Halothane and isoflurane increase pulmonary artery endothelial cell sensitivity to oxidant-mediated injury

Jay R. Shayevitz, J. Varani, P. A. Ward, P. R. Knight

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Volatile anesthetics inhibit phagocytic cell function, yet little is known about their effects on target tissues or on the target tissue response to stimulated phagocytes. Experiments were performed to determine how exposure to halothane and isoflurane changes rat pulmonary artery endothelial cell (RPAEC) viability in response to the toxic oxygen metabolites produced by stimulated phagocytic cells. RPAECs were grown in monolayer culture. The monolayers were treated with phorbol myristate acetate (PMA) -stimulated human neutrophils at an effector-to-target ratio of 20:1 after equilibration with 0.4% or 1.7% halothane or 0.7% or 2.8% isoflurane. As measured by percent-specific release of incorporated 51Cr label (mean ± SE), cytotoxicity in the presence of 1.7% halothane (75.3 ± 3.4%) was significantly greater (P < 0.02) than cytotoxicity in 5% CO2 in air (44.7 ± 3.3%) and in 0.4% halothane (57.3 ± 4.7%). Also, cytotoxicity in 1.7% halothane was significantly greater than in 0.4% halothane (P < 0.02). The authors found that RPAECs incubated in isoflurane exhibited significantly greater release of 51Cr than cells incubated in the MAC equivalent concentrations of halothane: 78.2 ± 2.6% in 0.7% isoflurane (P = 0.0004) and 83.8 ± 1% in 2.8% isoflurane (P = 0.005). Because early neutrophil cytotoxicity has been found to be mediated primarily by hydroxyl radical (HO·) and hydrogen peroxide (H2O2), the authors measured H2O2 production by similar numbers of PMA-stimulated neutrophils under similar exposure conditions. In carrier gas, PMA-stimulated neutrophils produced 20.5 ± 1.3 nmol H2O2·106 cells-1·h-1. At the higher concentrations of halothane, H2O2 production actually was inhibited in comparison with carrier gas (15.4 ± 1.4 nmol H2O2·106 cells-1·h-1 in 1.7% halothane and 16.8 ± 0.8 in 2.8% halothane), but the degree of inhibition did not reach statistical significance. In isoflurane, however, H2O2 production was not different from that seen in carrier gas. In other experiments, the monolayers were treated with 0, 200, 500, and 1,000 μM H2O2 after equilibration with 0.4%, 1.7%, and 2.8% halothane or 0.7%, 2.8%, and 5% isoflurane in 5% CO2 in air. Efficiency of replating was used to measure degree of injury. Both halothane and isoflurane enhance the sensitivity of the RPAEC monolayers to injury by H2O2. The sensitizing effect of halothane was reversed by removing the anesthetic. Halothane and isoflurane thus enhance RPAEC sensitivity to injury by both H2O2 and PMA-stimulated neutrophils. In increasing RPAEC sensitivity to injury by oxygen metabolites, halothane and isoflurane may be inhibiting processes involved in intracellular antioxidant defenses. Use of volatile anesthetics in patients at risk for oxidant-mediated end-organ injury thus may enhance the magnitude of such injuries.

Original languageEnglish (US)
Pages (from-to)1067-1077
Number of pages11
JournalAnesthesiology
Volume74
Issue number6
StatePublished - 1991
Externally publishedYes

Fingerprint

Isoflurane
Halothane
Oxidants
Pulmonary Artery
Endothelial Cells
Wounds and Injuries
Tetradecanoylphorbol Acetate
Neutrophils
Phagocytes
Anesthetics
Gases
Air
Oxygen
Poisons
Hydroxyl Radical
Hydrogen Peroxide

Keywords

  • Anesthetics, volatile
  • Cytotoxicity
  • Halothane
  • Hydrogen peroxide
  • Isoflurane
  • Lung
  • Pulmonary artery endothelium
  • Superoxide

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Halothane and isoflurane increase pulmonary artery endothelial cell sensitivity to oxidant-mediated injury. / Shayevitz, Jay R.; Varani, J.; Ward, P. A.; Knight, P. R.

In: Anesthesiology, Vol. 74, No. 6, 1991, p. 1067-1077.

