Pathophysiology of Meniere's disease and its subvarieties.
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Animals↗
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Utricular and saccular volumetry in human temporal bones.
Using serially sectioned human temporal bones, endolymphatic volumes of utriculus and sacculus were measured with the aid of a computer. The mean of the utricular volume was 8.187 mm3, and the saccular volume, 2.096 mm3. The former was 3.9 X the latter. The surface area of the macula utriculi was 3.271 mm2, and the macula sacculi was 2.188 mm2. The former was 1.5 X the latter. The study using pathologic temporal bones (Meniere's disease, otosclerosis, and otitis media chronica) showed that the utricular volume could indeed increase, and the saccular membrane was found to be more fragile than the utricular membrane in those diseased conditions.
Child, Preschool↗
Perilymph oxygenation in sudden and progressive sensorineural hearing loss.
The perilymphatic oxygen tension of the vestibular perilymph of 34 patients with different inner ear losses were measured with the polarographic method before and after inhalation with carbogen. Two patterns of disturbed perilymphatic oxygenation were observed: 1) Characterized by low initial values of perilymphatic oxygenation and normal response to carbogen inhalation was present in sudden deafness and sudden cochleovestibular loss of inner ear function. 2) Characterized by normal initial values of perilymphatic oxygenation and a low response to carbogen, was found in presence of a slowly progressive sensorineural hearing loss. The significance of the obtained results in regard to the possible vascular pathology of the inner ear is discussed.
Adult↗
Effects of pure tone on endocochlear potential and potassium ion concentration in the guinea pig cochlea.
Preliminary results presented here indicate a simultaneous decrease in endocochlear potential (EP) and in endolymphatic potassium ion concentration (K+e) under noise exposure. Maximum changes were observed after 20 min and 30 min of sound stimulation, respectively for EP and Ke+. EP recovery was faster than that of K+e. Noise-induced K+e alterations varied with the pure-tone frequency, and the locus along the basilar membrane where the measurements were performed. This supports the hypothesis that the noise has a tonotopic effect correlate with the shape of the travelling wave. Results obtained with ethacrynic acid, administered at the end of the recovery period which followed the noise exposure, indicate that the sound stimulation parameters which were used did not irreversibly alter the ionic transport in the cochlea.
Acoustic Stimulation↗
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.
Animals↗
Effect of high perilymphatic potassium on brainstem evoked response audiometric thresholds.
The perilymphatic space of the cat cochlea was perfused with a solution containing a high potassium ion concentration. The auditory response threshold was monitored with brainstem evoked response audiometry. In the majority of animals the initial perfusion produced a reversible decline in response threshold. With repeat perfusions, there was a variable degree of non-reversible response decline leading ultimately to a total loss of the auditory response.
Animals↗
Histopathological study of the cochlea with altered perilymph metabolism.
In 41 guinea pigs an experiment was conducted to determine the effect of kanamycin on ears with or without blockage of the cochlear aqueduct. In 24 animals the cochlear aqueduct was blocked on one side, and after 1 to 21 days, kanamycin (300 mg/kg) was given daily and subcutaneously until the pinna reflex began to decrease. The remaining animals were used for controls: exposure of and trauma to the aperture of the cochlear aqueduct and kanamycin administration (8), blockage of the cochlear aqueduct only (3 plus 17 previous cases), and kanamycin administration to normal animals (6). The survival time of all these animals was four months. The results showed that ears with blockage of the cochlear aqueduct and kanamycin administration consistently demonstrated a more severe and extensive atrophy of the cochlear sensory cells. The lesions occurred primarily at the basal end and spread toward the apical turn, although the lesions in some specimens jumped from the basal to apical turn. The outer hair cells were more extensively affected than the inner hair cells. Proteinaceous precipitates were often found to be slightly greater in the perilymph of cochleae with blocked cochlear aqueducts. From these observations, it is concluded that the decrease in patency of the cochlear aqueduct will impair perilymph metabolism, causing the cochlear sensory cells at the basal turn to become more vulnerable to noxious substances.
Animals↗
Peptides of the otosclerotic perilymph examined by analytical isotachophoresis.
Perilymphs of normal and otosclerotic origin were separated chromatographically on a Sephadex G-25 microcolumn. Peptide composition of the perilymphs was compared by capillary analytical isotachophoresis in the molecular mass range 0.3-5 kD. Otosclerotic perilymph samples contain a heterogeneous, UV-absorbing peptide subfraction which is not detected in the normal perilymph. Normal and otosclerotic perilymph, furthermore, contain four common subfractions detected in twice the normal concentration in the otosclerotic perilymph. These ITP subfractions are degraded during acid hydrolysis (6 M HCI). On the contrary, otosclerosis is a deficient state compared with the normal, as the number of peptides or oligoglycopeptides is twice as high in normal as in otosclerotic perilymph, beside the otosclerosis specific peptides.
