number of pages10
JournalAnesthesiology
Volume80
Issue number6
StatePublished - 1994
Externally publishedYes

Fingerprint

Isoflurane
Hyperemia
Prostaglandins
Nitric Oxide
Swine
NG-Nitroarginine Methyl Ester
Indomethacin
Cerebrovascular Circulation
Arginine
Pentobarbital
Prostaglandin-Endoperoxide Synthases
Vasodilator Agents
Microspheres
Nitric Oxide Synthase
Anesthetics

Keywords

  • Anesthetics, gases: nitric oxide
  • Anesthetics, volatile: isoflurane
  • Brain: cerebral blood flow; cerebral metabolic rate of oxygen consumption
  • Inhibitors, cyclooxygenase: indomethacin
  • Vasodilation: endothelium-dependent
  • Vasodilators: prostanoids

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Moore, L. E., Kirsch, J., Helfaer, M. A., Tobin, J. R., McPherson, R. W., & Traystman, R. J. (1994). Nitric oxide and prostanoids contribute to isoflurane-induced cerebral hyperemia in pigs. Anesthesiology, 80(6), 1328-1337.

Nitric oxide and prostanoids contribute to isoflurane-induced cerebral hyperemia in pigs. / Moore, L. E.; Kirsch, Jeffrey; Helfaer, M. A.; Tobin, J. R.; McPherson, R. W.; Traystman, R. J.

In: Anesthesiology, Vol. 80, No. 6, 1994, p. 1328-1337.

Research output: Contribution to journalArticle

Moore, LE, Kirsch, J, Helfaer, MA, Tobin, JR, McPherson, RW & Traystman, RJ 1994, 'Nitric oxide and prostanoids contribute to isoflurane-induced cerebral hyperemia in pigs', Anesthesiology, vol. 80, no. 6, pp. 1328-1337.
Moore LE, Kirsch J, Helfaer MA, Tobin JR, McPherson RW, Traystman RJ. Nitric oxide and prostanoids contribute to isoflurane-induced cerebral hyperemia in pigs. Anesthesiology. 1994;80(6):1328-1337.
Moore, L. E. ; Kirsch, Jeffrey ; Helfaer, M. A. ; Tobin, J. R. ; McPherson, R. W. ; Traystman, R. J. / Nitric oxide and prostanoids contribute to isoflurane-induced cerebral hyperemia in pigs. In: Anesthesiology. 1994 ; Vol. 80, No. 6. pp. 1328-1337.
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abstract = "Background: The mechanism of isoflurane-induced cerebral hyperemia is poorly understood. Data from studies in vitro suggest that volatile anesthetics release a vasodilator prostanoid. We hypothesized that prostanoids and nitric oxide (NO) are mediators of this response in vivo. If true, inhibition of cyclooxygenase by indomethacin (5 mg/kg intravenously) or of nitric oxide synthase by N(ω)-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg intravenously) should attenuate isoflurane-induced hyperemia. Any response to L-NAME occurring via nitric oxide should be competitively reversed by L-arginine. Methods: The cerebral blood flow (microsphere) response to 1 MAC isoflurane was tested at three time points (0, 90, and 180 min) in pentobarbital-anesthetized pigs. Isoflurane challenges were separated by 60-min periods of continuous intravenous pentobarbital alone. Control animals (n = 7) received no additional pharmacologic intervention. Experimental animals were randomized to receive L-NAME before the second and indomethacin before the third isoflurane challenge (n = 7); L-NAME before the second and L-arginine (400 mg/kg intravenously) before the third isoflurane challenge (n = 9); or indomethacin before the second and L-NAME before the third isoflurane challenge (n = 8). Results: In control animals, isoflurane reproducibly increased cerebral blood flow (whole brain; 113 ± 18{\%}, 120 ± 18{\%}, and 103 ± 19{\%} increase above baseline at each time point, respectively). Both indomethacin and L-NAME attenuated (10 ± 10{\%} and 52 ± 11{\%} increase, respectively) the hyperemic response to isoflurane. The effect of L-NAME was reversed by L-arginine. Conclusions: We conclude that both prostanoids and nitric oxide contribute to isoflurane-induced hyperemia. We are unable to determine from our data what, if any, interaction exists between these two mechanisms.",
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T1 - Nitric oxide and prostanoids contribute to isoflurane-induced cerebral hyperemia in pigs

AU - Moore, L. E.

