Nonlinear antagonism of anesthesia in mice by pressure

Previous studies have shown a rectilinear antagonism by pressure of nitrous oxide or isoflurane anesthesia in mice (pressure reversal). Since a rectilinear pressure reversal is predicted by the critical volume hypothesis for anesthesia, we examined this phenomenon with two other gases. We measured the doses of argon or nitrogen which abolished the righting reflex in 50% of animals (ED50) at various high pressures produced by the addition of helium. The ED50 values of argon and nitrogen alone are 16.7 +/- 1.37 and 38.3 +/- 1.62 atmospheres absolute (ATA). Fifty-five percent more argon and 27% more nitrogen is needed to produce anesthesia at 100 ATA. However the increasing anesthetic requirements with pressure were curvilinearly related to pressure, rising most steeply at pressures near the ED50 without helium. This suggests that the pressure reversal of anesthesia is not simply a reciprocal anesthetic expansion-pressure compression phenomenon as predicted by the critical volume hypothesis. It suggests that anesthetics and pressure act at different sites.