Electrophoresis↗
Saccular and cochlear endolymphatic potentials in experimentally induced endolymphatic hydrops of guinea pigs.
Saccular and cochlear endolymphatic potentials (SEP and CEP) were recorded in 33 normal animals. We confirmed that SEP is not produced in the saccule per se, but is a potential leak from the cochlea. CEP was reduced to one-tenth of the original value when it reached the saccule. Endolymphatic hydrops was provoked in 32 animals, and CEP and SEP were successfully recorded in 29 and 20 cases, respectively. The measurements were performed in the 2nd, 4th and 12th postoperative week. Both CEP and SEP decreased in magnitude as time elapsed after the surgery. This reduction is attributed to the strial dysfunction. In advanced hydrops, CEP transmission to the saccule is greatly inhibited. It is concluded that the saccular dysfunction can occur in the hydropic ear.
Animals↗
Calcium transport in the endolymphatic space of cochlea and vestibular organ.
Ca++ concentrations and d.c. potential within the endolymphatic space of the cochlear duct and the semicircular canal following acute anoxia or ethacrynic acid intoxication (100 mg/kg i.v.) were measured by means of double-barrelled microelectrodes. Ionic calcium content and d.c. potential were found to change in a roughly biphasic fashion after either intervention. The maximal increase in Ca++ concentration coincided with the decline in the d.c. potential, which after a rapid decline finally reached and maintained negative voltages. This phenomenon was more pronounced in the cochlear part than in the semicircular canal. A model of calcium homeostasis is proposed in an attempt to reconcile the data presented with earlier evidence.
Animals↗
Effects of experimental renal insufficiency on the osmotic pressure and the biochemical composition of perilymph.
The biochemical effects of experimental renal insufficiency produced by bilateral nephrectomy on perilymph were studied. Rats were used for the experiments; measurements were carried out at various intervals after nephrectomy. Statistically significant changes in perilymph (osmolality, Na, K, Cl, and urea), and serum (osmolality, urea and creatinine) were found. These findings represent a marked labyrinth alteration, and may partly explain the pathophysiology of labyrinthine disturbances in chronic renal disease.
Animals↗
Effect of high perilymphatic potassium concentration on the guinea pig vestibular sensory epithelium.
The 'rupture theory' has been proposed to explain the vertiginous attack of Meniere's disease, and the high perilymphatic potassium concentration was thought to be the most important factor in this theory. In this investigation, potassium ion was introduced through the round window into the perilymphatic space in guinea pigs by means of iontophoresis, to investigate the effect of high perilymphatic potassium concentrations on the vestibular sensory epithelium, histochemically. Following the iontophoretic procedure, spontaneous nystagmus was observed, directed toward the iontophoretic side (irritative nystagmus) for the first 10 min, and then toward the unaffected side (paralytic nystagmus) for 24 h. Both these nystagmus types were quite reversible and left no morphological change in sensory cells. However, histochemical analysis revealed an increased ATPase activity during the irritative nystagmus and decreased ATPase activity during the paralytic nystagmus in the synaptic area between the hair cells and the nerve endings of the vestibular sensory epithelium on the iontophoretic side. Judging by these results, high perilymphatic potassium concentration is assumed to affect the synaptic area of the sensory epithelium, leading to reversible nystagmus.
Animals↗
The effect of vitamin D deficiency on the cochlear potentials and the perilymphatic ionized calcium concentration of rats.
Sensorineural hearing loss has been frequently reported in patients with renal failure but its etiology has not yet been established. Disturbance of Ca metabolism is present in renal failure and seems to cause hearing loss. The purpose of the present study was to determine whether the disturbance of Ca metabolism has any effect on cochlear function. The cochlear potentials were measured in 19 rats fed with a vitamin D deficient diet. The pathological findings showed prolongation of N1 latency with unchanged N1 amplitude and pseudothreshold, depression of CM amplitude and elevation of the CM pseudothreshold. The latencies of narrow-band APs were prolonged in the entire cochlear partition. Ca2+ concentration in perilymph was 3.2 X 10(-4) M (n = 4) in vitamin D deficient rats and 7.4 X 10(-4) M (n = 4) in the controls. These findings were milder than those obtained in surgically induced renal failure. It was concluded that although vitamin D deficiency is one cause of hearing loss in renal failure, other major factors must be involved. The authors postulate that hearing loss in vitamin D deficiency is mainly attributable to the depression of the Ca2+ concentration in perilymph.