Research output: Contribution to journalArticle

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abstract = "Volatile anesthetics inhibit phagocytic cell function, yet little is known about their effects on target tissues or on the target tissue response to stimulated phagocytes. Experiments were performed to determine how exposure to halothane and isoflurane changes rat pulmonary artery endothelial cell (RPAEC) viability in response to the toxic oxygen metabolites produced by stimulated phagocytic cells. RPAECs were grown in monolayer culture. The monolayers were treated with phorbol myristate acetate (PMA) -stimulated human neutrophils at an effector-to-target ratio of 20:1 after equilibration with 0.4{\%} or 1.7{\%} halothane or 0.7{\%} or 2.8{\%} isoflurane. As measured by percent-specific release of incorporated 51Cr label (mean ± SE), cytotoxicity in the presence of 1.7{\%} halothane (75.3 ± 3.4{\%}) was significantly greater (P < 0.02) than cytotoxicity in 5{\%} CO2 in air (44.7 ± 3.3{\%}) and in 0.4{\%} halothane (57.3 ± 4.7{\%}). Also, cytotoxicity in 1.7{\%} halothane was significantly greater than in 0.4{\%} halothane (P < 0.02). The authors found that RPAECs incubated in isoflurane exhibited significantly greater release of 51Cr than cells incubated in the MAC equivalent concentrations of halothane: 78.2 ± 2.6{\%} in 0.7{\%} isoflurane (P = 0.0004) and 83.8 ± 1{\%} in 2.8{\%} isoflurane (P = 0.005). Because early neutrophil cytotoxicity has been found to be mediated primarily by hydroxyl radical (HO·) and hydrogen peroxide (H2O2), the authors measured H2O2 production by similar numbers of PMA-stimulated neutrophils under similar exposure conditions. In carrier gas, PMA-stimulated neutrophils produced 20.5 ± 1.3 nmol H2O2·106 cells-1·h-1. At the higher concentrations of halothane, H2O2 production actually was inhibited in comparison with carrier gas (15.4 ± 1.4 nmol H2O2·106 cells-1·h-1 in 1.7{\%} halothane and 16.8 ± 0.8 in 2.8{\%} halothane), but the degree of inhibition did not reach statistical significance. In isoflurane, however, H2O2 production was not different from that seen in carrier gas. In other experiments, the monolayers were treated with 0, 200, 500, and 1,000 μM H2O2 after equilibration with 0.4{\%}, 1.7{\%}, and 2.8{\%} halothane or 0.7{\%}, 2.8{\%}, and 5{\%} isoflurane in 5{\%} CO2 in air. Efficiency of replating was used to measure degree of injury. Both halothane and isoflurane enhance the sensitivity of the RPAEC monolayers to injury by H2O2. The sensitizing effect of halothane was reversed by removing the anesthetic. Halothane and isoflurane thus enhance RPAEC sensitivity to injury by both H2O2 and PMA-stimulated neutrophils. In increasing RPAEC sensitivity to injury by oxygen metabolites, halothane and isoflurane may be inhibiting processes involved in intracellular antioxidant defenses. Use of volatile anesthetics in patients at risk for oxidant-mediated end-organ injury thus may enhance the magnitude of such injuries.",
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T1 - Halothane and isoflurane increase pulmonary artery endothelial cell sensitivity to oxidant-mediated injury

AU - Shayevitz, Jay R.

AU - Varani, J.

AU - Ward, P. A.

AU - Knight, P. R.

PY - 1991

Y1 - 1991

N2 - Volatile anesthetics inhibit phagocytic cell function, yet little is known about their effects on target tissues or on the target tissue response to stimulated phagocytes. Experiments were performed to determine how exposure to halothane and isoflurane changes rat pulmonary artery endothelial cell (RPAEC) viability in response to the toxic oxygen metabolites produced by stimulated phagocytic cells. RPAECs were grown in monolayer culture. The monolayers were treated with phorbol myristate acetate (PMA) -stimulated human neutrophils at an effector-to-target ratio of 20:1 after equilibration with 0.4% or 1.7% halothane or 0.7% or 2.8% isoflurane. As measured by percent-specific release of incorporated 51Cr label (mean ± SE), cytotoxicity in the presence of 1.7% halothane (75.3 ± 3.4%) was significantly greater (P < 0.02) than cytotoxicity in 5% CO2 in air (44.7 ± 3.3%) and in 0.4% halothane (57.3 ± 4.7%). Also, cytotoxicity in 1.7% halothane was significantly greater than in 0.4% halothane (P < 0.02). The authors found that RPAECs incubated in isoflurane exhibited significantly greater release of 51Cr than cells incubated in the MAC equivalent concentrations of halothane: 78.2 ± 2.6% in 0.7% isoflurane (P = 0.0004) and 83.8 ± 1% in 2.8% isoflurane (P = 0.005). Because early neutrophil cytotoxicity has been found to be mediated primarily by hydroxyl radical (HO·) and hydrogen peroxide (H2O2), the authors measured H2O2 production by similar numbers of PMA-stimulated neutrophils under similar exposure conditions. In carrier gas, PMA-stimulated neutrophils produced 20.5 ± 1.3 nmol H2O2·106 cells-1·h-1. At the higher concentrations of halothane, H2O2 production actually was inhibited in comparison with carrier gas (15.4 ± 1.4 nmol H2O2·106 cells-1·h-1 in 1.7% halothane and 16.8 ± 0.8 in 2.8% halothane), but the degree of inhibition did not reach statistical significance. In isoflurane, however, H2O2 production was not different from that seen in carrier gas. In other experiments, the monolayers were treated with 0, 200, 500, and 1,000 μM H2O2 after equilibration with 0.4%, 1.7%, and 2.8% halothane or 0.7%, 2.8%, and 5% isoflurane in 5% CO2 in air. Efficiency of replating was used to measure degree of injury. Both halothane and isoflurane enhance the sensitivity of the RPAEC monolayers to injury by H2O2. The sensitizing effect of halothane was reversed by removing the anesthetic. Halothane and isoflurane thus enhance RPAEC sensitivity to injury by both H2O2 and PMA-stimulated neutrophils. In increasing RPAEC sensitivity to injury by oxygen metabolites, halothane and isoflurane may be inhibiting processes involved in intracellular antioxidant defenses. Use of volatile anesthetics in patients at risk for oxidant-mediated end-organ injury thus may enhance the magnitude of such injuries.

