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Influence of surgical plugging on horizontal semicircular canal mechanics and afferent response dynamics.

Mechanical occlusion of one or more of the semicircular canals is a surgical procedure performed clinically to treat certain vestibular disorders and used experimentally to assess individual contributions of separate canals and/or otoliths to vestibular neural pathways. The present experiments were designed to determine if semicircular canal afferent nerve modulation to angular head acceleration is blocked by occlusion of the endolymphatic duct, and if not, what mechanism(s) might account for a persistent afferent response. The perilymphatic space was opened to gain acute access to the horizontal canal (HC) in the oyster toadfish, Opsanus tau. Firing rate responses of HC afferents to sinusoidal whole-body rotation were recorded in the unoccluded control condition, during the process of duct occlusion, and in the plugged condition. The results show that complete occlusion of the duct did not block horizontal canal sensitivity; individual afferents often exhibited a robust firing rate modulation in response to whole-body rotation in the plugged condition. At high stimulus frequencies (about >8 Hz) the average sensitivity (afferent gain; spikes/s per degrees /s of head velocity) in the plugged condition was nearly equal to that observed for unoccluded controls in the same animals. At low stimulus frequencies (about <0.1 Hz), the average sensitivity in the plugged condition was attenuated by more than two orders of magnitude relative to unoccluded controls. The peak afferent firing rate for sinusoidal stimuli was phase advanced approximately 90 degrees in plugged canals relative to their control counterparts for stimulus frequencies approximately 0.1-2 Hz. Data indicate that afferents normally sensitive to angular velocity in the control condition became sensitive to angular acceleration in the plugged condition, whereas afferents sensitive to angular acceleration in the control condition became sensitive to the derivative of acceleration or angular jerk in the plugged condition. At higher frequencies (>8 Hz), the phase of afferents in the plugged condition became nearly equal, on average, to that observed in controls. A three-dimensional biomechanical model of the HC was developed to interpret the residual response in the plugged condition. Labyrinthine fluids were modeled as incompressible and Newtonian; the membranous duct, osseous canal and temporal bone were modeled as visco-elastic materials. The predicted attenuation and phase shift in cupular responses were in close agreement with the observed changes in afferent response dynamics after canal plugging. The model attributes the response of plugged canals to labyrinthine fluid pressure gradients that lead to membranous duct deformation, a spatial redistribution of labyrinthine fluids and cupular displacement. Validity of the model was established through its ability to predict: the relationship between plugged canal responses and unoccluded controls (present study), the relationship between afferent responses recorded during mechanical indentation of the membranous duct and physiological head rotation, the magnitude and phase of endolymphatic pressure generated during HC duct indentation, and previous model results for cupular gain and phase in the rigid-duct case. The same model was adjusted to conform to the morphology of the squirrel monkey and of the human to investigate the possible influence of canal plugging in primates. Membranous duct stiffness and perilymphatic cavity stiffness were identified as the most salient model parameters. Simulations indicate that canal plugging may be the most effective in relatively small species having small labyrinths, stiff round windows, and stiff bony perilymphatic enclosures.

Afferent Pathways↗

[Physiopathology of the inner ear and therapy of presbyacusis (author's transl)].

Many experimental investigations have shown that labyrinthine fluids play a basic role in the physiology of the inner ear. Modifications of perilymphatic fluids have been demonstrated in perceptive deafness (otosclerosis, Ménière's disease, tympanolabyrinthosclerosis). Vasoactive agents fail to markedly affect the exchange between labyrinthine fluids, so that perceptive syndromes are generally regarded as unresponsive to treatment. Several studies have shown the effectiveness of 10-methoxy-1,6-diemthyl-ergoline-8 beta-methanol-(5-bromonicotinate) (nicergoline, Sermion) in various conditions of the inner ear. In this investigation, 30 patients with presbyacusis were treated with 30 mg/day p.o. for 30 days. Speech audiometric curves were improved in 4 out of 18 cases of physiological presbyacusis and in 6 out of 12 cases of accelerated presbyacusis. These results are very interesting, since few effective therapies are available to treat these conditions.

