Division of Audiology, Department of Clinical Science, Intervention, and Technology Karolinska Institutet, Stockholm.
Department of Surgical Sciences, Uppsala University Hospital, Uppsala University, Uppsala.
Otol Neurotol. 2020 Apr;41(4):545-553. doi: 10.1097/MAO.0000000000002571.
Furosemide alters the permeability of the intrastrial fluid-blood barrier.
The cochlear sensory cells are protected by the blood-perilymph and intrastrial fluid-blood barriers, which hinder substances, including gadolinium-based contrast agents (GdCAs), to enter the endolymphatic space. High-dose furosemide causes transient shift of hearing thresholds and morphological changes in stria vascularis. Furosemide is also known to enhance drug-induced ototoxicity.
Furosemide (400 mg/kg b.w.) was injected i.v. in Balb/C mice (n = 20). Twenty minutes later, the GdCA gadobutrol, gadopentetic acid, or gadoteric acid was injected i.v. The distribution of GdCA to the perilymphatic and endolymphatic spaces was studied with MRI (9.4 T) for 250 minutes.
The perilymphatic and endolymphatic spaces were signal-enhanced in all animals. Gadopentetic acid and gadoteric acid yielded similar signal enhancement in all three scalae, while gadobutrol yielded significantly higher enhancement in scala tympani than scala media (p = 0.043) and scala vestibuli (p = 0.043). The signal enhancement reached a plateau but did not decrease during the time of observation.
Treatment with a high dose of furosemide before injection of a GdCA resulted in enhancement of the MRI signal in the endolymphatic space as well as the perilymphatic space, which supports our hypothesis that furosemide alters the permeability of the intrastrial fluid-blood barrier.
速尿改变了内耳蜗液-血屏障的通透性。
耳蜗感觉细胞受到血-迷路和内耳蜗液-血屏障的保护，这些屏障阻止包括钆基造影剂（GdCA）在内的物质进入内淋巴间隙。大剂量速尿可导致听力阈值暂时改变和血管纹形态变化。速尿也已知可增强药物引起的耳毒性。
速尿（400mg/kg b.w.）静脉注射 Balb/C 小鼠（n=20）。20 分钟后，静脉注射 GdCA 钆布醇、钆喷替酸或钆特酸。使用 9.4T MRI 研究 GdCA 向外淋巴和内淋巴间隙的分布 250 分钟。
所有动物的外淋巴和内淋巴间隙均有信号增强。钆喷替酸和钆特酸在所有三个耳蜗腔中均产生相似的信号增强，而钆布醇在鼓阶中的信号增强明显高于中阶（p=0.043）和前庭阶（p=0.043）。信号增强达到平台期，但在观察期间没有下降。
在注射 GdCA 之前用大剂量速尿治疗可导致内淋巴间隙和外淋巴间隙的 MRI 信号增强，支持我们的假设，即速尿改变了内耳蜗液-血屏障的通透性。