AB - Volatile anesthetics inhibit phagocytic cell function, yet little is known about their effects on target tissues or on the target tissue response to stimulated phagocytes. Experiments were performed to determine how exposure to halothane and isoflurane changes rat pulmonary artery endothelial cell (RPAEC) viability in response to the toxic oxygen metabolites produced by stimulated phagocytic cells. RPAECs were grown in monolayer culture. The monolayers were treated with phorbol myristate acetate (PMA) -stimulated human neutrophils at an effector-to-target ratio of 20:1 after equilibration with 0.4% or 1.7% halothane or 0.7% or 2.8% isoflurane. As measured by percent-specific release of incorporated 51Cr label (mean ± SE), cytotoxicity in the presence of 1.7% halothane (75.3 ± 3.4%) was significantly greater (P < 0.02) than cytotoxicity in 5% CO2 in air (44.7 ± 3.3%) and in 0.4% halothane (57.3 ± 4.7%). Also, cytotoxicity in 1.7% halothane was significantly greater than in 0.4% halothane (P < 0.02). The authors found that RPAECs incubated in isoflurane exhibited significantly greater release of 51Cr than cells incubated in the MAC equivalent concentrations of halothane: 78.2 ± 2.6% in 0.7% isoflurane (P = 0.0004) and 83.8 ± 1% in 2.8% isoflurane (P = 0.005). Because early neutrophil cytotoxicity has been found to be mediated primarily by hydroxyl radical (HO·) and hydrogen peroxide (H2O2), the authors measured H2O2 production by similar numbers of PMA-stimulated neutrophils under similar exposure conditions. In carrier gas, PMA-stimulated neutrophils produced 20.5 ± 1.3 nmol H2O2·106 cells-1·h-1. At the higher concentrations of halothane, H2O2 production actually was inhibited in comparison with carrier gas (15.4 ± 1.4 nmol H2O2·106 cells-1·h-1 in 1.7% halothane and 16.8 ± 0.8 in 2.8% halothane), but the degree of inhibition did not reach statistical significance. In isoflurane, however, H2O2 production was not different from that seen in carrier gas. In other experiments, the monolayers were treated with 0, 200, 500, and 1,000 μM H2O2 after equilibration with 0.4%, 1.7%, and 2.8% halothane or 0.7%, 2.8%, and 5% isoflurane in 5% CO2 in air. Efficiency of replating was used to measure degree of injury. Both halothane and isoflurane enhance the sensitivity of the RPAEC monolayers to injury by H2O2. The sensitizing effect of halothane was reversed by removing the anesthetic. Halothane and isoflurane thus enhance RPAEC sensitivity to injury by both H2O2 and PMA-stimulated neutrophils. In increasing RPAEC sensitivity to injury by oxygen metabolites, halothane and isoflurane may be inhibiting processes involved in intracellular antioxidant defenses. Use of volatile anesthetics in patients at risk for oxidant-mediated end-organ injury thus may enhance the magnitude of such injuries.

KW - Anesthetics, volatile

KW - Cytotoxicity

KW - Halothane

KW - Hydrogen peroxide

KW - Isoflurane

KW - Lung

KW - Pulmonary artery endothelium

KW - Superoxide

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