Acute endolymphatic hydrops generated by exposure of the ear to nontraumatic low-frequency tones

Abstract

Low-frequency sounds presented at high nontraumatizing levels induce temporary hyperacusis in humans and animals. One explanation of this finding is that the basilar membrane operating point may be disturbed by an endolymph volume change. This possibility was investigated using volume and flow markers iontophoresed into the endolymphatic space of guinea pigs. Marker concentrations were measured with ion-selective microelectrodes placed apically and basally to the iontophoresis site during exposure of the ear to low-frequency tones. Concentration changes were interpreted quantitatively using a finite-element model of the endolymphatic space that allowed changes of endolymph cross-sectional area and flow to be derived. Stimulation with a 200 Hz tone at 115 dB SPL for 3 min produced marker concentration changes consistent with the induction of transient endolymphatic hydrops and a basally directed displacement of endolymph. Endocochlear potentials were greater than normal after the exposure when hydrops was present. During identical tone exposures of animals without marker, we found that action potential (AP) threshold changes and endolymph potassium changes associated with the hydropic state were small. Marker concentration changes were compared with changes in endocochlear potential and AP thresholds for a range of exposure frequencies and levels. AP hypersensitivity occurred with 200 Hz exposure levels below those inducing endolymph volume disturbances. Endolymph volume changes are thought to be the result of, rather than the cause of, changes in operating point of the cochlear transducer. The observations that auditory threshold and endolymph potassium changes are minimal under conditions where substantial endolymphatic hydrops is present is relevant to our understanding of the hearing loss in patients with Meniere's disease.

Figure 1

Schematic of the location of electrodes in the cochlea, shown here uncoiled with the four turns marked with Roman numerals. The three scalae, scala tympani (ST), scala media (SM), and scala vestibuli (SV), and the ductus reunions (DR) are indicated. TMA⁺ is injected into scala media by iontophoresis and sets up a concentration profile, as shown in the lower panel, as TMA⁺ diffuses symmetrically away from the injection site. Two ion-selective electrodes are positioned in scala media approximately 0.5 mm basal and 0.5 mm apical to the injection site. Based on the concentration profile shown, longitudinal endolymph movements would cause oppositely directed concentration changes at the two electrodes while cross-sectional area changes would cause similar changes at both electrodes.

Figure 2

Example experiment in which TMA⁺ marker concentration changes were recorded simultaneously from two sites during exposure to 200 Hz tones at different levels. TMA⁺ was injected iontophoretically throughout the experiment starting at zero time, producing a concentration increase that saturates with time. The simultaneously recorded EP measurements are shown in the lower panel. With an exposure level of 115 dB SPL, substantial decreases of marker are produced that are most pronounced at the apical electrode, and EP increases are generated. Stimulation with 125 dB SPL causes even larger TMA⁺ and EP changes.

Figure 3

Cross-sectional area and longitudinal movements of endolymph derived from the data in Figure 2 by simulating the experiment with a finite-element model of the endolymphatic space. Stimulation at levels of 115 dB and higher produce substantial area changes and basally directed displacements of endolymph in the second turn.

Figure 4

Summary of the longitudinal displacements (upper row), cross-sectional area changes (middle row), and endocochlear potential changes (lower row) produced by 3 min stimulation with a 115 dB tone at the four frequencies indicated. Bars indicate standard deviation. The number of observations in each group were 50 Hz:3; 200 Hz: 10; 500 Hz: 4; 1000 Hz:3. The EP data for each experiment was taken as the average of the two traces recorded at the basal and apical electrode locations.

Figure 5

Summary of the magnitude of marker concentration changes seen with exposure to a 200 Hz stimulation for 3 min at varying levels (left panel) and to tones of varying frequency for 3 min at 115 dB SPL (right panel). The concentration present prior to exposure is defined as 100% and the value shown is the minimum TMA⁺ concentration in the period during and following the tone. The recording electrodes were all positioned apical to the TMA⁺ injection site. Bars indicate standard deviation of the number of observations indicated.

Figure 6

Changes of endolymph K⁺ recorded in three experiments during exposure to 200 Hz tones at 115 dB SPL for 3 min as indicated. The mean endolymph K⁺ level prior to stimulation was 151.2 mM (SD 10.3 mM). Bars indicate standard deviation of the normalized change.

Figure 7

Control experiment to test for the possibility that the 200 Hz stimulation caused a “stirring” of scala tympani. Left Prediction from the finite-element model of cochlear fluids in which a second-turn injection (10 mm from base) is simulated with concentration recordings made 0.5 mm from the injection site (9.5 mm from base) and 6 mm from the injection site (4 mm from base, corresponding to a basal turn recording). When the diffusion coefficient was increased by a factor of 10 for 3 min, the marker decreases at the site close to the injection and increases at the distant site. Right A comparable experiment performed in vivo, with simultaneous recordings in the basal and second turn during 200 Hz stimulation. Although the marker decreases in the second turn, no increase in the basal turn is observed, showing that the marker decreases do not occur as a result of endolymph “stirring.”

Figure 8

Control to test for the possibility of sound-induced changes in marker clearance contributing to marker concentration changes. Endolymph displacement (left) and cross-sectional area changes (right) derived from an experiment in which the anionic marker AsF₆⁻ was used are shown to be comparable to those from experiments using TMA⁺. TMA⁺ and AsF₆⁻ have completely different clearance characteristics. TMA⁺ is cleared with a half-time of 30 min, which is incorporated into the analysis, and AsF₆⁻ shows no clearance at all.

Figure 9

Threshold shifts at 8, 4, and 2 kHz and EP changes resulting from 200 Hz tone exposures for 3 min at 115 dB SPL (upper row) and 95 dB SPL (lower row). Bars indicate standard deviation. EP and threshold changes were recorded in different experimental groups.

Figure 10

Summary of the minimum AP thresholds obtained in the period immediately following 200 Hz exposures at levels from 65 to 125 dB SPL. Thresholds were measured at 8, 4, and 2 kHz. Bars indicate standard deviation.