Animals↗

Round window gentamicin absorption: an in vivo human model.

OBJECTIVE/HYPOTHESIS: Using a novel human labyrinthine sampling model, in vivo gentamicin absorption through the round window can be measured. STUDY DESIGN: A prospective study. METHODS: Gentamicin was delivered either transtympanically (preoperative) or through a facial recess approach (intraoperative). The lateral semicircular canal and vestibule were opened, and by means of a microsyringe, labyrinthine fluid was aspirated. A sample of serum was also drawn. In all patients cerebrospinal fluid was also drawn. The samples were analyzed using a standard chemistry analyzer. RESULTS: Intratympanic gentamicin diffused through the round window membrane and achieved concentrations in the labyrinthine fluid ranging from 0 to 16 mg/L. Intratympanic gentamicin was absorbed into the systemic circulation in 4 of 11 patients with serum levels ranging from 0.3 to 0.4 mg/L. No gentamicin was detected in the cerebrospinal fluid. CONCLUSIONS: Intratympanic gentamicin diffuses rapidly through the round window membrane and achieves significant levels in the inner ear. Thus, this new model can be used to assess round window permeability to clinically relevant medications such as steroids and ototopical antibiotics.

Adult↗

[Evaluation of the cochlear aqueduct patency: comparison of 2 noninvasive techniques].

Variations in cephalo-rachidian fluid pressure can be transmitted to the middle ear through the cochlear aqueduct (CA). This gives us a non-invasive manner to evaluate any changes in fluid pressure by measuring middle ear impedance (impedancemetry). The present study compared two indirect methods for measuring intracranial pressure: a) impedancemetry during evoked jugulo-tympanic reflex (JTR) and b) study of the tympanic membrane (TM) fine motility using a MMS-10 analyzer. The latter is a new procedure involving the indirect evaluation of the fluid pressure. In fact, when the CA is open the labyrinthine fluid pressure is transmitted to the oval window, the stapes platina and, finally, to the tympanic membrane where it can be measured with an MMS-10 unit. This equipment can measure nanoliter shifts in the TM. In particular, comparison between the clinostatic and orthostatic tympanic motility measurements enable one to establish whether the CA is patent or not. In the present study 15 subjects were examined using both a) impedancemetry during jugular compression and b) analysis of the TM shift using an MMS-10 unit. In 14 of the 15 cases there was good correlation between the data obtained using both methods: in all but one case it proved possible to record a JTR-induced variation in impedance whenever the MMS-10 indicated that the CA was open. The results suggest that, in clinical practice, the two methods can be used in parallel for non-invasive monitoring of variations in intracranial pressure in patients with neurological involvement. On the other hand, in the E.N.T. field these techniques could be used to study inner ear pathologies causing dynamic alterations of the endolabyrinth fluids (endolymphatic hydrops, labyrinthine fistula).

Acoustic Impedance Tests↗

Perilymph fistula: a cause of auditory, vestibular, neurological and psychiatric disorder.

It is suggested that damage by mild trauma, viruses or bone disease to the otic capsule or to the membranes between the cochlea and the middle ear is common, and involved in many syndromes of obscure etiology. The clinical perilymph fistula (PF) syndrome can consist of any combination of the following: tinnitus, deafness, phonophobia, vertigo, ataxia, otalgia, facial palsy, headache, diplopia, blackouts, psychological distress. The following testable hypotheses are proposed: otitis media is due to perilymph in the middle ear, with secondary changes resulting from infection or inflammation: otosclerosis results from a slow leak in the presence of enzymes promoting bone growth: Meniere's syndrome follows reduced perilymph support for the endolymphatic system: Bell's palsy results from a perilymph provoked oedema in the bony facial nerve canal: PFs may be responsible for progressive rubella deafness, and for some cases of migraine, epilepsy, anxiety neurosis and hysteria: psychiatric sequelae of the PF syndrome predominate in the post-concussional syndrome and infantile autism: organisms can pass from the throat into the spinal fluid, causing meningitis or encephalitis. The tinnitus and vertigo are caused by random labyrinthine fluid movements, the headache and diplopia by reduced spinal fluid pressure.

