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Organic acid transport into the cochlear perilymph.

The passage of exogenous organic and inorganic substances from blood into perilymph is likely to be controlled by the blood-perilymph barrier. This report reviews published data on the transfer of ten exogenous organic acids from the blood into the perilymph of experimental animal models. Although the range of the molecular weights of these acids is within half an order of magnitude, major differences exist in the perilymph concentration as a percentage of simultaneous serum concentration. Furthermore, these studies show that, contrary to previous suggestions, non-ototoxic compounds can achieve marked concentration gradients within the perilymph.

Acids↗

Distribution of marked perilymph to the subarachnoidal space.

In guinea pigs the tympanic perilymph of the basal turn was marked with fluorescing rhodamine. In the first series one drop of a 2% solution of the dye was applied onto the round window membrane. Since the perilymphatic space was not opened, the physiologic state of the communicating fluids perilymph and CSF was maintained. The dye appeared within 3-5 min via cochlear aqueduct in the subarachnoidal space. In the dead animal the speed of distribution was significantly less. This most probably indicates a weak physiologic flow of the perilymph through the aqueduct to the subarachnoidal space in living animals. In the second series, 2 ng of lyophilized rhodamine was instilled directly into the tympanic perilymph near the round window. Though hardly any additional volume was brought into the perilymph, the distribution of the dye was distinctly greater as a sign of the considerable sensitivity of the fluid system, even by the slightest manipulation.

Animals↗

Taurine entry into perilymph of the guinea pig.

Taurine is a beta-aminosulfonic acid and is a ubiquitous amino acid whose role in the cochlea is not well established. In this study, its entry from blood into perilymph was investigated in the guinea pig as animal model. The penetration rate of [3H]taurine (molecular weight 125) into the perilymph of the scala vestibuli was measured 1 and 2 h after the intravenous infusion of [3H]taurine in nephrectomized animals. Results showed a rate of penetration in perilymph related to plasma at 36 +/- 4.7% (n = 5) after 1 h and 43 +/- 5.6% (n = 5) after 2 h. Compared to the penetration rate of urea (molecular weight 60) and mannitol (molecular weight 186) reported previously in rats, a passive entry of taurine into perilymph through the blood-perilymph barrier is suggested.

Animals↗

Apical cochlear nerve exposed to perilymph in the gerbil and rat.

There is considerable controversy regarding the origin and composition of perilymph in the scala vestibuli and scala tympani and the barriers and transport mechanisms between them. To elucidate the anatomical separation between perilymph and the extracellular fluid which surrounds the cochlear nerve in Mongolian gerbils (Meriones unguiculatus) and Sprague Dawley rats (Rattus rattus) we examined the modiolus, osseous spiral lamina and the bone of the perilymphatic scalae using light and electron microscopy. Although the cochlear nerve, spiral ganglion and their extracellular fluid are separated from perilymph by the bone of the modiolus in the middle and basal turns, no bone separates these neural structures from perilymph in the apical turn in the two species examined. Instead, the spiral ganglion and axonal elements of the apical turn were covered by a continuation of the bone lining cell layer of the scala tympani. Gaps between lining cells appeared to provide direct communication between the perilymphatic fluid and the extracellular fluid investing the cochlear nerve. Various authors have described openings in modiolar bone in both the scala vestibuli and the scala tympani. While the bone and cellular covering of the modiolus in the basal middle turns of the cochlea is not presumed to be a complete barrier to fluid exchange between the two scalae and the modiolar canal it can be expected to impose some limitation on the rate of passive diffusion. Therefore our data indicates that in the apical turn of the Mongolian gerbil and Sprague-Dawley rat there may be a more significant communication between perilymph and the extracellular fluid and neural elements of the apical modiolar canal than previously reported.

Animals↗

Asphyxia and depolarization increase adenosine levels in perilymph.

Extracellular adenosine has been suggested as a modulator of cochlear function. To date the release of adenosine into the extracellular spaces of the cochlea has not been demonstrated. Therefore, experiments were designed to examine whether adenosine release into perilymph could be detected in response to depolarization by high potassium concentrations or in response to asphyxia. For this purpose, the perilymph compartment of guinea pigs was perfused with an artificial perilymph and the effluent assayed for ATP, ADP, AMP and adenosine. Results indicate that potassium induced a slight, significant increase and asphyxia induced a very large, significant increase in adenosine levels in perilymph effluent. No changes in the levels of the other compounds were measured. It is concluded that depolarization and asphyxia can induce the release of adenosine into perilymph.

Adenosine↗

Transport characteristics of the blood--perilymph barrier.

