Role of Mannitol in Reducing Postischemic Changes in Distortion‐Product Otoacoustic Emissions (DPOAEs): A Rabbit Model

Abstract

Objectives-The aim of this study was to observe the effects of mannitol, administered topically at the round window (RW), on cochlear blood flow (CBF) and distortion-product otoacoustic emission (DPOAE) after repeated episodes of cochlear ischemia.Methods-Ten young rabbits were used for this study. Reversible ischemic episodes within the cochlea were induced by directly compressing the internal auditory artery (IAA). CBF was measured using a laser-Doppler (LD) probe positioned at the RW niche. DPOAEs were measured at 4, 8, and 12 kHz geometric mean frequency (GMF) using 60 dB sound pressure level (SPL) primary tone stimuli. In five test ears, mannitol was administered topically at the RW for 30 minutes before the IAA compressions. In five control ears, the IAA compressions were undertaken without application of RW medication. Each ear underwent three 5 minute IAA compressions with a 60 minute rest period between compressions.Results-In the control animals, it was observed that a progressive reduction in DPOAE level followed each successive IAA compression at all three test frequencies. The reduction in DPOAE amplitudes was consistently greater at the higher test frequencies. In the test rabbits, the RW administration of mannitol resulted in significantly less reduction in DPOAE level measures after repeated IAA compressions. For example, 30 minutes after reperfusion at 12 kHz GMF, DPOAE levels in the control ears were reduced by 1.5, 6.0, and 16 dB, compared with 1.5, 4.0, and 6.0 dB in the mannitol test ears.Conclusions-Mannitol appears to exert a protective effect on cochlear function after periods of ischemia. The RW appears to be an efficacious route for topical administration of mannitol into the inner ear.

A model of real time monitoring of the cochlear function during an induced local ischemia

“…The level of natural glutathione within the OHCs at the basal cochlea was found to be significantly lower than that at the apical turn, confirming a key role of the glutathionedependent antioxidant system in protection against various factors damaging cochlear function (Sha et al, 2001). Radical scavengers, iron chelators and nitric oxide synthase inhibitors attenuated the damaging effects of ROS following ischemia/reperfusion episodes by enhancing efficacy of the antioxidant system within the cochlea (Morawski et al, 2003c;Tabuchi et al, 1998Tabuchi et al, , 2001a.…”

Ototoxicity caused by topical administration of gentamicin versus tobramycin in rabbits

“…In two rabbits in the gentamicin group (11 and 13), cochlear activity was reduced in all frequencies, according to the third DPOAE measurement. In six rabbits in the tobramycin group (rabbits 6,8,10,12,14,19), cochlear activity was reduced in all frequencies, according to the third DPOAE measurement on day 14 (Table 1). …”

“…The incidence of side effects may even be higher in developing countries where the drugs are generally available over the counter and drug serum levels in patients are not routinely examined to adjust dosing to avoid excessive peak levels that may be associated with a higher risk of ototoxicity. Ototoxic phenomena are associated with factors such as the duration of treatment, the number of treatment courses with aminoglycosides, and the total quantity of the administered drug and the pre-existence or not of hearing impairment [6]. Rybak et al [7] emphasized that the potential for lowering the risk of ototoxicity from aminoglycosides via once-daily aminoglycoside administration was important.…”

Ototoxicity caused by once- and twice-daily administration of amikacin in rabbits

“…Rabbit models have been used in the past in order to investigate hearing impairment after drug administration [11], closed head injury [12] and noise-induced changes in suppression in DPOAEs [13,14].…”

“…Ototoxic phenomena are associated with factors such as the duration of treatment, the number of treatment courses with aminoglycosides and the total quantity of administered drug and the pre-existence or not of hearing impairment [15]. A number of different hypotheses have been proposed to explain the ototoxic effects of aminoglycosides.…”