Extracellular adenosine 5′-triphosphate (ATP) in the endolymphatic compartment influences cochlear function

There is strong evidence for the presence of P₂ purinoceptors on cochlear tissues, but the role of extracellular ATP in cochlear function is still unclear. Our previous have determined the presence of ATP in the cochlear fluids and indicated that the purinoceptors are substantially localized to the tissues lining the endolymphatic compartment. This implies that extracellular ATP may have an humoral role confined to the endolymphatic space. In order to study the influence of extracellular ATP in the endolymphatic space, a series of studies were undertaken in which ATP (10 μM to 10 mM) in artificial endolymph (EL) (test solution: 2–12.5 nl) was injected into the scala media and the effect on the cochlear microphonic (CM) and endocochlear potential (EP) evaluated. A double-barrelled pipette, with one barrel containing the test solution and the other artificial EL (control solution) was inserted into scala media of the third turn of the guinea-pig cochlea. A known volume (2–12.5 nl) of test or control solution was then pressure-injected into the space. ATP had a significant dose-dependent suppressive effect on both EP and CM with a threshold of approximately 2×10⁻¹⁴ mol; the response was readily reversible, also in a dose-dependent fashion. Artificial EL of the same volume had no effect on EP and CM. The ATP effect on EP was blocked by the P₂ purinoceptor antagonists suramin and reactive blue 2 (RB2). Neither adenosine (2×10⁻¹³ to 2×10⁻¹¹ mol) nor suramin or RB2 on their own had any effect on EP and CM. This study provides the first evidence for an effect of extracellular ATP in the endolymphatic compartment on cochlear function which is mediated via P₂ purinoceptors. This provides supporting evidence for an humoral role for extracellular ATP in the modulation of cochlear function.     

局部和全身给药后泼尼松龙在外淋巴液中的浓度分析

目的 :比较局部和全身给药后 2 1 氢化琥珀酸 泼尼松龙在外淋巴液中的药物动力学。方法 :将实验豚鼠分组 ,局部用药 (局部组 ) :将 0 .5 %的 2 1 氢化琥珀酸 泼尼松龙液在直视下置于圆窗龛 ;全身用药 (全身组 ) :按 6 0mg/kg腹腔内注药 ;两组均以生理盐水作为对照。分别于给药后不同时间段采集外淋巴液标本 ,采用高压液相色谱法 (HPLC)测定药物浓度。结果 :局部组药物最高浓度出现在给药后 180min ,为 (95 2 .3± 382 .7)mg/L ,并在 96 0min后维持在 (18.72± 16 .97)mg/L。全身组药物最高峰时间在给药后 15 0min ,为 (14 .71± 7.0 5 )mg/L。结论 :局部给予 2 1 氢化琥珀酸 泼尼松龙 ,可以获得长时间、高浓度的药物水平。     

海藻酸钠地塞米松凝胶圆窗给药后外淋巴液中地塞米松浓度的变化

目的 分析海藻酸钠地塞米松凝胶(Alg-Dex凝胶)经圆窗给药后地塞米松在外淋巴液中的浓度变化.方法 健康豚鼠30只随机分成5组,每组6只,于每只豚鼠单侧(右耳)经圆窗给海藻酸钠地塞米松凝胶(45 mg/ml)20 μl后的1、2、3、4、5天分别用高压液相色谱仪分析外淋巴液中的地塞米松浓度.结果 在Alg-Dex凝胶给药后1、2、3、4、5天在外淋巴液中均能检测到地塞米松,浓度分别为0.49±0.06、1.32±0.28、0.65±0.08、0.66±0.05、0.53±0.17 mg/L,其中第2天浓度最高(1.32±0.28 mg/L),第3～5天药物浓度较稳定,平均浓度为0.61±0.07 mg/L.结论 海藻酸钠能作为地塞米松良好的缓释载体,使其缓慢、持续地经圆窗膜渗透到外淋巴液中.     

Increased noise trauma in guinea pigs through magnesium deficiency

Summary Mg-deficient guinea pigs developed significantly increased hearing loss during 4 weeks of noise exposure [95 dB(A)] as compared to animals fed a Mg-rich diet. The hearing loss was negatively correlated to the Mg content of the perilymph (r=–0.86). Besides this auditory effect, there was a decrease of intracellular Mg and an increase of collagen in the myocardium, both of which were correlated to the hearing loss and caused by Mg deficiency and noise stress.     

硒拮抗顺铂耳毒的实验研究

用无焰原子吸收分光光度法测定了豚鼠内耳外淋巴的电解质成份．：Ｎａ、Ｋ、Ｚｎ、Ｍｇ，旨在从外淋巴这些离子变化中观察顺铂对内耳的毒性作用及硒人毒性的拮抗作用，由实验测得正常豚鼠鼓阶中各离子平均浓度（ｍｇ／Ｌ）分别为２９４５．８，３４５．９，１２６．６，８５．１，前庭 分别为１３７９．１，１７４５．２，１２５．４。８８．６。鼓阶中Ｎａ浓度高于前庭阶（Ｐ〈０．０１）；鼓阶中Ｋ浓度低于前庭（Ｐ〈０．０１），     

The ultrastructure of the supporting system in the guinea pig semicircular canal

Summary The ultrastructure of the perilymphatic space of the guinea pig semicircular canal was examined, using thin sectioning, scanning electron microscopy and freeze-fracture methods. The perilymphatic space was divided into two parts: an area of fibrous matrix and an area of fibroblasts with bundles of fine filaments. In the area of fibroblasts, cell processes and filament bundles formed a meshed pattern. The cell processes were interconnected with each other by both intermediary and gap junctions. The inner surface of the osseous semicircular canal was covered with multilayers of cell processes of both fibroblasts and mesothelial cells. The fact that tight and gap junctions were observed between the cell processes suggests a functional significance in these structures.     

