MEMBRANE EXPANSION AND INHALATION ANESTHETICS - MEAN EXCESS VOLUME HYPOTHESIS

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 25  (1) , 123-130
Abstract
High-precision solution densimetry was used to determine volume parameters for the interaction of inhalation anesthetics with water, nonpolar solvent and phospholipid vesicles. The precision of the densimeter is mainly limited by the constancy of the temperature during measurement. Temperature stability was maintained within .+-. 0.0005.degree. and monitored by a microprocessor-controlled Thermistor thermometer with 0.0001.degree. resolution. All values were obtained at 25.degree.. Because volatile anesthetics in liquid form usually contain water, they were purified by passage through activated Al2O3 columns. The molal volumes of dried preparations at the pure liquid states were halothane, 106.33; isoflurane, 123.66 and enflurane, 121.99 cm3/mol at 298.150.degree. K. The mean molal excess volumes of anesthetic-water mixtures were negative at dilute anesthetic concentrations in water and positive at dilute water concentrations in liquid anesthetics. These values were dependent on the mol fractions of each component and showed a minimum in the water-rich region and a maximum in the anesthetic-rich region. In water, the partial molal volumes were halothane 93.7, isoflurane 103.4 and enflurane 98.6 cm3/mol at infinite dilution, and increased as the anesthetic concentration was increased. The partial molal volumes of water in liquid anesthetics were in halothane 21.7, isoflurane 21.0 and enflurane 20.5 cm3/mol at infinite dilution, and decreased as the anesthetic concentration was decreased. The mean excess volumes of the anesthetic-decane mixture were positive in the entire mixing range. The partial molal volumes of anesthetics in n-decane at infinite dilution were halothane 114.9, isoflurane 135.3 and enflurane 135.2 cm3/mol. The mean specific excess volumes of the mixture of anesthetics and dimyristoylphosphatidylcholine vesicle suspension showed positive values. The partial molal volume was not evaluated because of the theoretical difficulty in estimating it in a dispersed 2-phase system. Because the mean excess volume of anesthetics dissolved in water is always negative and that incorporated into phospholipid suspension is positive, anesthetics expand the total volume of the model membrane system when translocated from water to the membrane. Anesthesia occurs when the mean excess volume of the total system exceeds a limiting value, and the bulk membrane size is irrelevant. Although the present result in no way disclaims alternative hypotheses, it demonstrates that the pressure reversal of anesthesia can be explained without assuming any specific receptors for these anesthetics.