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Experimental study of sacculotomy in endolymphatic hydrops.

Thirty-nine guinea pigs were used for four groups of experiments: 1. sacculotomy only, 2. sacculotomy and simultaneous obliteration of the endolymphatic duct, 3. sacculotomy followed by obliteration of the endolymphatic duct, and 4. obliteration of the endolymphatic duct followed by sacculotomy. Sacculotomy alone caused only minimal cochlear pathology, whereas sacculotomy on hydropic ears produced severe atrophy of the organ of Corti and cochlear neurons as well as connective cells of the limbus. There was histological evidence that Reissner's membrane in hydropic ears was ruptured by the sacculotomy procedure. The primary cause for the severe atrophic changes is thought to be the toxic effect of intermixing perilymph with a large volume of endolymph. The surgically induced saccular tears appeared to be healed in all ears, and the procedure had no significant effect on the course of endolymphatic hydrops. Although two out of eleven specimens in which sacculotomy was performed on hydropic ears showed tears and collapse of Reissner's membrane, since others with similar tears showed extensive hydrops, the possibility of artifact could not be ruled out. In one specimen with simultaneous sacculotomy and obliteration of the duct, persisting fistulae were noted at the sites of accidental fracture of the osseous spiral lamina; this ear is the only one which failed to develop hydrops following obliteration of the duct. The results of this experiment, namely sacculotomy on hydropic guinea pig ears, suggest that sacculotomy is not a rational procedure for the control of endolymphatic hydrops in Ménière's disease for the following reasons: 1. surgically induced tears in the saccular wall are followed by rapid healing and 2. intermixing of perilymph and a large volume of endolymph causes toxic atrophy of the limbus, organ of Corti and cochlear neurons.

Animals↗

Time course of anoxia-induced K+ concentration changes in the cochlea measured with K+ specific microelectrodes.

The endocochlear potential (EP), potassium concentration in the endolymph (Ke+) and in the perilymph (Kp+) were measured in guinea-pigs during anoxia of different duration. Specific K+ double-barrel microelectrodes with liquid ion exchanger were used. The resting K+ concentration in the endolymph was 146.8 +/- 9.2 mM and in the perilymph 3.2 +/- 0.5 mM. The following time course of events was observed in the cochlea during anoxia: 40-50 s after the arrest of ventilation the K+ concentration decreased by 0.1-0.2 mM in the scala vestibuli, which was time related to a rapid fall of EP to negative values. Perilymphatic K+ started to increase in both scalae with a latency of 2-2.5 min, reaching a concentration of about 14 mM 60 min after the arrest of ventilation. The endolymphatic K+ began to decrease after a latency of 2.5-3 min, and 60 min after the arrest of ventilation an 80% concentration (average 112 mM K+) was reached as compared to the initial value. From the comparison of K+ concentration changes with the experimental values of the negative EP, it may be assumed that the negative EP is mainly generated by the K+ gradient between the perilymph and endolymph.

Animals↗

Some features of the medium surrounding the mechano- and electroreceptors of the acousticolateral system of the ray Raja clavata.

The degree of binding of K ions has been investigated and the contents of free Ca ions and of glycosaminoglycans have been determined in the medium surrounding the mechano- and electroreceptors of the acousticolateral system of the ray Raja clavata; in addition, electrical phenomena in solutions of K hyaluronate in solutions of the media investigated have been studied. A comparison of the results of electrometric and chemical analysis has shown that the proportions of bound K ions as percentages of the total amounts of these ions are 36.4 in the endolymphatic jelly, 39.6 in the ampullar jelly, and 21.9 in the liquid of the lateral canals. The amount of Ca ions in the media investigated is 3.6-4.4 meq/liter and is close to the concentration of these ions in sea water--3.4 meq/liter. In the endolymphatic jelly the amount of glycosaminoglycans is 0.30+/-0.022% of the wet weight, in the liquid of the lateral canals 0.21+/-0.026%, and in the jelly of the ampullae of Lorenzini 2.79+/-0.28%. Some characteristics of the "displacement potentials" of solutions of K hyaluronate and solutions of the jelly of the ampullae of Lorenzini have been determined, and some hypotheses have been put forward on the possible role of these potentials in the activity of the ampullar formations of the systems of organs of the lateral line.

