Tetsuo Morizono

Sensorineural Hearing Loss in Otitis Media

Additional evidence is presented to support the hypothesis that both acute purulent otitis media (POM) and chronic suppurative otitis media (COM) can cause high frequency sensorineural hearing loss. In selected patients and in animals (chinchillas) in a pilot study using electrophysiological methods, both temporary threshold shifts and permanent threshold shifts of basal cochlear turn involvement were demonstrated in POM. Data of cochlear involvement in 475 ears with bilateral COM, 607 ears with unilateral COM, and 607 ears serving as controls were obtained from six centers in five countries. In group 1 (15 dB or greater), 43% of ears with unilateral COM and 42% of ears with bilateral COM showed losses, for a combined odds ratio eight times that in controls. In group 2 (30 dB or greater), 16% of ears with unilateral COM and 17% of ears with bilateral COM demonstrated, respectively, seven and ten times that in controls. These statistically significant findings influence clinical considerations.

Electrochemical profiles for monovalent ions in the stria vascularis: Cellular model of ion transport mechanisms

The electrochemical profiles for K+, Na+, and Cl- ions in tissues of the lateral wall of the cochlea in the chinchilla were measured using an ion-selective microelectrode. Based upon the changes of the d.c. resting potential and ion composition, five distinct compartments were identified in the lateral wall. The first compartment, corresponding to the spiral ligament, showed an ionic composition similar to perilymph. The second, corresponding to the basal cell layer of the stria vascularis, showed a characteristic recording of the ion-sensitive barrel: a spike-like change of the ion concentration (K+: 100.1 +/- 16.8 mM, Na+: 33.9 +/- 20.2 mM, Cl-: 70.2 +/- 9.4 mM). The third compartment, corresponding to the extracellular space of the stria vascularis, showed a higher d.c. potential (60.4 +/- 9.5 mV) than that of the second region, with a low K+ concentration (22.1 +/- 14.9 mM) and a high Na+ (78.3 +/- 5.7 mV) than the fifth compartment, corresponding to the scala media (78.1 +/- 4.1 mV), and K+ and Na+ concentrations similar to those of endolymph, while the Cl- concentration in the fourth compartment (117.6 +/- 21.5 mM) was lower than that of endolymph (143.3 +/- 13.9 mM). A thermodynamic study of electrochemical potential gradients suggests the possibility that the Na-K pump and Na-K-2Cl cotransport exist at the basolateral membrane of the marginal cells.

Pathogenesis of Tympanosclerosis

In spite of the wealth of information on the clinical, histologic, and pathologic aspects of tympanosclerosis, the pathogenesis of tympanosclerosis is still unclear. In an attempt to understand the pathogenesis, 319 human temporal bones from 196 individuals with otitis media were studied. The extent and nature of tympanosclerosis and the characteristics of the otitis media associated with it were studied. Forty-five temporal bones from 35 individuals with otitis media were found to have tympanosclerosis, giving an incidence of 14.1%. It was seen most commonly in individuals over 40 years of age (86.7%). The male-to-female ratio was 1.6:1. The most common site of occurrence was the tympanic membrane (88.9%). Tympanosclerosis was seen more often in the anterior and posterior inferior quadrants of the tympanic membrane and that, too, in a central position. Tympanosclerosis was seen more commonly in temporal bones with irreversible inflammatory changes, and in this group, late plaques were more commonly seen than early or intermediate plaques. Audiometric charts failed to show any direct relationship between extent of tympanosclerosis and the severity of hearing loss. The only audiometric finding of any consequence was a mixed hearing loss in the presence of middle ear tympanosclerosis. (OTOLARYNGOL HEAD NECK SURG 1993;109:413–20.)

Hydrostatic pressure measurements of endolymph and perilymph in a guinea pig model of endolymphatic hydrops.

The primary histologic correlate of Menieres disease is endolymphatic hydrops. From this, many investigators have postulated the existence of endolymphatic hypertension, although there have been no measurements published to substantiate this concept. Seventy guinea pigs, surgically treated with right endolymphatic duct obstruction, were later assessed by use of a micro-electrode technique that measured their en-dolabyrinthine hydrostatic pressures. For 21 of these animals, the pressures of both scala tympani (Pst) and scala media (Psm) of both ears of each animal were successfully measured. Similar measurements were made in a control group of 25 guinea pigs that had not undergone any previous surgery. For normal ears-as well as those with hy-drops-pressure differences between perilymph and endolymph (Pst - Psm) varied around 0 >2.0 mm Hg. When only the right (obstructed) ears were considered, there appeared to be a slight, relative pressure elevation (p <0.05) in scala media during the first 7 days after endolymphatic duct obstruction-and in those ears with EP, less than 70 mV. The magnitude of this pressure difference that can be attributed to the state of endolymphatic hydrops-and not to natural variability-is calculated (within 95% confidence limits) to be less than 0.5 mm Hg.

