No abstract

In this study, magnetic resonance imaging (MRI) was used to define in vivo the effect of experimental functional obstruction of the eustachian tube (ET) on vascular permeability and the development of middle ear (ME) effusion. After collection of baseline data for ME pressure and MRI, the right tensor veli palatini muscle of 10 cynomolgus monkeys was injected with botulinum toxin A to induce ET obstruction. The left tensor veli palatini muscle was injected with saline in 4 monkeys. Right and left ME pressures and compliances were measured twice daily over a follow-up period of 36 days, and MRI scanning sessions including administration of a contrast agent, gadopentetate dimeglumine, were repeated on days 3, 6, 11, 15, 21, 29, and 36 in 6 animals and on days 15, 21, 29, and 36 in 4 animals. Two right ears did not develop underpressures, 5 developed persistent underpressures, and 3 developed underpressures that resolved. No changes in MRI parameters were noted for the ears that did not develop underpressures, but a progressive brightening of the ME on T2-weighted images, indicative of the development of inflammation and effusion, was noted for the others. Also, an increasing rate of transfer of the contrast agent between the vascular and ME compartments, indicative of increasing vascular permeability, was observed to track the temporal changes in ME pressure. These results support a causal relationship between ET dysfunction, ME underpressures, increased vascular permeability, and otitis media with effusion

Previous studies documented a significant increase in middle ear pressure following intranasal challenges with ascaris antigen or histamine in sensitized cynomolgus monkeys. To confirm that effects and investigate the mechanism, 4 monkeys were intranasally challenged at separate sessions with histamine (10 mg), bradykinin (1, 10 mg) and prostaglandin D2 (PgD2, 0.5, 1.0 mg) and followed for 90 min. Before and after challenge, middle ear pressure, mucosal blood flow, heart rate, blood pressure, body temperature and the partial pressures of O2 and CO2 in the venous blood were measured. The results showed that while bradykinin challenge had no effect on these measures, PgD2 provoked increased middle ear pressure, and histamine resulted in a biphasic pattern of increasing pressures followed by decreasing pressures. The pattern of change in middle ear pressure after histamine challenge was explicable by a mechanism involving transmucosal gas exchange, while that for PgD2 was related to increased mucosal inflammation. These results document the development of positive middle ear pressures during provoked nasal inflammation and may have relevance to similar observations in the clinical setting.

The objective of this study was to determine the effect of middle ear (ME) gas composition on eustachian tube ventilatory function (ETVF). ETVF was evaluated by using forced-response and inflation-de-flation tests in four alert cynomolgus monkeys during test sessions with different gas compositions. The ME was flushed with one of the four gas mixtures: 1. air; 2. 12% oxygen, 88% nitrogen; 3. 100% oxygen; and 4. 5% carbon dioxide, 21% oxygen, and 74% nitrogen before and during testing. The results documented lower opening, steady-state, and closing pressures, lower passive and active resistance, and greater dilatory efficiency following ME flushes with the hypercarbic and hypoxic gas mixtures when compared to the others. Also, for applied ME overpressure, the maximum pressure change during a swallow, the average pressure drop for all swallows, and the percentage of the applied pressure equalized were greater under hypoxic and hypercarbic conditions. These results show that ME gas composition affects ETVF and support feedback modulation of ME pressure regulation.