豚鼠硫辛酸鼓室与静脉给药的内耳药代动力学比较

目的 比较静脉与鼓室给药,应用高效液相色谱技术(high-performance liquid chromatography,HPLC)研究豚鼠外淋巴中的硫辛酸(lipoic acid,LA)药代动力学特征,为临床选择给药方式和药物剂量提供参考.方法 54只豚鼠随机分为2组,每组27只,分别经鼓室和静脉给予LA,给药质量浓度为100 mg/ml.于给药后0.5、1、2、3、4、5、6、8、10 h用HPLC检测豚鼠外淋巴中LA的质量浓度.结果 豚鼠外淋巴中LA质量浓度在0.1～200μg/ml范围内线性关系良好(r~2=0.9996),鼓室给药后外淋巴检测到最大药物质量浓度为171.7 μg/ml,而静脉给药组为33.7 μg/ml;静脉给药组动物的药物平均滞留时间为2.9 h,鼓室给药组为3.7 h;静脉给药组药物的半衰期为2.1 h,鼓室给药组为1.8 h.结论 豚鼠LA静脉与鼓室给药后均能在外淋巴中检测到药物,但鼓室局部给药效果明显优于静脉全身给药.     

Changes in CMDP and DPOAE during acute increased inner ear pressure in the guinea pig

During and after an increase of inner ear pressure, induced by injection of artificial perilymph, the 2f ₁ − f ₂ and f ₂ − f ₁ distortion products (DPs) in cochlear microphonics (CM) and otoacoustic emissions (OAE) were recorded in the guinea pig. An inner pressure increase of ∼600 Pa gave only small changes in CMDP and DPOAE. Along with a decrease in f ₁ amplitude, a small decrease in amplitude of the 2f ₁ − f ₂ and a small increase in the f ₂ − f ₁ were measured in CM. This matches a shift from a symmetrical position of the operating point for hair cell transduction, leading to an increase in even-order distortion and a decrease in odd-order distortion. Similar, a decrease in 2f ₁ − f ₂ DPOAE was expected. This might be the case at the generation sites but this effect was then more than compensated for by a better middle ear transfer, accounting for the increase of 0.4 dB of the 2f ₁ − f ₂ DPOAE amplitude. In conclusion, changes of overall inner ear fluid pressure have minor effects on cochlear function. This is a relevant finding for further understanding of diseases with changed inner ear fluid volumes, as Ménière’s.     

High potassium-induced glutamate release in the cochlea: in vivo microdialysis study combined with on-line enzyme fluorometric detection of glutamate

The time course of changes in perilymphatic glutamate release and their Ca²⁺-dependency were studied in the guinea pig cochlea during high K⁺-evoked depolarization. The glutamate concentration was analyzed continuously by an enzyme-linked fluorometric assay combined with microdialysis. Two peaks of glutamate increase were found in response to perfusion for 10 min. In the absence of Ca²⁺, the first peak was diminished, whereas the inhibition of the second peak was minimal.     

Critical Evaluation of Round Window Membrane Sealing in the Treatment of Idiopathic Sudden Unilateral Hearing Loss

ObjectivesRupture of the round window membrane with consecutive development of a perilymphatic fistula (PLF) is still a matter of controversial debate in the pathogenesis of idiopathic sudden sensorineural hearing loss (SSHL). Until now no consensus exists about whether these patients benefit from performing an exploratory tympanotomy with sealing of the round window. The aim of the present study was to analyze critically the effectiveness of sealing the round window membrane in patients with SSHL.MethodsThe clinical data of 51 patients with SSHL and a mean hearing decline of at least 60 dB over 5 frequencies who were treated with tympanotomy and sealing of the round window membrane were retrospectively analyzed. The results have been compared to the current state of the literature.ResultsIntraoperatively a round window membrane rupture or fluid leak was observed in none of the patients. After performing tympanotomy the mean improvement of hearing level was 32.7 dB. Twenty of 51 examined patients (39.2%) showed a mean improvement of the hearing level of more than 30 dB and a complete remission could be detected in 12 patients (23.5%). Reviewing the literature revealed no standard guidelines for definition or treatment of SSHL as well as for evaluation of hearing loss and its recovery.ConclusionThe results of the present study and the literature should be discussed critically. It is unclear whether tympanotomy and sealing of the round window membrane may be a meaningful treatment for SSHL. Therefore this procedure should be discussed as a therapeutic option only in selected patients with sudden deafness or profound hearing loss in which PLF is strongly suspicious or conservative treatment failed.