Wagner Niels, Cayé-Thomasen Per, Laurell Göran, Bagger-Sjöbäck Dan, Thomsen Jens
Department of Otorhinolaryngology, Gentofte University Hospital of Copenhagen, Hellerup, Denmark.
Acta Otolaryngol. 2005 Apr;125(4):340-5. doi: 10.1080/00016480510026881.
Gentamicin-induced cochlear hair cell loss depends on local middle ear administration kinetics and the total drug dose. Single-dose gentamicin instillation in the middle ear is associated with a high variation in hair cell loss.
To compare the effects of single-dose and continuous round window administration of gentamicin on cochlear hair cell loss in a guinea pig model.
Two methods for drug administration to the inner ear were used. In groups of five animals, a total dose of 0.8 or 3.2 mg of gentamicin was either instilled as a single dose directly into the round window niche or administered continuously over a 1-week period using a pump-catheter system. Continuous administration was achieved by means of a posterior tympanotomy and subcutaneous placement of an osmotic pump fitted with a catheter. The tip of the catheter was fixed in the round window niche. One group of five animals served as controls and received a saline infusion. The animals were sacrificed after 1 week and hair cell loss was determined microscopically after dissection and phalloidin labelling of the basilar membrane and organ of Corti.
Quantitation of cochlear hair cell loss revealed a dose-dependent effect of gentamicin. With both treatment modalities the higher dose induced a higher percentage of hair cell loss. There was inner and outer hair cell loss in all four groups that received gentamicin. With the single-dose instillation, hair cell loss was distributed irregularly from the round window membrane towards the cochlear apex, whereas continuous administration induced hair cell loss close to the round window membrane. Single-dose instillation induced greater hair cell loss than continuous administration at the same dose. The inter-individual variation in hair cell loss was highest following single-dose instillation.
庆大霉素诱导的耳蜗毛细胞损失取决于中耳局部给药动力学和药物总剂量。中耳单剂量滴注庆大霉素与毛细胞损失的高度变异性相关。
在豚鼠模型中比较庆大霉素单剂量和连续经圆窗给药对耳蜗毛细胞损失的影响。
采用两种内耳给药方法。将每组五只动物，分别将0.8或3.2mg庆大霉素作为单剂量直接滴入圆窗龛，或使用泵导管系统在1周内连续给药。通过后鼓室切开术和皮下放置装有导管的渗透泵实现连续给药。导管尖端固定在圆窗龛内。一组五只动物作为对照，接受生理盐水输注。1周后处死动物，在解剖并对基底膜和柯蒂氏器进行鬼笔环肽标记后，显微镜下确定毛细胞损失情况。
耳蜗毛细胞损失的定量分析显示庆大霉素有剂量依赖性效应。两种治疗方式中，较高剂量均导致更高百分比的毛细胞损失。接受庆大霉素的所有四组均有内毛细胞和外毛细胞损失。单剂量滴注时，毛细胞损失从圆窗膜向耳蜗顶端呈不规则分布，而连续给药导致靠近圆窗膜处的毛细胞损失。在相同剂量下，单剂量滴注比连续给药诱导的毛细胞损失更大。单剂量滴注后，毛细胞损失的个体间差异最大。