Animals↗

[Kinetics of resorption in the cochlear perilymph after charging with radionuclides (author's transl)].

The perilymphatic space of the guinea pig's cochlea is filled within 1 to 3 min with an isotonic Ringer solution labelled with a radionuclide. The cochlea is neatly sealed immediately afterwards, thus causing only a minimal disturbance in the inner ear. The animal's cochlea is brought into the strict focus of a small detector as quickly as possible, the decay of activity is continuously controlled for 2 to 10 hrs. The radionuclides used are Cl36, Na22, and Tc99m. The decay of activity of the cochlea is strongly believed to accord to a simple exponential law; half lives range from about one to about three hours. Cl36 and Tc99m were used for the first time in studying cochlear kinetics.

Animals↗

Modulation of activity in starling cochlear ganglion units by middle-ear muscle contractions, perilymph movements and lagena stimuli.

In the present study three groups of cochlear ganglion neurons were detected which differed in respect to their tone-evoked and spontaneous activity: auditory units which showed an irregular spontaneous discharge, non-auditory neurones with regular activity and such with an irregular spontaneous discharge pattern. Electrically-elicited contractions of the middle-ear muscle influenced the tone-evoked and/or the spontaneous activity of the auditory and the non-auditory neurones with irregular spontaneous discharge but not, however, the regularly firing units. Similar results were obtained with imposed perilymph movements in the cochlea (evoked via the vestibular system. Fractions of all three groups of cochlear ganglion neurones were responsive to direct deformations of the membraneous lagena. Several (auditory and non-auditory) units with irregular discharge were excited during a basilar membrane displacement towards scala vestibuli whereas a basilar membrane motion towards scala tympani resulted in a decrease of the discharge rate. A few units showed a different reaction. The results provide evidence that the neurones with periodic spontaneous discharge innervate the lagena and that this sense organ has no auditory significance in birds. The peripheral origin of the 'non-auditory' neurones with irregular spontaneous activity remains undecided and might be the macula lagenae or the apical portion of the basilar papilla.

Action Potentials↗

The pharmacokinetics of azlocillin in the perilymph of guinea pigs and otitis media.

The results of studies on the pharmacokinetics of azlocillin in the perilymph of the guinea pig following the intramuscular administration of 200 mg per kg body weight are shown graphically. Similar to mezlocillin and the aminoglycoside antibiotics, this new acylureido penicillin is retained in the inner ear. The results of our studies, together with the data on the in vitro and in vivo activity of azlocillin and gentamicin and the applicable dosage for clinical purposes, indicate that the azlocillin levels in the perilymph are considerably more effective against Pseudomonas aeruginosa and many times more effective against the other microorganisms usually involved in acute otitis media than those of the aminoglycosides.

Animals↗

Endolymphatic leakage in case of acute loss of cochlear microphonics.

Rapid loss of cochlear microphonics in guinea-pigs previously exposed to high-energy impulse noise was shown to be related to the breakdown of the endolymphatic boundary. The cochlear duct was rendered leaky by deterioration of the reticular membrane, and damage of sensory and supporting cells.

Animals↗

The effect of clofilium, a K-channel blocker, on the electrogenic K secretion and the sensory discharge at the frog semicircular canal.

