Ethacrynic acid rapidly and selectively abolishes blood flow in vessels supplying the lateral wall of the cochlea.
The mechanisms underlying the ototoxicity of ethacrynic acid (EA) are not fully understood. Previous studies have focused on morphologic and enzymatic changes in the stria vascularis. The current experiment shows that one of the earliest effects of EA is ischemia, resulting from impaired blood flow in vessels supplying the lateral wall of the cochlea. Inner ear microcirculation, endocochlear potentials, compound action potentials (CAP), cochlear microphonics (CM) and summating potentials (SP) were monitored over time in chinchillas following a single injection of EA (40 mg/kg i.v.). At all times after EA injection, blood vessels supplying the spiral lamina, modiolus, and vestibular end organs appeared normal. In contrast, lateral wall (spiral ligament and stria vascularis) vessels were poorly stained with eosin 2 min after EA injection, and devoid of red blood cells at 30 min post EA. Decline, but not recovery, of CAP, CM and SP followed the microcirculation changes in the lateral wall. Reperfusion was delayed in stria vascularis arterioles relative to other lateral wall vessels. The ischemia-reperfusion caused by EA would be expected to generate large quantities of free radicals, which may trigger or contribute to the cellular, enzymatic, and functional pathologies that have been described in detail previously.
Ding
Dalian
D
Center for Hearing and Deafness, 215 Parker Hall, University at Buffalo, NY 14214, USA.
McFadden
Sandra L
SL
Woo
Jenifer M
JM
Salvi
Richard J
RJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D002682:Chinchilla; D003051:Cochlea / Q000098:blood supply* / Q000502:physiology; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology*; D007758:Ear, Inner / Q000098:blood supply; D004594:Electrophysiology; D004976:Ethacrynic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007511:Ischemia / Q000139:chemically induced; D008833:Microcirculation / Q000187:drug effects; D009925:Organ of Corti / Q000187:drug effects / Q000473:pathology; D012039:Regional Blood Flow / Q000187:drug effects; D015424:Reperfusion; D013316:Stria Vascularis / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D013997:Time Factors; D014722:Vestibule, Labyrinth / Q000098:blood supply
D004232:Diuretics; D004976:Ethacrynic Acid