Pernilla Videhult Pierre1, Jesper Edvardsson Rasmussen2, Sahar Nikkhou Aski3, Peter Damberg4,5, Göran Laurell2. 1. Division of Audiology, Department of Clinical Science, Intervention, and Technology Karolinska Institutet, Stockholm. 2. Department of Surgical Sciences, Uppsala University Hospital, Uppsala University, Uppsala. 3. Medical Radiation Physics and Nuclear Medicine. 4. Karolinska Experimental Research and Imaging Centre, Karolinska University Hospital. 5. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Abstract
HYPOTHESIS: Furosemide alters the permeability of the intrastrial fluid-blood barrier. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
HYPOTHESIS: Furosemide alters the permeability of the intrastrial fluid-blood barrier. BACKGROUND: 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. METHODS:Furosemide (400 mg/kg b.w.) was injected i.v. in Balb/C mice (n = 20). Twenty minutes later, the GdCAgadobutrol, 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. RESULTS: 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. CONCLUSION: 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.