The inner ear must maintain a delicate homeostasis to preserve high sensitivity to acoustic and vestibular inputs. Various experimental conditions were imposed upon chinchillas to help identify these homeostatic mechanisms for the inner ear fluids. Radioactive ions (sodium, chloride, and calcium) pass into perilymph more slowly than they pass into cerebrospinal fluid or aqueous humor. The concentration of glucose in perilymph relative to that in serum was found to be quite constant (about 45 per cent) over a wide range of serum values (130-943 mg/dl) generated by continuous intravenous infusion. The transport of albumin into perilymph was very slight after injection of the radioactive protein intravenously. Osmotic agents cause an efflux of water from perilymph into a relatively hypertonic circulating blood, resulting in a secondary elevation of perilymph osmolarity. Recent findings relating to cyclic AMP metabolism and the possible role of this second messenger in the regulation of inner ear fluid metabolism are discussed. A new hypothesis that excess cyclic AMP in the inner ear may be related to endolymphatic hydrops is presented.

Animals↗

Sodium, potassium, chloride and calcium concentrations measured in pigeon perilymph and endolymph.

According to Davis' (1965) model of the inner ear, a potential difference between the endocochlear potential and the hair cell resting potential drives the transduction current across the apical hair cell membrane. It is assumed that the endocochlear potential (EP) consists of two components. The first is a diffusion potential, which depends on the ionic composition of endolymph and perilymph and on the permeability of the perilymph-endolymph barrier. The second is an electrogenic component which is determined by active ion transport across the perilymph-endolymph barrier. In birds, the EP is between +8 and +20 mV. Little is known about the underlying mechanisms responsible for the measured EP in birds. The present paper studies whether ionic compositions of endo- and perilymph might explain the EP in birds. Concentrations of Na+, K+, Ca2+ and Cl- in pigeon scala vestibuli, scala tympani and scala media were determined with ion-selective microelectrodes. Na+, K+, Ca2+ and Cl- were 150.0, 4.2, 1.4 and 117.0 mM in perilymph (scala tympani and scala vestibuli). In scala media, the concentrations of K+, Ca2+ and Cl- were 140.6, 0.23 and 142.1 mM.

Animals↗

"Floating" labyrinth. Pathophysiology and treatment of perilymph fistula.

Collapse of the membranous labyrinth of the pars superior is a morphological change observed in 50% of animals with experimentally produced perilymph fistula, although the extent and degree of the collapse may vary greatly. The moderately collapsed membranous labyrinth may drift with CSF and/or perilymph pressure changes and this may stimulate sensory cells of the utricle and/or semicircular canals if the sensory cells are intact and the collapsed wall is in contact with the otolithic membrane and/or cupula. This condition is termed "floating" labyrinth. Caloric irregularity is often observed in electronystagmograms recorded from animals with experimental perilymph fistula. This is also observed in patients with perilymph fistula. Partial destruction of the vestibular organs using argon laser was performed in a patient with perilymph fistula who was incapacitated because of persistent positional vertigo after closure of the oval window fistula. Irradiation of the argon laser beam was directed to the macula utriculi, utriculoampullary nerve and singular nerve. The hearing of the patient was maintained, and vertigo disappeared after laser labyrinthectomy.

Audiometry, Pure-Tone↗

Beta-2 transferrin: limitations of use as a clinical marker for perilymph.

Beta-2 transferrin is a protein marker that can be used in the clinical setting to reliably identify the presence of cerebrospinal fluid (CSF). Recent literature has suggested that beta-2 transferrin can also be used as a clinical marker for perilymph. This study investigates the use of a beta-2 transferrin assay as a method to identify the presence of perilymph. Twenty-two patients were enrolled in the study. Fluid samples were obtained intraoperatively and tested for the presence of beta-2 transferrin. As expected, four CSF samples collected were positive for beta-2 transferrin; however, four known perilymph samples collected from patients undergoing cochlear implantation were negative for beta-2 transferrin, seven of nine known perilymph samples obtained during stapedectomies were negative for beta-2 transferrin, and four of five samples collected during middle ear explorations for fistula were negative for beta-2 transferrin. With current methodology beta-2 transferrin does not appear to be a reliable clinical marker for perilymph in the operative setting.

Biomarkers↗

Hearing loss and trace elements Fe2+ and Zn2+ in the perilymph.