AU - Kirsch, Jeffrey

AU - Helfaer, M. A.

AU - Tobin, J. R.

AU - McPherson, R. W.

AU - Traystman, R. J.

PY - 1994

Y1 - 1994

N2 - Background: The mechanism of isoflurane-induced cerebral hyperemia is poorly understood. Data from studies in vitro suggest that volatile anesthetics release a vasodilator prostanoid. We hypothesized that prostanoids and nitric oxide (NO) are mediators of this response in vivo. If true, inhibition of cyclooxygenase by indomethacin (5 mg/kg intravenously) or of nitric oxide synthase by N(ω)-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg intravenously) should attenuate isoflurane-induced hyperemia. Any response to L-NAME occurring via nitric oxide should be competitively reversed by L-arginine. Methods: The cerebral blood flow (microsphere) response to 1 MAC isoflurane was tested at three time points (0, 90, and 180 min) in pentobarbital-anesthetized pigs. Isoflurane challenges were separated by 60-min periods of continuous intravenous pentobarbital alone. Control animals (n = 7) received no additional pharmacologic intervention. Experimental animals were randomized to receive L-NAME before the second and indomethacin before the third isoflurane challenge (n = 7); L-NAME before the second and L-arginine (400 mg/kg intravenously) before the third isoflurane challenge (n = 9); or indomethacin before the second and L-NAME before the third isoflurane challenge (n = 8). Results: In control animals, isoflurane reproducibly increased cerebral blood flow (whole brain; 113 ± 18%, 120 ± 18%, and 103 ± 19% increase above baseline at each time point, respectively). Both indomethacin and L-NAME attenuated (10 ± 10% and 52 ± 11% increase, respectively) the hyperemic response to isoflurane. The effect of L-NAME was reversed by L-arginine. Conclusions: We conclude that both prostanoids and nitric oxide contribute to isoflurane-induced hyperemia. We are unable to determine from our data what, if any, interaction exists between these two mechanisms.

AB - Background: The mechanism of isoflurane-induced cerebral hyperemia is poorly understood. Data from studies in vitro suggest that volatile anesthetics release a vasodilator prostanoid. We hypothesized that prostanoids and nitric oxide (NO) are mediators of this response in vivo. If true, inhibition of cyclooxygenase by indomethacin (5 mg/kg intravenously) or of nitric oxide synthase by N(ω)-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg intravenously) should attenuate isoflurane-induced hyperemia. Any response to L-NAME occurring via nitric oxide should be competitively reversed by L-arginine. Methods: The cerebral blood flow (microsphere) response to 1 MAC isoflurane was tested at three time points (0, 90, and 180 min) in pentobarbital-anesthetized pigs. Isoflurane challenges were separated by 60-min periods of continuous intravenous pentobarbital alone. Control animals (n = 7) received no additional pharmacologic intervention. Experimental animals were randomized to receive L-NAME before the second and indomethacin before the third isoflurane challenge (n = 7); L-NAME before the second and L-arginine (400 mg/kg intravenously) before the third isoflurane challenge (n = 9); or indomethacin before the second and L-NAME before the third isoflurane challenge (n = 8). Results: In control animals, isoflurane reproducibly increased cerebral blood flow (whole brain; 113 ± 18%, 120 ± 18%, and 103 ± 19% increase above baseline at each time point, respectively). Both indomethacin and L-NAME attenuated (10 ± 10% and 52 ± 11% increase, respectively) the hyperemic response to isoflurane. The effect of L-NAME was reversed by L-arginine. Conclusions: We conclude that both prostanoids and nitric oxide contribute to isoflurane-induced hyperemia. We are unable to determine from our data what, if any, interaction exists between these two mechanisms.

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KW - Brain: cerebral blood flow; cerebral metabolic rate of oxygen consumption

KW - Inhibitors, cyclooxygenase: indomethacin

KW - Vasodilation: endothelium-dependent

KW - Vasodilators: prostanoids

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