BackgroundThe efficiency of cochlear implants (CIs) is affected by postoperative connective tissue growth around the electrode array. This tissue formation is thought to be the cause behind post-operative increases in impedance. Dexamethasone (DEX) eluting CIs may reduce fibrous tissue growth around the electrode array subsequently moderating elevations in impedance of the electrode contacts.MethodsFor this study, DEX was incorporated into the silicone of the CI electrode arrays at 1% and 10% (w/w) concentration. Electrodes prepared by the same process but without dexamethasone served as controls. All electrodes were implanted into guinea pig cochleae though the round window membrane approach. Potential additive or synergistic effects of electrical stimulation (60 minutes) were investigated by measuring impedances before and after stimulation (days 0, 7, 28, 56 and 91). Acoustically evoked auditory brainstem responses were recorded before and after CI insertion as well as on experimental days 7, 28, 56, and 91. Additionally, histology performed on epoxy embedded samples enabled measurement of the area of scala tympani occupied with fibrous tissue.ResultsIn all experimental groups, the highest levels of fibrous tissue were detected in the basal region of the cochlea in vicinity to the round window niche. Both DEX concentrations, 10% and 1% (w/w), significantly reduced fibrosis around the electrode array of the CI. Following 3 months of implantation impedance levels in both DEX-eluting groups were significantly lower compared to the control group, the 10% group producing a greater effect. The same effects were observed before and after electrical stimulation.ConclusionTo our knowledge, this is the first study to demonstrate a correlation between the extent of new tissue growth around the electrode and impedance changes after cochlear implantation. We conclude that DEX-eluting CIs are a means to reduce this tissue reaction and improve the functional benefits of the implant by attenuating electrode impedance.

Interleukin-1 beta (IL-1 beta) has recently been shown to reduce the severity of experimental gastroduodenal damage and to inhibit acid secretion in the pylorus-ligated rat. In the present study, the effects of IL-1 beta on pentagastrin-stimulated acid secretion were compared with those of two other cytokines, namely IL-1 alpha and tumor necrosis factor (TNF) alpha. Also, the effects of IL-1 beta on gastric acid secretion stimulated by bethanechol or histamine were assessed. Anesthetized rats were pretreated intravenously with one of the cytokines, at doses in the 0.1-5 micrograms/kg range, 30 min before starting an intravenous infusion of pentagastrin. TNF alpha failed to significantly affect acid secretion, whereas IL-1 alpha and IL-1 beta exhibited significant inhibitory effects. For example, at a dose of 5 micrograms/kg, IL-1 alpha and IL-1 beta reduced acid secretion by 33 and 80%, respectively. The inhibitory effects of IL-1 beta on acid secretion could be completely inhibited by preincubation with an antibody directed against IL-1 beta but not by pretreatment with indomethacin (5 mg/kg sc) or by bilateral vagotomy. If acid secretion was stimulated by intravenous infusions of histamine or bethanechol, neither IL-1 beta nor TNF alpha produced significant inhibitory effects. Inhibition of acid secretion by IL-1 was also observed when the IL-1 was administered subsequent to stimulation by pentagastrin administration. These results demonstrate that IL-1 beta is an extremely potent inhibitor of acid secretion stimulated by pentagastrin but not that stimulated by histamine or bethanechol, through a mechanism that is at least in part independent of the vagus nerve and of prostaglandin synthesis. IL-1 alpha is less potent as an inhibitor of gastric acid secretion, whereas TNF appears to be inactive. Because pentagastrin-stimulated acid secretion could be completely inhibited by a histamine H2-receptor antagonist (cimetidine) and because IL-1 had no effect on histamine-stimulated acid secretion, it is possible that IL-1 exerts its antisecretory actions by inhibiting pentagastrin-stimulated histamine release.

No abstract

No abstract