Potassium transport by dark cells produces marked K-concentration differences between endo- and perilymphatic fluids in labyrinthine organs and generates the transepithelial potential. The ensuing electrochemical potential for K sustains the transduction current which regulates activity at the cytoneural junction. Clofilium, a compound which is known to block cardiac K channels and to decrease the endocochlear potential, was applied to the endolymphatic side of the isolated frog semicircular canal. The drug abolished the transepithelial potential and increased K outflux from the lumen to the dark cells (or the basolateral perilymph) with no apparent interference with active K secretion. When applied to the perilymphatic side in the intact labyrinth, clofilium reduced the rate of occurrence of miniature excitatory postsynaptic potentials (mEPSPs), both at rest and in response to mechanical stimulation (sinusoidal rotation at 0.1 Hz, 12.5 deg/s2 peak acceleration). This effect may be related to a reduced K-electrochemical unbalance and a decreased transduction current. The drug consistently reduced mEPSP size, although amplitude distributions remained log-normal and time intervals between successive mEPSPs remained exponentially distributed; this suggests a direct effect of clofilium on the postsynaptic membrane, in addition to any possible presynaptic effects. Spike discharge by the afferent fibre was almost completely abolished at rest and responses to mechanical stimulation were reduced by 85-90%. These effects cannot be accounted for by the mild reduction of mEPSP rates and confirm a direct action of clofilium on the afferent postsynaptic terminal.

Animals↗

Calcium gradients in inner ear endolymph.

Recent studies suggest that endolymphatic hydrops resulting from the ablation of the endolymphatic duct and sac in guinea pigs may be caused by a disturbance of endolymph calcium homeostasis. A similar disturbance of calcium homeostasis could represent the underlying cause of Ménière's disease. In this study, we mapped the calcium concentrations and electrical potentials throughout the endolymphatic system in normal guinea pigs. Large concentration differences exist between different compartments, including a more than twofold increase along the length of the cochlea. The electrochemical potential for calcium (the force driving passive longitudinal calcium movement) was calculated for all the endolymphatic compartments. The results show that endolymph is extremely inhomogenous with respect to calcium potentials. On the basis of these potentials, it appears that calcium is transported into endolymph in the cochlea and out of endolymph in the saccule and utricle. The possibility that endolymphatic hydrops arises from a disturbance in longitudinal flow of calcium, rather than in longitudinal volume flow, is considered.

Animals↗

Turnover of sulphated macromolecules in the murine endolymphatic sac after long-term kanamycin treatment.

Radioactively labeled sulphur was injected into 12 mice of the NMRI strain 20 days after pretreatment with kanamycin. The animals were decapitated after intervals ranging from 2 minutes to 24 hours after injection. After a routine autoradiographic procedure, darkly stained silver grains were detected in the endolymphatic sac (ES) and its surroundings. One hour after injection, the grains were found in the surrounding blood vessels. Eleven hours later, maximal uptake was seen in the epithelial cells of the ES in the kanamycin-treated animals. Twenty-four hours after injection, a faint S35 uptake in the ES could still be detected. An increase in the ES activity, indicated by an increased number of free-floating cells and the secretion of a sulphur-containing intraluminal substance, did not occur. The spreading pattern of sulphur, as shown in this investigation, does not support the theory that waste products from the inner ear, transported to the ES by the longitudinal flow, produces an increased activity in the sac after long pretreatment with kanamycin. In 12 control animals, no difference in the distribution of labeling was observed, but there was an additional uptake in the free intraluminal cells which was not seen in the kanamycin group.

Animals↗

Ultrastructure of the vestibular sensory organs in delayed endolymphatic hydrops.

Vestibular sensory organs were examined ultrastructurally in two cases of delayed endolymphatic hydrops. The patients, two women, 27 and 16 years of age, suffered profound sensory hearing loss in childhood and experienced severe, recurrent vertigo. Specimens were obtained by a translabyrinthial vestibular nerve transection. We studied the utricular macula and the lateral and posterior cristae in one case, and the utricular macula, the anterior and posterior cristae, and the vestibular ganglion in the other. The otoconia and the otoconial membrane, the sensory epithelia, and the vestibular ganglion appeared fairly normal. Although the entire vestibular end organs were not studied in these cases, it was surprising that the ultrastructural findings did not conclusively identify vestibular end organ pathology as the cause of the vertigo attacks.

Adolescent↗