Tympanostomy tubes and otic drops

Otic drops have been proposed as a form of prophylaxis against the otitis media which follows middle ear contamination by water in patients with tympanostomy tubes. The potential adverse effects of this form of therapy were studied in chinchillas with tympanostomy tubes; 31 chinchillas underwent bilateral tympanostomy tube insertion. Seven animals had a mixture of green dye and Cortisporinotic suspension placed in both external auditory canals 24 hours following the placement of tympanostomy tubes and were sacrificed 30 minutes later for gross examination; 3 of these animals had previous eustachian tube obstruction with Silastic sponge. Twenty‐one animals had Cortisporinotic suspension placed in the right external auditory canal on postoperative days 3, 4, 5, 6 and 7. No otic drops were placed in the left ear. Ten of these 20 animals had VIIIth nerve action potentials measured on postoperative day 17 and the other 11 animals had VIIIth nerve action potentials measured on postoperative day 42 followed by immediate sacrifice for histological examination and scanning electronmicroscopy. The remaining 3 animals had VIIIth nerve action potentials measured 21 days following tympanostomy tube insertion and served as electrophysiological controls.

The preparation of acetic acid for use in otic drops and its effect on endocochlear potential and pH in inner ear fluid

The ototoxicity of an otic drop preparation containing 2% acetic acid and 3% propylene glycol (VoSol, Denver Chemical Co., Humacao, PR) was investigated according to measurements of endocochlear potential (EP) and inner ear fluid pH. The application of this preparation to the round window membrane for 30 minutes caused a depression in EP from 80.5 +/- 2.5 mV (mean +/- SD; n = 6) to 11.7 +/- 7.7 mV, and lowered inner ear fluid pH from 7.55 +/- 0.09 to 5.06 +/- 0.19 (n = 6) in perilymph and from 7.52 +/- 0.07 to 5.88 +/- 0.63 (n = 6) in endolymph. Two percent acetic acid produced similar changes after 30 minutes: EP was reduced from 83.0 +/- 2.2 mV to 34.0 +/- 2.9 mV and endolymphatic pH from 7.49 +/- 0.04 to 6.83 +/- 0.21 (n = 4). However, the application of artificial perilymph of pH 4 titrated with HCl induced no significant changes in either EP or endolymphatic pH. We suggest that the mechanisms of ototoxicity in the otic drop preparation are Na+ and K+-ATPase inhibition, and that such inhibition is due to the intracellular acidification of strial cells resulting from the penetration of acetic acid across the cell membrane, and to the direct and synergistic actions of propylene glycol.

Effect of furosemide upon endolymph potassium concentration

Chinchillas were anesthetized with ketamine (40 mg/kg i.m.) and endocochlear potential (EP) and potassium concentration in endolymph (Ke+) were determined in control animals and in animals injected with various doses of furosemide (25, 50 or 100 mg/kg i.v.) by means of microelectrodes inserted into scala media. Control EP and Ke+ in the chinchilla were 81.3 +/- 3.8 mV and 158.5 +/- 3.2 mequiv./l, respectively. Following injection of furosemide, a dose-related fall in EP and Ke+ was observed. However, the EP declined much more rapidly than the Ke+, and recovered more quickly than the latter. The recovery of Ke+ tended to lag behind the EP recovery. The debate over whether potassium transport into endolymph and endocochlear potential generation are related or independent events is discussed in the light of recent literature and the present study.

Ototoxicity of propylene glycol in experimental animals

The ototoxicity of antibiotics given either systemically or topically has been recently recognized. However, the ototoxicity of topically applied alcohols and other solvents used as vehicles for drugs has not been well recognized. One of the most common solvents, propylene glycol, was chosen for this study, and this agent in various concentrations was instilled into the middle ear of guinea pigs and chinchillas for various periods of time. Its effect on the function of the cochlea was studied as well as the histopathologic changes in the temporal bones. Deterioration of the cochlear microphonics and the endocochlear direct current potential was found. A 10 per cent solution applied for six days caused a reduction in the cochlear microphonics. Fifty per cent or stronger solution always caused a reduction in the cochlear microphonics. The deterioration in the cochlear microphonics persisted one month. Dose related changes in the endocochlear potential were noted. Morphologic changes were severe and included granulation tissue in the middle ear and destruction and ossification of the auditory bulla and bony cochlea. Propylene glycol should not be used in the ear that has a perforation of the tympanic membrane.

Hypercholesterolemia and Auditory Dysfunction Experimental Studies

Rabbits were used for the long-term study of auditory function associated with experimental hypertension and hypercholesterolemia. Auditory dysfunction (threshold changes of sound evoked responses) was monitored with an electrode, chronically implanted into the contralateral inferior colliculus. Hypertension was created using the renal encapsulation technique. Auditory function in the hypertension trial demonstrated a dip at higher frequencies as well as improvement at lower frequencies. One gram of cholesterol fed daily for three months was capable of making rabbits atherosclerotic. Cholesterol-fed rabbits showed increasing auditory dysfunction over time at all frequencies. When experimental hypertension was combined with hypercholesterolemia, the auditory changes appeared additive. This work, although in preliminary stages, seems to provide experimental evidence that auditory dysfunction is associated with cholesterol diet.

Changes in EP and Inner Ear Ionic Concentrations in Experimental Endolymphatic Hydrops

Unilateral endolymphatic hydrops was created in guinea pigs by endolymphatic duct obstruction. Using microelectrodes, studies of endocochlear potential (EP) and inner ear ionic concentrations were performed. EP was significantly decreased whereas Na+, K+, and Cl- concentrations in both scala media and scala tympani were not significantly altered. The presence of a decreased EP after endolymphatic duct obstruction appears to be a reliable indicator for the presence of hydrops. This decrease in EP without ionic concentration changes suggests that it is the electrogenic portion of EP which is altered in hydrops.