Directional Asymmetry in the Measured Nitrous Oxide Time Constant for Middle Ear Transmucosal Gas Exchange

Abstract

Simple, 2-compartment mathematical models of middle ear (ME) transmucosal gas exchange reproduce observed ME pressure behavior. These models require input of an experimentally determined, lumped-parameter exchange constant for each represented gas species. Previous model applications assumed directional asymmetry for those parameters, which has not been experimentally validated. As a surrogate for the inert gas nitrogen (N2), for which exchange is too slow to be measurable, the nitrous oxide (N2O) transmucosal exchange constant for 16 ears of 8 monkeys was measured for positive and negative ME blood N20 gradients. The paired exchange constants for each ear were highly correlated, but the ME-blood/blood-ME exchange constant ratio was approximately 13. Modeling shows this asymmetry to depend on the value of the arterial-venous/arterialME ratio, a variable in the exchange constant for perfusion-limited gases. These results support an asymmetric rate of transmucosal N20 and, by extension, N2 exchange for the ME. Because the primary controlling parameter for ME pressure behavior in the absence of eustachian tube opening is the rate of transmucosal N2 exchange, this effect needs to be incorporated into the simple 2-compartment exchange models for predictive accuracy. The gradient ratio dependence suggests that parameter-free modeling may require treating the ME mucosa as having a distributed gradient for certain gas species.