Endotoxin permeability through the round window

The permeability of the round window membrane to Salmonella typhimurium derived endotoxin was examined using a total of 17 chinchillas. One mg of endotoxin was instilled into the tympanic cavity via the superior bulla. Endotoxin activity in middle ear effusions (MEEs), perilymph (both inoculated and non-inoculated side), and sera was determined by Limulus lysate assay after 12, 24, 48, 72, and 120 h following endotoxin instillation. Endotoxin was detected in perilymph on the inoculated side by 12 h after endotoxin instillation and persisted for 5 days during the present measurement period. Endotoxin level peaked at 24-48 h post-instillation, and steadily declined afterwards. This result suggests that the maximum penetration occurred during the active inflammatory stage. Histologic investigation revealed marked pathological changes in the inner ear, including bleeding and inflammatory cell recruitment, mostly in the perilymphatic spaces (e.g. scalae tympani and vestibuli, spiral ligament), strial swelling, and sensory cell degeneration. These results suggest that endotoxin, when introduced into the middle ear, can permeate through the round window membrane and can cause inner ear tissue damage in this animal model.