Effect of volatile anesthetics on hydrogen peroxide-induced injury in aortic and pulmonary arterial endothelial cells

Michael E. Johnson, J. Christopher Sill, Cindy B. Uhl, Teresa J. Halsey, Gregory James Gores

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Oxidant damage to endothelial cells occurs during inflammation and reperfusion after ischemia, mediated in part by endogenously produced hydrogen peroxide (H 2O 2). Previous studies have established a role for increased cytosolic calcium in the mechanism of endothelial oxidant injury, and have suggested that volatile anesthetics may exacerbate oxidant injury in pulmonary endothelium. However, the effect of volatile anesthetics on oxidant injury to systemic arterial endothelial cells, and their effect on oxidant- related changes in cytosolic calcium homeostasis, have not been reported previously. Methods: Primary cultures of human aortic and pulmonary arterial endothelial cells were studied. The rate of cell death after H 2O 2 exposure was determined in cell suspension bypropidium iodide fluorimetry and lactate dehydrogenase release. The final extent of cell death 24 h after H 2O 2 exposure was determined in monolayer cultures by methyl thiazolyl tetrazolium reduction. Cytosolic calcium and cell death were determined in single cells using fura-2 and propidium iodide imaging with digitized, multiparameter, fluorescent video microscopy. Results: In aortic endothelial cells, clinical concentrations of halothane (1.0%) and isoflurane (1.5%) decreased both the rate of cell death and the final extent of cell death after H 2O 2 exposure, with halothane being more protective. Supraclinical concentrations of halothane (2.7%) and isoflurane (4.0%) were less protective. In pulmonary arterial endothelial cells, halothane and isoflurane had essentially no effect on H 2O 2-mediated cell death. The protective effect of anesthetic in aortic endothelial cells was not due to an enhanced removal of H 2O 2 by endogenous enzymes. Hydrogen peroxide exposure caused a large increase in cytosolic calcium well before cell death, and this was moderated by anesthetic treatment. Conclusions: The effect of volatile anesthetics on oxidant injury to endothelial cells may differ between cells derived from systemic and pulmonary vascular beds. Halothane, and to a lesser extent, isoflurane, protects against oxidant injury in aortic endothelial cells. The mechanism of protection may involve modulation of the interaction of H 2O 2 with vital cellular constituents, and/or amelioration of the toxic increase in cytosolic calcium that follows such interaction.

Original languageEnglish (US)
Pages (from-to)103-116
Number of pages14
JournalAnesthesiology
Volume84
Issue number1
DOIs
StatePublished - Jan 1996

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Hydrogen Peroxide
Anesthetics
Oxidants
Endothelial Cells
Cell Death
Halothane
Lung
Isoflurane
Wounds and Injuries
Calcium
Video Microscopy
Fluorometry
Propidium
Fura-2
Poisons
Lung Injury
Iodides
L-Lactate Dehydrogenase
Reperfusion
Endothelium

Keywords

  • Anesthetics, volatile: halothane; isoflurane
  • Blood vessels: aortic; vascular endothelium
  • Hydrogen peroxide: cytotoxicity
  • Ions: calcium influx
  • Lung: pulmonary artery endothelium
  • Reperfusion injury: cell culture

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Effect of volatile anesthetics on hydrogen peroxide-induced injury in aortic and pulmonary arterial endothelial cells. / Johnson, Michael E.; Sill, J. Christopher; Uhl, Cindy B.; Halsey, Teresa J.; Gores, Gregory James.

In: Anesthesiology, Vol. 84, No. 1, 01.1996, p. 103-116.

Research output: Contribution to journalArticle

Johnson, Michael E. ; Sill, J. Christopher ; Uhl, Cindy B. ; Halsey, Teresa J. ; Gores, Gregory James. / Effect of volatile anesthetics on hydrogen peroxide-induced injury in aortic and pulmonary arterial endothelial cells. In: Anesthesiology. 1996 ; Vol. 84, No. 1. pp. 103-116.
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AU - Halsey, Teresa J.

