Oxymetazoline Applied Topically to the Nasal Mucosa Decreases Trans-Mucosal Nitrous Oxide Exchange for the Middle Ear

Abstract

Objective: Determine if the middle ear (ME) trans-mucosal nitrous oxide (N2O) gas exchange rate can be pharmacologically modulated by the nasal application of a vasoconstrictor. Methods: In a randomized, double-blind, crossover study, 20 adults received a nasal spray challenge containing either oxymetazoline or saline (placebo). At each session, subjects were fitted with a non-rebreathing mask and breathed room air for 20 minutes, 50% N2O:50% O2 for 20 minutes, and 100% O2 for 10 minutes. Throughout, heart rate, blood pressure (BP), and blood O2 saturation were monitored, and bilateral ME pressure was recorded by tympanometry every minute. The primary outcome measure was the slope of the ME pressure-time function for the experimental period, a direct measure of the transMEM N2O exchange constant. The effects of treatment, session, and period on the measured vital signs and of treatment, session, disease history, and ear on the ME pressure-time slopes were evaluated for statistical significance using repeated measures ANOVAs. Results: The analysis documented a significant effect of period on O2 saturation (N2O > room air, P = .03) and of treatment on blood pressure (oxymetazoline > placebo, P < .02) and the ME pressure-time slope (placebo > oxymetazoline, P = .05). Conclusion: The exchange rate across the ME mucosa of inert gases can be decreased by topical treatment of the nasal mucosa with oxymetazoline.

A formal description of middle ear pressure-regulation

“…Simulations 5 and 6 predict that a downgraded ET opening efficiency will be expressed as a less efficient MEPR for those periods which is accompanied by a consequent negative shift in the EV-MEEPG, effects validated by the change in MEEPG (tympanometric pressure) observed for children and adults during natural and experimental upper respiratory viral infections (Antonio et al, 2002; Buchman et al, 1995; Moody et al, 1998). In addition, emergent features of the model such as physiologic ME species-pressures (Simulation 6), the negative EV-MEEPG for all ET opening efficiencies not equal to 1 (Simulation 3), and the perfusion-limitation on the rate of MEEPG change (Simulations 2, 3) are consistent with clinical measurement (Antonio et al, 2002; Felding et al, 1987; Hergils et al, 1990; Hergils et al, 1997; Moody et al, 1998; Sade et al, 1993) and experimental results (Buchman et al, 1995; Teixeira et al, 2015; Teixeira et al, 2016). …”

Histamine Applied Topically to the Nasal Mucosa Increases the Transmucosal Nitrous Oxide Exchange for the Middle Ear

“…Because the post-challenge ME pressure trajectory is the main outcome variable for the present study, we considered the possibility that the pattern of ME pressure increase observed here signaled a change in MEM volume and not an increased MEM blood perfusion rate. However, we discounted that data interpretation because, 1) MEM swelling occurs quickly which would cause a rapid ME pressure response that is not consistent with the slow, progressive increase that characterized our data, 2) mathematical simulations of the experiment show that any reasonable change in MEM volume would have a very small effect on ME pressure, and 3) past experiments that used a similar design format and vasoactive agents to drive the response reported changes in the ME pressure trajectory similar to that observed in the present study 12,13 .…”

“…The unified airway response predicts that regional application of a noxious, inflammatory stimulus will provoke both local and distal mucosal inflammation. Here, topical application of histamine to the nasal mucosa was used as the regional stimulus 16,18 and the trans-MEM N 2 O exchange-rate, a direct measure of the MEM blood perfusion rate 10 , was measured as the distal inflammatory response 12,13 . The confounding effect of ET openings on that response measure were reduced by reclining the subjects to decrease ET opening efficiency and instructing them to limit “swallowing” during the period of data collection, and eliminated by restricting the data analysis to time periods with no evidence of active or passive ET openings.…”

“…This was a randomized, double-blind, placebo-controlled, cross-over study requiring that participants complete paired N 2 O breathing sessions at a minimum 1-week interval 12,13 . Prior to subject entry, a pharmacist prepared the two challenge materials according to a randomization code and supplied them to the investigators as identical intranasal atomization devices (LMA MAD Nasal, Wolfe-Tory Medical Inc, Salt Lake City, UT) labeled only with session and subject numbers.…”

“…In this experiment, we used histamine challenge of the nasal mucosa 19 in the context of a previously described placebo-controlled, double-blind, crossover protocol 12,13 to test the hypothesis that the trans-MEM N 2 O exchange rate for humans is increased by histamine-provoked nasal inflammation, an expression consistent with expectations under the unified airway model.…”