Marker entry into vestibular perilymph via the stapes following applications to the round window niche of guinea pigs

Abstract

It has been widely believed that drug entry from the middle ear into perilymph occurs primarily via the round window (RW) membrane. Entry into scala vestibuli (SV) was thought to be dominated by local, inter-scala communication between scala tympani (ST) and SV through permeable tissues such as the spiral ligament. In the present study, the distribution of the ionic marker trimethylphenylammonium (TMPA) was compared following intracochlear injections or applications to the RW niche, with or without occlusion of the RW membrane or stapes area. Perilymph TMPA concentrations were monitored either in real time with TMPA-selective microelectrodes sealed into ST and SV, or by the collection of sequential perilymph samples from the lateral semi-circular canal. Local inter-scala communication of TMPA was confirmed by measuring SV and ST concentrations following direct injections into perilymph of ST. Application of TMPA to the RW niche also showed a predominant entry into ST, with distribution to SV presumed to occur secondarily. When the RW membrane was occluded by a silicone plug, RW niche irrigation produced higher concentrations in SV compared to ST, confirming direct TMPA entry into the vestibule in the region of the stapes. The proportion of TMPA entering by the two routes was quantified by perilymph sampling from the lateral semi-circular canal. The TMPA levels of initial samples (originating from the vestibule) were markedly lower when the stapes area was occluded with silicone. These data were interpreted using a simulation program that incorporates all the major fluid and tissue compartments of the cochlea and vestibular systems. From this analysis it was estimated that 65 % of total TMPA entered through the RW membrane and 35% entered the vestibule directly in the vicinity of the stapes. Direct entry of drugs into the vestibule is relevant to inner ear fluid pharmacokinetics and to the growing field of intratympanic drug delivery.

Selective Window Application of Gentamicin Dexamethasone in Meniere's Disease

“…Different drugs had different results [15,16] . It was reported that application of gentamicin to oval window caused more vestibulotoxicity and hearing loss in Gunea pigs [17] .…”

“…King et al [16] estimated that the rate of gadolinium absorption in the region of stapes was more than 90%. Salt et al [15] showed that trimethylphenylammonium (TMPA) marker was absorbed at a rate of 65% from the round window. Placing gentamicin to the oval window caused a mean increase of 17±22.6 in the caloric weakness.…”

The Auditory Nerve Overlapped Waveform (ANOW) Originates in the Cochlear Apex

“…TTX (250 ng/ml in artificial perilymph) was injected from a pipette sealed into a fenestra at the cochlear apex. The composition of artificial perilymph, in millimolar, was NaCl (127.5), KCl (3.5), NaHCO 3 (25), CaCl 2 (1.3), MgCl 2 (1.2), NaH2PO 4 (0.75), and glucose (11) (Salt et al 2012). Control experiments utilized artificial perilymph without TTX.…”

Development of a drug delivery system for the inner ear using poly(amino acid)-based nanoparticles

“…When a drug reaches the inner ear from the middle ear cavity, it must pass the round window membrane or oval window (Zou et al, 2010;Pyykko et al, 2011). Although there is some controversy regarding which is the dominant route for the inner ear, the round window membrane seems to be superior (Salt et al, 2012). Factors affecting the permeability of a drug through the round window membrane include the size, configuration, concentration, lipid-solubility, and electrical charge of the drug itself, and the thickness of the round window membrane (Goycoolea, 2001).…”