Action Potentials↗
The influence of semicircular canal morphology on endolymph flow dynamics. An anatomically descriptive mathematical model.
The classic Steinhausen/Groen mathematical description of endolymph flow in a toroidal semicircular canal is extended to the case where the size, shape, and curvature of the canal lumen change continuously through the duct, utricle, and ampulla. The resulting second-order differential equation has three coefficients, unlike the equation of a torsion pendulum, which has only two. The salient anatomical parameters which determine endolymph motion are: the length of the central streamline occupying the center of the canal lumen; the area enclosed by this streamline as projected into the plane of rotation; the average inverse cross-sectional area of the lumen (taken around the central streamline); and the average inverse squared cross-sectional area, weighted by a local wall shape factor. These parameters are evaluated and the average displacement of the face of the cupula is estimated for the human, guinea pig, and rat, based on new anatomical data presented in companion papers. The model predicts that the dynamic range of human average cupula motion lies between 520 A and 10 microns.
Animals↗
The effect of the cationic composition in perilymph upon the N1 latency of the guinea pig.
Although a suitable cationic composition in perilymph is known to be essential for the generation of N1, the effect of the cationic change upon the N1 latency has never been investigated in detail. The scala tympani was perfused with an artificial perilymph with a high K+, low Na+ or low Ca2+ content, with simultaneous measurement by an ion-selective microelectrode to observe its effect upon the N1 latency. An excess of K+, a depletion of Na+ and a depletion of Ca2+ in perilymph individually suppressed the N1 amplitude and elevated the N1 threshold. The N1 latency was not prolonged in the high K+ group but the significant prolongation was observed in the other two groups.
Animals↗
The low temperature vacuum embedding technique for X-ray microanalysis of the developing inner ear.
The method of low-temperature embedding in vacuo using methacrylate resins, was tested for X-ray microanalysis of the embryonic inner ear of the CBA/CBA mouse. Fetal inner ears were examined on gestational days 16 and 18. The technique was evaluated in comparison with earlier used preparation techniques for X-ray microanalysis. With plastic embedding, an improvement of the morphological resolution was achieved, which allows reliable structural identification on the subcellular level. Furthermore, the possibility of orientating of the specimen prior to sectioning provides a better controlled and less time-consuming sectioning.
Animals↗
Cathepsin D activity in otosclerotic bone and perilymph.
Otosclerotic bone and perilymph samples obtained during stapedectomy operations from patients suffering from pure conductive hearing loss of at least 40 dBs air-bone gap at 500 Hz. Control perilymph samples derived from patients suffering from round window membrane rupture or Meniere's disease. Enzyme activities were determined using a synthetic fluorogenic substrate by fluorescence spectrophotometry. No significant differences have been found between the protein content of otosclerotic and normal or non-otosclerotic perilymph samples. Cathepsin D activity was significantly higher (p less than 0.001) in the otosclerotic perilymph samples. Otosclerotic stapes footplate contained more activity than normal meatal cortical bone as well, though the difference was not significant. Biological significance of the elevated Cathepsin D activity must be considered.
Cathepsin D↗
Effects of prostaglandins on perilymphatic oxygenation. Enhancement of cochlear autoregulation by prostacyclin.
Effects of prostaglandin E1, prostacyclin, a prostacyclin analogue (OP-2507), and an inhibitor of thromboxane A2 synthetase (OKY-046) on the perilymphatic oxygen tension were measured in the feline tympanic perilymph under various respiratory conditions and blood pressure ranges. Factors influencing the capacity of the autoregulative properties of the inner ear vessels to accommodate changes in systemic blood pressure were also examined. Intravenous administration of prostacyclin, OP-2507, and OKY-046 prevented a decrease in perilymphatic oxygen tension when the systemic blood pressure decreased. Even a negative correlation of the differential coefficients between the perilymphatic oxygen tension and the systemic blood pressure was noticed during the administration of prostacyclin. Thus, prostacyclin enhanced the autoregulative property of the inner ear vessels. Furthermore, correlation studies between perilymphatic oxygen tension and cochlear blood flow demonstrated a partial dissociation, indicating the presence of autoregulation in the mean systemic blood pressure range under 80 mmHg.
Alprostadil↗