Acta Oto-Laryngologica

ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20

Pathophysiology of Inner Ear Fluid Imbalance S. K. Juhn, K. Ikeda, T. Morizono & M. Murphy To cite this article: S. K. Juhn, K. Ikeda, T. Morizono & M. Murphy (1991) Pathophysiology of Inner Ear Fluid Imbalance, Acta Oto-Laryngologica, 111:sup485, 9-14, DOI: 10.3109/00016489109128038 To link to this article: http://dx.doi.org/10.3109/00016489109128038

Published online: 08 Jul 2009.

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Date: 30 March 2016, At: 21:30

Acta Otolaryngol (Stockh) 1991; Suppl. 485: 9-14

Pathophysiology of Inner Ear Fluid Imbalance S. K. JUHN, K. IKEDA, T. MORIZONO and M. MURPHY From the Department oJ’Oloiaryngology, Clniiiersity of Minneso !a Medical School, Minneapolis, M N 55455, LISA

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Juhn SK, lkeda K, Morizono T, Murphy M. Pathophysiology of inner ear fluid imbalance. Acta Otolaryngol (Stockh) 1991: Suppl. 485: 9-14. Maintenance of homeostasis of inner ear fluids and biochemical integrity of inner ear tissue are essential for proper functioning of the auditory and vestibular end organs. Although various regulatory mechanisms exist in a different portion of the labyrinth, the inner ear is known to respond to systemic challenges. The association of Meniere’s syndrome with an imbalance of inner ear fluid homeostasis has been hypothesized for the past century. Among many factors, the effects of hormonal imbalance on inner ear fluid composition and inner ear function have however scarcely been studied. The purpose of this study was to explore the relationship between the autonomic nervous system and inner ear function and possible mechanisms of functional disturbances in an experimental condition. An infusion of supraphysiologic amounts of epinephrine, a stress related hormone, resulted in an elevation of osmolality in serum and perilymph. Furthermore, the infusion of epinephrine resulted in elevation of threshold, prolongation of latency, and depression of amplitude in the compound action potential of the auditory nerve. These findings were most marked at high frequencies. We hypothesized that the epinephrine-induced hearing loss was brought about by an increase in perilymphatic osmolality, as well as by the ionic imbalance caused by the osmotic gradient. Since emotional stress has been implicated as a mechanism of inducing a Meniere’s attack, evaluation of the relationship between the autonomic system and cochlear function may contribute to the understanding of possible mechanisms of inner ear dysfunction caused by hormonal imbalances. Key ulords: inner ear ,fluids, osnzolality3epinephrine. hfcniere’s disease.

INTRODUCTION The inner ear fluids have important roles in maintaining auditory and vestibular functions. Their unique biochemical compositions generate appropriate electrical potentials in the auditory and vestibular systems. The inner ear fluids maintain their unique composition by several mechanisms, namely ionic pumps. constant blood supply and blood-labyrinth barriers (I). By exploring the factors that can change the composition of the inner ear fluids and that bring about functional anomalies, it is possible to better understand the mechanisms that maintain the homeostasis of inner ear fluids under physiological conditions. Attempts have been made to measure the mode of reaction of the inner ear in response to systemic challenges (2). I t was found, in general, that the inner ear responds to systemic as well as to non-invasive local challenges through the round window membrane (3). However, it is not well established how biochemical changes of the inner ear fluids are reflected in the functional changes of the inner ear. Endolymphatic hydrops has been advocated as a pathological correlate of Meniere’s disease. However, it has been reported that some patients with idiopathic endolymphatic hydrops did not exhibit clinical Meniere’s syndrome (4). Several factors can be considered to cause membrane displacement in the inner ear. Experimental obliteration of endotymphatic ducts has been reported to produce endolymphatic hydrops ( 5 ) . Hypersecretion or malabsorption of the endolymph can cause imbalance of the ionic composition as well as changes of the osmotic pressure in the inner ear fluids. Alteration of the permeability of blood vessels and cellular membranes in endolymphatic or perilymphatic tissues may be another factor to cause membrane displacement in the inner ear. Jahnke (6) suggested the possibility of membrane

