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  • Title: Halothane potentiation of hydrogen peroxide-induced inhibition of surfactant synthesis: the role of type II cell energy status.
    Author: Patel AB, Sokolowski J, Davidson BA, Knight PR, Holm BA.
    Journal: Anesth Analg; 2002 Apr; 94(4):943-7, table of contents. PubMed ID: 11916801.
    Abstract:
    UNLABELLED: Small concentrations of inhaled anesthetics can affect Type II cell surfactant production and exacerbate oxidant-mediated lung injury. We hypothesized that inhaled anesthetics augment oxidant-induced Type II pneumocyte dysfunction related to their different effects on cellular adenosine triphosphate (ATP) status. Freshly isolated Type II cells were exposed to different concentrations of hydrogen peroxide (H2O2) in the presence or absence of an in vitro halothane exposure. Cells exposed to 100 microM H2O2 alone demonstrated a 23% decrease in ATP levels and a 32% decrease in phosphatidylcholine (PC) synthesis compared with controls. Halothane alone decreased PC synthesis by only 12% and reduced ATP levels by 20%. However, when exposed to both halothane and H2O2 together, ATP levels decreased by 40%, and PC synthesis rates decreased by 51%. Pretreatment of cells with nicotinamide, an inhibitor of poly adenosine diphosphate ribose polymerase, completely prevented the ATP loss and PC synthesis decline caused by H2O2 alone, but it had no effect on the halothane-augmented portion of the cell injury. These data suggest that the ability of halothane to enhance oxidative damage may be related to its own specific effects on cell energetics that may not be amenable to the same treatments used to mitigate other cellular mechanisms of oxidative stress. IMPLICATIONS: A mediator of inflammation (hydrogen peroxide) and an inhaled anesthetic (halothane) interact to decrease cell energy and secretion of a substance (surfactant) required for healthy lung function from cells that line gas-exchange compartments. This interaction represents a possible mechanism by which inflammatory lung disease may become more severe intraoperatively.
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