Deafness↗

Pressure transfer between intracranial and cochlear fluids in patients with Meniere's disease.

OBJECTIVES: To elucidate the pressure transfer between intracranial and labyrinthine fluids in patients with well-defined unilateral Meniere's disease. STUDY DESIGN: Eleven patients previously exposed to hypobaric pressure agreed to be investigated further with the tympanic membrane displacement (TMD) technique. TMD was used to indirectly analyze perilymph pressure changes as the result of changes in body position. METHODS: Repeated measurements for both the diseased and the healthy ears were made with the patients supine and then in a sitting position. The TMD parameters for the maximum inward displacement, the Vi, and the mean volume displacement, the Vm, were calculated and compared. RESULTS: The paired comparison showed statistically significant larger Vi values for both ears in the supine position. A similar tendency was observed for the Vm value. This difference of the Vi was significantly larger for the diseased ear compared with the currently healthy ear. The results were compared to the audiometric and electrocochleographic results previously obtained on the same patients when they were subjected to hypobaric pressure. Patients who experienced the largest differences in hearing level thresholds in the lower frequencies also showed the greatest differences in TMD values as the result of postural changes. CONCLUSIONS: Despite the limited number, the statistically supported results suggest a relation between the efficiency of the routes of pressure transfer and the observed effect of hypobaric exposure. The results also indicate that for the patients tested, the routes of communication are more effective in the diseased ear than in the healthy ear--a condition that may relate to the pathogeneses of Meniere's disease.

Adult↗

Morphometric comparison of endolymphatic and perilymphatic spaces in human temporal bones.

To measure the endolymphatic and perilymphatic spaces, we used human temporal bones (horizontal serial sections) under two selection criteria: absence of otological pathology, and absence of artifact in the membranous labyrinth (boundary between endolymphatic and perilymphatic spaces) maintaining an intact structural integrity. Under magnified projection, the area of scala tympani, scala vestibuli, scala media, vestibular endolymphatic space, and vestibular perilymphatic space were measured separately, using a microcomputer digitizing tablet. Three repeated measurements were obtained and averaged. The mean total labyrinthine fluid space was 204.5 mm3; the mean total endolymphatic space was 38.1 mm3 and mean total perilymphatic space 166.4 mm3. The mean total vestibular fluid space was 120.9 mm3 and mean total cochlear fluid space 83.6 mm3. In the vestibule, the perilymphatic space occupied 74.8%, and the endolymphatic space, 25.2%, whereas 90.8% of the cochlear fluid space was occupied by perilymph.

Adult↗

Late dosing with ethacrynic acid can reduce gentamicin concentration in perilymph and protect cochlear hair cells.

A key factor in the well-known interaction between ethacrynic acid (EA) and aminoglycoside antibiotics (AABs) is disruption of the blood-labyrinth barrier (BLB), leading to rapid entry of EA and AABs into the cochlear fluids. The idea that the blood-labyrinthine fluid concentration gradient might be utilized in a protective manner was tested in the current experiment. We hypothesized that administering EA when gentamicin (GM) levels are higher in the cochlea than in the blood might actually reduce cochlear damage by permitting efflux of GM from the cochlear fluids into the bloodstream, down a concentration gradient and across a temporarily disrupted BLB. Guinea pigs received 1, 11, 14 or 20 injections of GM (125 mg/kg i.m.). Approximately half of the animals also received a single injection of EA (40 mg/kg i.v.) either concurrently or 12-18 h after the last GM injection. Concurrent injection of EA significantly increased GM concentration in serum and perilymph at all time points sampled (2.5, 5-8, and 12 h post injection). Compared to animals that received GM only, animals that received a delayed injection of EA had a significantly lower GM concentration in perilymph, lower thresholds of the compound action potential, and less outer hair cell loss. Collectively, the evidence suggests that EA can reduce GM ototoxicity if it is administered 12-18 h after GM, but the mechanism remains to be elucidated. The results may have implications for the clinical management of aminoglycoside ototoxicity in humans, as well as for understanding the mechanisms underlying AAB/EA interactions.

