Miettinen S, Laurell G, Andersson A, Johansson R, Laurikainen E
Department of Otolaryngology, Turku University Hospital, Finland.
Acta Otolaryngol. 1997 Jan;117(1):55-60. doi: 10.3109/00016489709117992.
Considerable interindividual variability in the ototoxic effect of cisplatin has become the unpredictable dose-limiting factor in its use as curative as well as palliative therapy. The drug accumulates in highly vascular areas in the cochlea, causing dose-related hair cell loss. The purpose of this study was to assess blood flow-dependent aspects of cisplatin absorption in the cochlea in order to better understand factors that may influence cisplatin-induced ototoxicity. The effect of reduced cochlear blood flow on the ototoxic action of cisplatin was studied in guinea pigs. Before cisplatin administration the cochlear vasculature in each animal was unilaterally pre-constricted, by the application of 2% epinephrine to the round window. A 20-30% reduction in cochlear blood flow, assessed by laser Doppler flowmetry, was maintained before and after intravenous infusion of 0.1% cisplatin. Cisplatin infusion affected cochlear blood flow but not vessel conductivity. The cochlear blood flow decrease, maintained by local epinephrine application to the round window during cisplatin infusion, did not alter the cisplatin-induced hearing loss. In addition, the concentration of free cisplatin in scala tympani perilymph did not differ between epinephrine-treated and non-treated ears. Our results indicate that cisplatin transport into the cochlea is not an energy-dependent process in the lateral wall vasculature.
顺铂耳毒性的个体间差异很大，这已成为其在根治性和姑息性治疗中不可预测的剂量限制因素。该药物在耳蜗的高血管区域蓄积，导致与剂量相关的毛细胞损失。本研究的目的是评估耳蜗中顺铂吸收的血流依赖性方面，以便更好地理解可能影响顺铂诱导耳毒性的因素。在豚鼠中研究了耳蜗血流减少对顺铂耳毒性作用的影响。在给予顺铂之前，通过向圆窗应用2%肾上腺素，对每只动物的耳蜗血管进行单侧预收缩。在静脉输注0.1%顺铂前后，通过激光多普勒血流仪评估，耳蜗血流减少20%-30%。顺铂输注影响耳蜗血流，但不影响血管传导性。在顺铂输注期间通过向圆窗局部应用肾上腺素维持的耳蜗血流减少，并未改变顺铂诱导的听力损失。此外，肾上腺素处理组和未处理组的鼓阶外淋巴中游离顺铂的浓度没有差异。我们的结果表明，顺铂向耳蜗的转运在侧壁血管系统中不是一个能量依赖过程。
