Rate of Gas Exchange in the Middle Ear of Guinea Pigs

Abstract

Gas exchange between blood in the middle ear (ME) mucosa and ambient ME gas may be limited by diffusion through tissue or blood perfusion. In order to study the limiting factors in ME gas exchange, a hole was drilled in the bulla of 14 anesthetized guinea pigs through which a mass spectrometer probe was inserted and sealed in place. The rate at which oxygen (O2), carbon dioxide (CO2), nitrogen, and argon concentrations changed toward their steady state values was recorded. From the exponential fitted curves, gas rate constants (Kg) were calculated. The ratio KCO2/KO2 was 4:1, which is lower than expected from a diffusion-limited process in an aqueous compartment. The different rate ratios of CO2 and O2 indicate a diffusion-limited process. However, the deviation of the KCO2/KO2 ratio from that expected in aqueous solutions may indicate the involvement of a lipid compartment in gas exchange or other physiological mechanisms such as local acidity.

Mathematical Model Explaining the Sources of Error in Certain Estimates of the Gas Exchange Constants for the Middle Ear

“…Because the calculation of time constants assumes a closed ME, the model equation attributes the decrease in gas partial pressure caused by venting to transmucosal transfers, thereby artificially inflating the estimated value of the time constants of gases in decreasing magnitude from the most representative to the least representative species. Consequently, experiments that fail to control for this effect will generate downwardly biased estimates of the C02:N2 and C02:02 timeconstant ratios (as was reported by Mover-Lev et al, 19 in comparison to the values reported for monkey experiments) and of the N2:02 time constant ratios (not reported, but consistent with the data presented in the Figure).…”

“…The results of the model simulations document 3 major sources of error in the estimates of the time constants for transmucosal gas exchange presented by Mover-Lev et al 19 The first is a systematic error introduced by the design of the experiment. There, the assumption of a closed ME volume is not consistent with the predicted venting, via the eustachian tube, of gas at total ME pressures in excess of the tubal opening pressure.…”

“…Experiments designed to measure time constants for transmucosal exchange must control for this possible effect by limiting the total ME pressure generated over the course of the experiment to values less than the tubal opening pressure. The model simulation of the experiment shows that this condition most probably was not satisfied for the experiment reported by Mover-Lev et al 19 Figure 3 shows the simulated total ME pressureversus-time function for the experiment reported by Mover-Lev et al 19 The ambient pressure was assumed to be 760 mm Hg for all simulations (though this is arbitrary and does not affect the results), and Figure, greater-than-ambient ME pressure is expected to be generated in this experimental setting. This is caused by the underlying experimental conditions, which create, at the onset of the data collection period, large blood-ME gradients for the fast-exchange gases, C02 (approximately 75 mm Hg) and H20 (approximately 47 mm Hg).…”

“…In simulations using this model, the partial pressures of 02 and CO2 in blood were taken from the data reported in the article by Mover-Lev et al 19 for the steady-state ME pressure of those gases in anesthetized guinea pigs, while those for N2 and H2O were taken from a handbook of physiology. 20 As a first approximation, all blood gas partial pressures were assumed to be constant over the time period modeled.…”

“…1618 More recently, Mover-Lev et al 19 studied transmucosal gas exchange in guinea pigs under conditions of a positive ME-to-blood θ2 pressure gradient and a negative C02 gradient. They reported a ratio for the measured CO2-10-O2 time constants on the order of 3.9 and argued that the respective constants (ie, C02:02 ratio of around 19) reported for the monkey experiments were in error. In the present report, the experimental and analytic methods used by MoverLev et al are shown to calculate inaccurate estimates of the time constants for transmucosal gas exchange because of a failure to control for certain confound- ing effects and to concurrently measure all required system parameters.…”