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displacement by the change of permeability of the barriers in the inner ear. However, no specific causative agents have been mentioned. Adrenergic innervation of the cochlear vessels has been demonstrated (7) as well as catecholaminergic effects on cochlear action potentials (8), supporting the notion that catecholamines play an important role in cochlear physiology. The effects of systemically administered catecholamines on the cochlea fluid composition, on the other hands, have scarcely been studied. Juhn et al. (9) reported an increased level of prostaglandin E, (PGE,) as well as an increase in osmolality in perilymph following systemic administration of epinephrine in animals. The present study was undertaken to further elucidate the functional and biochemical effects of epinephrine on the inner ear and to shed some light on how stress potentially affects patients with Meniere’s disease. MATERIAL AND METHODS Healthy chinchillas weighing 450-600 g were used in the present experiments. Each animal was anesthetized with an intramuscular injection of ketamine chloride (40 mg/kg) and supplementary dosages of 20 mg/kg were given hourly. Epinephrine was dissolved in physiological saline (0.535 mg/ml) with a few drops of HCI. The left femoral vein was then surgically exposed and cannulated with polyethylene tubing. The syringe was attached to the infusion pump and set to a flow rate of 0.70 ml/h. Epinephrine was infused at 6.3 pg/min. Control animals were treated with 0.9% physiological saline. Samples of blood and perilymph were collected in three groups of animals at 30, 60 and 180 min after infusion. Osmolality was measured using a Wescor 5500 Vapor Pressure Osmameter. The compound action potential (CAP) of the auditory nerve was measured before and 3 h after the infusion of epinephrine. A closed acoustic system with probe microphone was used to deliver and monitor an asynchronous tone burst (1-ms riselfall, 10-ms plateau) at 2, 3 , 4 , 6, 8, 12. 16 kHz with a maximum sound level of 70 dB SPL. A fenestra was made in the bulla and a silver wire was placed on the round window membrane. The CAP amplitude was measured from the first negative peak to the subsequent positive peak of the waveform. The CAP threshold was defined as 10 pV amplitude. The CAP latency was the time between the onset of the sound at the tympanic membrane and the first negative peak. RESULTS The osmolality of serum and perilymph after epinephrine infusion is shown in Figs. 1 and 2. The osmolality increased significantly both in serum and perilymph at each time after epinephrine infusion. The increase of perilymph osmolality appeared to parallel the increase in serum osmolality. The effects of epinephrine o n the CAP threshold are shown in Fig. 3. The CAP threshold was significantly elevated at all frequencies. The shift of the CAP threshold due to epinephrine had a tendency t o increase at higher freuqencies. The input-output curves at 3, 6 and 12 kHz before and after the infusion of epinephrine are shown in Fig. 4. The depression of the CAP amplitude with the lowering of the intensity was marked, especially at 12 kHz. The CAP latency characteristics before and after epinephrine infusion are shown in Fig. 5. As the intensity of the tone stimuli was decreased, the CAP latency was prolonged. DISCUSSION The mode of response of the inner ear t o systemic administration of biological materials provides important information concerning the mechanisms of maintaining homeostasis and

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how this balance can be disturbed, and what kind of functional changes take place after this homeostasis is disturbed. The results of the present study clearly demonstrated that systemic infusions of epinephrine increased perilymph osmolality and altered cochlear electrophysiology. The changes in electrophysiology observed are consistent with the observation reported by Muchnik et al. (8),in which intraarterial injection of epinephrine and norepinephrine significantly elevated CAP threshold and prolonged CAP latency. The present study is in agreement with their study and we were able to describe more detailed changes in the CAP response. Concerning the mechanisms of changes of cochlear electrophysiology, several factors can be speculated on. The observed elevation of perilymph osmolality may have altered the mechanical or electrical properties of the hair cells resulting in electrophysiological changes. Dulon found that isolated hair cells in vitro consistently and predictably shortened or lengthened in response to the toxicity of the surrounding fluid (10). These changes were rapid and reversible. He further postulated that small, fluctuant changes in cochlear fluid osmolality might lead to microchemical changes in the hair cells which could manifest as audiologic dysfunction. The elevated CAP threshold was more pronounced at higher frequencies. The depression of amplitude and the prolongation of latency were also pronounced at higher frequencies. These findings imply that outer hair cells might be responsible for these changes. A similar pattern was observed under ototoxic exposure to kanamycin ( I I ) , nitrogen mustard-N-oxide (12) and acoustic overstimulation. Furthermore, the distinct changes in CAP response at low intensity might be explained by the effects outer hair cells have on inner hair cells (13).