Action Potentials↗

[Morphological features of experimental transient endolymphatic hydrops].

This paper describes a method for simulating transient endolymphatic hydrops based on the generation of vasomotor disorders in the labyrinthine artery area. The method is based on a deep short-term chloroethyl freezing of the lateral surface of the animal surface in the projection of the spinal artery. In histological terms, hydrops is characterized by two factors: vascular lesions (hyperemia of the vascular stripe, venous congestion) and changes in physico-chemical parameters of labyrinthine fluids (edema of cell elements of the labyrinth, membrane deformation, precipitation of the granular-reticular residue in the endo- and perilymphatic spaces). This method can be used to study the origin of endolymphatic hydrops during Ménière's disease, to develop new approaches and to give a pathogenetic substantiation of existing approaches to the treatment of Ménière's disease.

Animals↗

Labyrinthine barriers and cochlear homeostasis.

The blood-labyrinth barrier is a concept used to explain the stability of composition of the labyrinthine fluids in spite of systemic alterations in blood composition. This blood-labyrinth barrier concept was tested by injecting various test substances into the systemic circulation of experimental animals and recovering these compounds in perilymph. The concentration of each test substance in perilymph lagged behind that of serum, and the transport of a series of test substances was found to be inversely related to the molecular weight and diameter. Among the osmotic agents injected, glycerol and urea penetrated into perilymph to a considerable degree, however, mannitol did not enter perilymph in any significant amount. This may explain the clinical differences noted with these agents in testing for Meniere's disease. Furosemide, an ototoxic diuretic, was found to penetrate into perilymph after intravenous injection into chinchillas. The concentration of furosemide, measured by high pressure liquid chromatography, was fairly constant at the time of full recovery of endocochlear potential after doses of 50-200 mg/kg. The principle of correlating drug concentration in serum and in inner ear fluids with pathophysiologic effect may provide a prediction of threshold concentration of ototoxic effect by measurement of serum concentration of the drug. More extensive studies are necessary to clarify the role of the blood-labyrinth barrier in the regulatory mechanisms which maintain the homeostasis in the inner ear and the pathology which may follow when this homeostasis is disrupted.

Biological Transport↗

Transmission of cerebrospinal fluid pressure via the cochlear aqueduct and endolymphatic sac.

The concept of perilymphatic and endolymphatic pressure balance is generally linked to the theory that the endolymphatic sac transmits cerebrospinal fluid (CSF) pressure changes to the endolymph to equalize CSF pressure changes transmitted to the perilymph via the cochlear aqueduct. This theory, and the significance of other mechanisms of CSF pressure influence on the labyrinth, were evaluated experimentally. Continuous measurements of perilymphatic, CSF, venous, and arterial pressures were performed on cats with the cochlear aqueduct patent or obstructed and the inferior cochlear vein intact or occluded. Intracranial pressure changes were induced by subarachnoid infusion of artificial CSF in live and dead animals. With the cochlear aqueduct patent, CSF pressure changes were transmitted to the perilymph without any significant dampening or time lag. With the cochlear aqueduct obstructed, CSF pressure changes induced significantly lower and delayed changes in perilymphatic pressure. Similar results were obtained whether the animals were alive or dead and the cochlear vein intact or blocked. This indicated a passive mechanism not induced by changes in labyrinthine fluid production or blood flow. Long-standing, stable elevation of CSF pressure with the cochlear aqueduct blocked induced a slowly increasing perilymphatic pressure, always stabilizing at a pressure rise significantly less than that of CSF. The results do not suggest any major pressure transfer via perineural or perivascular routes. The endolymphatic sac is postulated to mediate a reduced and delayed transfer of increased intracranial pressure to the labyrinth.