Fe2+ and Zn2+ levels in perilymph of guinea pigs injected with gentamicin (GM) were examined and compared with the corresponding concentrations in CSF, serum and hairs. We observed a preventive and therapeutic action of sea buckthorn oil and injectio gastrodini to hearing loss. The results showed that: (1) the Fe2+ content in GM-injected guinea pigs was increased in perilymph and hairs; it was decreased after prevention and treatment, but there was no obvious change in CSF and serum; (2) the Zn2+ content in perilymph and CSF was increased in GM-injected guinea pigs. It rose further after prevention, but in serum and hairs it decreased. The results indicate that the ototoxic reaction to GM is related to the rise of the Fe2+ content in perilymph. The elevation of Zn2+ is a compensatory reaction. The changes in the chemical composition of perilymph are more important than those in CSF, serum and hairs for pathological changes of the cochlea. Sea buckthorn oil can prevent GM ototoxicity.

Animals↗

Pharmacokinetic profiles of ceftazidime in cochlear perilymph, cerebrospinal fluid and plasma: a high-performance liquid chromatographic study.

A pharmacokinetic profile of the antibiotic ceftazidime was established for perilymph, cerbrospinal fluid (CSF) and plasma in 12 guinea pigs using the technique of high-performance liquid chromatography. The mean peak levels of 13.35 mg/l in perilymph and 140.54 mg/l in plasma were reached within the first hour after a single intravenous dose of 100 mg/kg. The CSF mean peak level of 5.36 mg/l, however, was not attained until 3 h after injection. The half-life was about 4 h in perilymph, more than 6 h in CSF and less than 2 h in plasma. Six hours following administration, the perilymph drug concentration remained higher than the plasma level. The study indicates that ceftazidime has excellent penetration into perilymph. It is concluded that ceftazidime should be a very useful agent in the treatment of bacterial labyrinthitis caused by susceptible organisms.

Animals↗

Sudden or fluctuating hearing loss and vertigo in children due to perilymph fistula.

Five cases are presented of children with rapid onset of sensorineural hearing loss, disequilibrium, or both, who were found at exploratory tympanotomy to have a perilymph fistula. Four of the children had histories suggesting that antecedent barotrauma or physical exertion contributed to the development of the fistula. One child with congenital unilateral craniosynostosis had a residual temporal bone abnormality on the same side as the perilymph fistula. Two children had identifiable anatomic abnormalities in the middle ear. A classification of perilymph fistula is proposed that describes a congenital, an acquired, and a combined type of fistula. Inner ear fluid dynamics and patency of the cochlear aqueduct appear to be important factors in pathogenesis. Children with unexplained fluctuating or sudden onset of sensorineural hearing loss, and children with unexplained disequilibrium or vertigo should be suspected of having a perilymph fistula. The history can be singularly important in raising the suspicion that a perilymph fistula may be present. Although audiometric, vestibular, and radiographic studies can be helpful, there is no way to prove the presence or absence of a fistula without directly viewing the middle ear. Tympanotomy with repair of the fistula does not assure improvement in hearing.

Adolescent↗

Summating potential/action potential ratio in perilymph fistula.

A prospective study of electrocochleography in patients with clinically suspected perilymph fistula was undertaken to determine its predictive value in that disorder. One hundred forty-four patients suspected of having perilymph fistula had electrocochleography performed--34 of these (39 ears) had exploratory tympanotomy. Of the 19 ears with normal preoperative summating potential/action potential (SP/AP) ratio, ten had perilymph fistula identified at the time of surgery. Of the 20 ears with abnormal SP/AP ratio, 16 had perilymph fistula confirmed at exploration, 18 had resolution of symptoms after oval window and round membrane grafting, and only one ear had postoperative persistence of the abnormal SP/AP ratio. This study suggests that an abnormal SP/AP ratio is not only predictive of endolymphatic hydrops, but also of perilymph fistula (both problems of inner ear fluid imbalance). This study also suggests that, while abnormal SP/AP ratio is fairly specific for inner ear fluid imbalance, it is not sensitive.

Adolescent↗

Free amino acid analysis of guinea pig perilymph: a possible clinical assay for the PLF enigma?

Controversy prevails regarding the accuracy of the clinical diagnosis of perilymphatic fistula (PLF). The diagnosis of PLF has been based on the subjective evaluation of vestibular function tests and the intraoperative macroscopic visualization of "clear fluid" from the oval/round windows at the time of exploratory tympanotomy. However, the subjective visual characterization of PLF varies among observing surgeons. Furthermore, perilymph can be "contaminated" with serum, blood, cerebrospinal fluid (CSF), and local anesthesia. This article presents a scientific biochemical microassay for the free amino acid profile of perilymph. Microaliquots of uncontaminated perilymph were sampled from the bilateral round windows (scala tympani) of 20 guinea pigs and analyzed for 19 free amino acid concentrations (FAAC) by high-performance liquid chromatography (HPLC). These samples were compared with the FAAC of guinea pig serum samples. Perfect predictor value ranges were nonoverlapping for 12 of 19 free amino acids in perilymph vs. plasma. Amino acid microassay of middle ear fluid for verification of "true" perilymph vs. nonperilymph fluids by the identification of nonoverlapping FAA markers may allow scientific verification of the existence of PLF in "suspected" patients.

