Lipopolysaccharide decreases cochlear blood flow dose dependently in a guinea pig animal model via TNF signaling

Abstract

Objective: To evaluate the effect of Lipopolysaccharide (LPS), a bacterial endotoxin on cochlear microcirculation, and its mode of action. Methods: Twenty-five Dunkin-Hartley guinea pigs were divided into five groups of five animals each. After surgical preparation, cochlear microcirculation was quantified by in vivo fluorescence microscopy. Placebo or LPS (1 mg, 10 µg, and 100 ng) was applied topically, and microcirculation was measured before and twice after application. A fifth group was pretreated with etanercept, a tumor necrosis factor (TNF) antagonist, and afterward the lowest LPS concentrations that yielded significant results (10 µg) were applied. Results: In the groups that had been treated with 1 mg and 10 µg LPS, a significant drop in cochlear microcirculation was observed after 30 (.791 ±.089 Arbitrary Units (AU), compared to baseline, and.888 ±.071AU) and 60 (.756 ±.101 AU and.817 ±.124 AU, respectively) minutes. The groups that had been treated with 100 ng LPS and that had been pretreated with etanercept showed no significant change in cochlear blood flow compared to placebo. Conclusion: Lipopolysaccharide shows a dose-dependent effect on cochlear microcirculation; this effect can already be observed after 30 min. Pretreatment with etanercept can abrogate this effect, indicating that TNF mediates the effect of LPS on cochlear microcirculation.