Animals↗

[Oscillometry on various stape protheses. Experimental examination of human temporal bone preparations].

In human temporal bone specimens the vibrations of the labyrinthine fluid were measured by a piezoelectric system after application of various techniques of otosclerosis surgery. Compared with the amplitude in the case of a normal stapes, the surgical techniques according to Zangemeister, Shea and Schuknect resulted in considerable transmission losses in the high frequency range, while transmission of low frequencies to the inner ear was almost equivalent to normal transmission via the stapes. For frequencies of more than 3,000 Hertz the damping influence of the fibrous tissue implanted into the oval window was verified. The results of surgery according to Zangemeister, Shea and Schuknechtdid not differ significantly in the low and medium frequency range. Only a Robinson prosthesis implanted like a Teflon piston caused an impairment of transmission, while the method of fitting this prosthesis onto fibrous tissue was equilvalent to the other techniques.

Ear, Middle↗

Experiments on fluid movements through the labyrinthine membranous walls.

Methods were selected and tested for studying the flux of water through the labyrinthine walls. Mannitol which does not pass through the walls was used in isotonic concentration in the endolymphatic space, and various concentrations of mannitol solutions in the perilymph space created a concentration gradient which resulted in a flux of water through the membranous wall. This is a first step in investigating the flux of solutes and solvent through these walls of the labyrinth as a basis for studying substances which chronically increase the colloid osmotic pressure due to their difficulty in passing the walls.

Animals↗

Pressure transfer between the perilymph and the cerebrospinal fluid compartments in cats.

This is a review of our studies of the labyrinthine fluid pressure in cats subjected to pressure changes in the middle ear (implosive routes) and the cerebrospinal fluid compartment (explosive routes) as well as to changes in vascular and ambient pressures. The perilymph, cerebrospinal fluid (CSF), middle ear, venous and arterial pressures were measured with the cochlear aqueduct (CA) patent as well as surgically blocked. Experiments on explosive pressure changes revealed that the perilymph pressure was regulated by the CSF in case of CA patency. The CSF influence was dominant enough to obscure any direct effect on the labyrinth from other sources. With the CA obstructed the CSF influence on the labyrinth was apparently mainly via the endolymphatic sac and duct although limited and much delayed. Systemic arterial pressure changes had a pronounced influence on the perilymph pressure, but this effect was revealed only when the CSF influence was reduced by CA obstruction. Experiments on implosive and ambient pressure changes suggested that there was no fundamental difference in the perilymph response to equivalent levels of implosive versus hypobaric pressure. Three factors determined the effect of implosive and hypobaric pressure: the patency of the CA, the rate of the pressure change, and the eustachian tube function.

Air Pressure↗

[Changes in the blood-labyrinth barrier. Assessments by magnetic resonance].