Amino Acids↗

The effect on perilymph of the alteration of serum glucose or calcium concentration.

In the experimentally-induced hyper- or hypoglycemic state, perilymph glucose concentration paralleled the blood concentration, although a delay of about one hour was observed between the time of maximum concentration of glucose in perilymph and its concentration in blood. In hypercalcemia, perilymph calcium concentration steadily increased over a three-hour period, although blood calcium concentration fluctuated during this time. After an initial increase in the CSF calcium concentration, there were insignificant changes during the second and third hours. In animals with thyrocalcitonin-induced hypocalcemia, although blood calcium concentration steadily decreased, its concentration in perilymph and CSF remained practically constant. The present findings suggest that the chemical composition of perilymph can be altered by changing the blood concentration of glucose or calcium. The marked difference of behavior noted between glucose and calcium in these experiments would indicate the existence of different mechanisms for maintaining the homeostatic state for these two substances.

Animals↗

Spontaneous and traumatic perilymph fistulas.

Clinicians have been aware of the problem of post-stapedectomy perilymph fistulas for some time. The existence of non-surgical oval and round window fistulas has been known and was first described in detail by Fee in 1968. This paper concerns a small series of patients with spontaneous and traumatic perilymph fistulas. Five oval window fistulas and one round window fistula are reported. Clinical features, audiometric, radiographic and vestibular findings are discussed. The etiology of traumatic and spontaneous fistulas is not well understood, but seems to bear a relationship to sudden increased in intracranial pressure transmitted to the inner ear through the cochlear aqueduct. Middle ear pressure changes, as seen in acoustic or barotrauma, may also cause these leaks. Indications for surgery and techniques of perilymph fistula identification and repair are discussed in the paper. Surgical correction led to relief of vertigo in 80 percent of patients in this series, and significant hearing improvements were seen in 50 percent of the patients. In evaluating patients with sudden sensori-neural hearing loss, or persistent vestibular symptoms following head or ear trauma, the otologist should keep in mind the possibility of a perilymph fistula and actively investigate these patients. Evidence presented in this paper and in the literature suggest that identification and correction of spontaneous and traumatic perilymph fistulas can lead to resolution of vestibular symptoms and improved hearing in a significant number of patients with these lesions.

Adult↗

Biochemical parameters of guinea pig perilymph sampled according to scala and following sound presentation.

Guinea pigs were exposed to sound varying from 2 to 8 kHz in frequency and 80-100 dB (SPL) in intensity for periods of 1 hr. The biochemical parameters, glucose, sodium, total protein, and the glycolytic enzymes, aldolase, phosphohexose isomerase, and total LDH as well as isozymes of the latter were ascertained for blood serum, perilymph, and, in some instances, cerebrospinal fluid. The three enzymes occurred at lower levels in perilymph as compared to blood serum. Except for a small difference in serum total protein, sound presentation incurred no significant effect on any of the above parameters. Definite differences in several metabolites were discerned for perilymph sampled according to scala and which were independent of the respective acoustical treatments. Thus, as compared to the scale tympani, the scala vestibuli perilymph displayed a higher glucose content and a diminished total LDH level and of the latter isozymes, LDH(1) ranged lower and LDH(2), higher. As further evidence pointing to cerebrospinal fluid as the possible origin of perilymph, similarities in glucose contents and LDH isozyme patterns were noted for both fluids.

Animals↗

[Electrophoretic examination of protein distribution in guinea pig perilymph].

Perilymph and serum of guinea pigs were investigated using immunoelectrophoresis and polyacrylamide gel electrophoresis. The molecular weights of the perilymph proteins were estimated by electrophoresis in a linear polyacrylamide gel gradient (3-20%). The immunoelectropherograms and the polyacrylamide gel electropherograms of equivalent amounts of perilymph protein and serum protein are nearly the same. The immunological detection of the perilymph proteins indicates that they are serum proteins. The clear identification of the individual proteins fails because of missing monospecific antisera against the individual proteins of guinea pig. High-molecular proteins (range of the molecular weight estimation 67 000-290 000) are also detectable in the perilymph according to the molecular weight estimation.

Animals↗