AU - Gores, Gregory James

PY - 1996/1

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N2 - Background: Oxidant damage to endothelial cells occurs during inflammation and reperfusion after ischemia, mediated in part by endogenously produced hydrogen peroxide (H 2O 2). Previous studies have established a role for increased cytosolic calcium in the mechanism of endothelial oxidant injury, and have suggested that volatile anesthetics may exacerbate oxidant injury in pulmonary endothelium. However, the effect of volatile anesthetics on oxidant injury to systemic arterial endothelial cells, and their effect on oxidant- related changes in cytosolic calcium homeostasis, have not been reported previously. Methods: Primary cultures of human aortic and pulmonary arterial endothelial cells were studied. The rate of cell death after H 2O 2 exposure was determined in cell suspension bypropidium iodide fluorimetry and lactate dehydrogenase release. The final extent of cell death 24 h after H 2O 2 exposure was determined in monolayer cultures by methyl thiazolyl tetrazolium reduction. Cytosolic calcium and cell death were determined in single cells using fura-2 and propidium iodide imaging with digitized, multiparameter, fluorescent video microscopy. Results: In aortic endothelial cells, clinical concentrations of halothane (1.0%) and isoflurane (1.5%) decreased both the rate of cell death and the final extent of cell death after H 2O 2 exposure, with halothane being more protective. Supraclinical concentrations of halothane (2.7%) and isoflurane (4.0%) were less protective. In pulmonary arterial endothelial cells, halothane and isoflurane had essentially no effect on H 2O 2-mediated cell death. The protective effect of anesthetic in aortic endothelial cells was not due to an enhanced removal of H 2O 2 by endogenous enzymes. Hydrogen peroxide exposure caused a large increase in cytosolic calcium well before cell death, and this was moderated by anesthetic treatment. Conclusions: The effect of volatile anesthetics on oxidant injury to endothelial cells may differ between cells derived from systemic and pulmonary vascular beds. Halothane, and to a lesser extent, isoflurane, protects against oxidant injury in aortic endothelial cells. The mechanism of protection may involve modulation of the interaction of H 2O 2 with vital cellular constituents, and/or amelioration of the toxic increase in cytosolic calcium that follows such interaction.

AB - Background: Oxidant damage to endothelial cells occurs during inflammation and reperfusion after ischemia, mediated in part by endogenously produced hydrogen peroxide (H 2O 2). Previous studies have established a role for increased cytosolic calcium in the mechanism of endothelial oxidant injury, and have suggested that volatile anesthetics may exacerbate oxidant injury in pulmonary endothelium. However, the effect of volatile anesthetics on oxidant injury to systemic arterial endothelial cells, and their effect on oxidant- related changes in cytosolic calcium homeostasis, have not been reported previously. Methods: Primary cultures of human aortic and pulmonary arterial endothelial cells were studied. The rate of cell death after H 2O 2 exposure was determined in cell suspension bypropidium iodide fluorimetry and lactate dehydrogenase release. The final extent of cell death 24 h after H 2O 2 exposure was determined in monolayer cultures by methyl thiazolyl tetrazolium reduction. Cytosolic calcium and cell death were determined in single cells using fura-2 and propidium iodide imaging with digitized, multiparameter, fluorescent video microscopy. Results: In aortic endothelial cells, clinical concentrations of halothane (1.0%) and isoflurane (1.5%) decreased both the rate of cell death and the final extent of cell death after H 2O 2 exposure, with halothane being more protective. Supraclinical concentrations of halothane (2.7%) and isoflurane (4.0%) were less protective. In pulmonary arterial endothelial cells, halothane and isoflurane had essentially no effect on H 2O 2-mediated cell death. The protective effect of anesthetic in aortic endothelial cells was not due to an enhanced removal of H 2O 2 by endogenous enzymes. Hydrogen peroxide exposure caused a large increase in cytosolic calcium well before cell death, and this was moderated by anesthetic treatment. Conclusions: The effect of volatile anesthetics on oxidant injury to endothelial cells may differ between cells derived from systemic and pulmonary vascular beds. Halothane, and to a lesser extent, isoflurane, protects against oxidant injury in aortic endothelial cells. The mechanism of protection may involve modulation of the interaction of H 2O 2 with vital cellular constituents, and/or amelioration of the toxic increase in cytosolic calcium that follows such interaction.

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KW - Reperfusion injury: cell culture

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