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It is clear that epinephrine elevates serum osmolality. Juhn (14) showed that increased serum osmolality, produced by systemic injection of glycerol, led to elevated perilymph osmolality. Since epinephrine can raise serum osmolality, perilymph osmolality elevation may be partially due to serum osmolality changes. The perilymph osmolality would most likely be increased by free water movement into the surrounding tissues, but also possibly by the transport of osmotically active substances into the perilymph. Epinephrine also elevates systemic blood pressure which may produce a secondary effect on cochlear fluidlion homeostasis. Epinephrine elevates blood pressure by increasing cardiac output (increasing rate and contractility) and increasing peripheral resistance (by arteriolar vasoconstriction). Increased blood pressure has been shown to disrupt endothelial tight junctions in the brain leading to a breakdown of the blood-brain barrier and increased penetrance of substances into the CSF ( 1 5 , 16). A similar mechanism may be at work in the cochlea. Disruption of the blood-labyrinth barrier may lead to increased passage of biochemical substances into perilymph. High systemic blood pressure may also increase hydrostatic pressure in the cochlea resulting in increased fluid flow into perilymph or endolymph, possibly contributing to endolymphatic pressure change. One of the most characteristic actions of epinephrine is vasoconstriction of peripheral vessels. Adrenergic innervation of cochlear vessels has been demonstrated (7) and u-adrenergic receptor regulation of cochlear vessels has been described (1 7, 18) indicating that inner ear

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vessels may constrict in response to epinephrine. Some authors have suggested that epinephrine leads to decreased perfusion in cochlear vessels (19) while others have argued that epinephrine leads to increased cochlear blood flow (9, 20). This apparent dichotomy may be explained by looking at the systemic and local effects of epinephrine. Local epinephrine may cause vasoconstriction in cochlear vessels leading to decreased blood flow, but epinephrine systemically elevates blood pressure and heart rate, which overcomes the cochlear vasoconstriction to increase cochlear blood flow (21). It is possible that a decreased blood supply to the organ of Corti via a-adrenergic vasoconstriction may lead to dysfunction of the organ of Corti and that this in turn leads to the electrophysiologic results observed in our experiments. The increased distribution of regional blood flow from the apex to the base of the basilar membrane (22, 23) may provide a reasonable interpretation of the damage noted in the higher frequencies. It is quite conceivable that epinephrine may alter the inner ear fluid homeostasis by stimulating production of prostaglandins which in turn may stimulate or inhibit cAMP production. An elevation of increased PGEz levels in perilymph after epinephrine infusion has been reported (9). Effects of catecholamine on the synthesis of prostaglandins have been reported in the kidney (24), in the brain (25) and in the iris (26). PGEz has been shown to increase cAMP in various tissues (27, 28), which may lead to altered ion permeabilities and fluid secretion. One could speculate that an elevation of PGE2, induced by epinephrine, alters permeability of the cochlear membranes to ions, and this may be another mechanism of the perilymph osmolality changes observed in this study. In summary, systemic infusion of epinephrine in the chinchilla produced significant increases in perilymph osmolality and changes in cochlear electrophysiology (elevated CAP threshold, prolonged latency and decreased amplitude). These changes may have been produced by the effect of epinephrine on the cochlear microcirculation or changes in perilymph/endolymph ion concentrations or osmolality. Because epinephrine is a major component of anxiety and the stress response which may be associated with Meniere's syndrome or attack, it is important to further investigate its effects on the inner ear. Epinephrine also provides a valuable tool with which to study the intricate interactions and homeostatic mechanisms of the inner ear. ACKNOWLEDGEMENTS The authors are grateful for the excellent technical assistance of Christopher Lees. This work was supported in part by an R & D fund from Pharmacia AB, Uppsala, Sweden.

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Pathophysiology of inner ear fluid imbalance.

Maintenance of homeostasis of inner ear fluids and biochemical integrity of inner ear tissue are essential for proper functioning of the auditory and ...
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