PURPOSE: Recent progress in magnetic resonance imaging (MRI), with contrast-enhanced and steady-state sequences, allows fine depiction of labyrinth abnormalities related to neoplastic, inflammatory, ischemic, degenerative or traumatic disorders. We examined 488 patients with sensorineural hearing loss, vertigo or dizziness, but normal CT findings, to evaluate MR capabilities in showing labyrinth conditions. MATERIAL AND METHODS: January 1994 to May 1998, four hundred and eighty-eight patients with labyrinthine symptoms were submitted to CT. Sixty-eight of them, with normal CT findings, were also examined with MRI, which was performed using quadrature head or surface coils and a single dose (0.1 mmol/kg) Gd-DTPA administration. Conventional T1 and T2 high resolution SE images were acquired. The labyrinth was studied of 52 patients with normal CT findings and no abnormalities in the cerebello-pontine angle or internal auditory canal. RESULTS: Fourteen of 52 patients (27%) exhibited labyrinth enhancement from tumor (5%), hemorrhage (3%), infection (15%), surgical (2%) or radiosurgical (2%) procedures. GRASS sequences allowed differentiation of mass lesions (e.g., tumors, clots) from other conditions. CONCLUSION: Generally the labyrinth exhibits no contrast enhancement even after a triple Gd-DTPA dose. In inflammatory conditions, enhancement is not always diffuse, as expected, but may be focal. Spontaneous hemorrhages can account for labyrinth enhancement. In neoplastic conditions, enhancement may persist for as many as 6 months, and a mass effect against labyrinthine fluids may appear on GRASS images. Although there are no reports on labyrinthine degeneration after radiation therapy, one of our patients submitted to irradiation 7 years previously, had focal bilateral cochlear enhancement, which suggested a correlation with previous treatment.

Capillary Permeability↗

Traces of perilymph detected in epipharyngeal fluid: perilymphatic fistula as a cause of sudden hearing loss diagnosed with beta-trace protein (prostaglandin D synthase) immunoelectrophoresis.

The incidence of perilymphatic fistula as cause of sudden hearing loss is not known. We present a case with sudden unilateral hearing loss associated with a positive beta-trace protein test of an epipharyngeal fluid sample. The patient presented with sudden sensorineural hearing loss on the right side. A stapedotomy had been performed nine months previously due to otosclerosis. Intravenous therapy for the treatment of sudden hearing loss was unsuccessful. At the time of sudden hearing loss, epipharyngeal fluid was collected using a Raucocel sinus pack. Investigation using rocket immunoelectrophoresis showed the presence of beta-trace protein. Upon repeating tympanoscopy there was no obvious labyrinthine fluid egress, but the oval window was sealed with fibrin sponge and fibrin glue. The patient's hearing improved over a period of five months.

Adult↗

Fluorescein use in the detection of perilymphatic fistula: a study in cats.

A stained or colored perilymph would be a valuable tool to otologists for the detection of a perilymph fistula. We studied the effect of intravenously injected fluorescein on the inner ear in seven cats. Still and video photography was used to clearly document our findings. Intravenously injected fluorescein appeared within the soft tissue in less than 1 minute and stayed there for at least 3 1/2 hours. Fluorescence around the round window niche resulted from soft tissue (mucosal) fluorescence and extravasation of interstitial fluid (transudate). No fluorescence of perilymph was detected. Because of this, we do not believe intravenously injected fluorescein is useful in the detection of perilymph fistula. Intrathecal injection caused quick and intense staining of labyrinthine fluid.

Animals↗

The presence and localization of receptors for atrial natriuretic peptide in the inner ear of the guinea pig.

Atrial natriuretic peptide (ANP) is a cardiac hormone known to mediate increased capillary permeability, vasodilation, and natriuresis. Since specific receptors for ANP exist in both the eye and brain, possibly playing a role in ocular and cerebrospinal fluid regulation, we postulated that ANP might also be involved in inner ear fluid dynamics. Autoradiography was used to evaluate whether and where ANP receptors are present in the inner ear. Frozen sections of the cochlea and vestibular organ from guinea pigs (n = 18) were incubated in either 125J-ANP alone or together with an excess of unlabeled ANP (as control). ANP receptors were demonstrated in the stria vascularis of the cochlea and in the secretory epithelium of the ampulla and the utriculus, but not in the region of the sensory cells. These results indicate that (1) specific ANP receptors are present in the inner ear, and (2) their local distribution is congruent with those parts thought to regulate labyrinthine fluid composition and volume. We speculate that ANP contributes to the homeostasis of the inner ear fluids and may even play a role in the pathophysiology of Menière's disease.

Animals↗