We used intravital fluorescent microscopy coupled with computerized video image processing to examine the cochlear microvasculature. In Mongolian gerbils the bulla was opened ventrally and a small window was made in the second turn of the cochlea. After fluorescein isothiocyanate-dextran administration, the radiating arterioles were video-recorded under X675 magnification. Computer determinations of arteriolar response to norepinephrine bitartrate (mixed alpha 1/alpha 2 agonist), phenylephrine hydrochloride (alpha 1 agonist), and UK 14,304 tartrate (alpha 2 agonist) were made at multiple dose levels over time. Findings were consistent with arteriolar constriction in response to alpha-adrenergic stimulation. The presence of alpha 1 and alpha 2 receptors was established, and a predominance of alpha 2 receptors in the cochlea was suggested.
In a rat model, we investigated the role of tumor necrosis factor (TNF) and interleukin-1 (IL-1) in endotoxin-induced middle ear effusions (MEEs). After the eustachian tube was obstructed, the middle ear was transtympanically injected with 35 microL of either 1) 1 mg/ mL lipopolysaccharide (LPS); 2) LPS and 100 micrograms TNF binding protein (TNFbp); 3) LPS and 1 microgram IL-1 receptor antagonist (IL-1ra); or 4) LPS, TNFbp, and IL-1ra. Every 2 hours, the fluid within the middle ear was collected, and the quantity of albumin in the fluid, an index of vascular leakage, was determined by enzyme-linked immunosorbent assay. After 6 hours, the middle ear was fixed for histologic analysis. The TNFbp significantly attenuated vascular extravasation into the middle ear. The IL-1ra did not significantly alter effusion development. These results indicate that TNF, but not IL-1, is a mediator of LPS-induced MEE. Therefore, TNFbp may represent a novel approach to the treatment of otitis media with effusion.
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