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.
- Anesthetics, volatile
- Hydrogen peroxide
- Pulmonary artery endothelium
ASJC Scopus subject areas
- Anesthesiology and Pain Medicine