Differential actions of isoflurane and ketamine-based anaesthetics on cochlear function in the mouse

Abstract

Isoflurane is a volatile inhaled anaesthetic widely used in animal research, with particular utility for hearing research. Isoflurane has been shown to blunt hearing sensitivity compared with the awake state, but little is known about how isoflurane compares with other anaesthetics with regard to hair cell transduction and auditory neurotransmission. The current study was undertaken in C57Bl/6J and C129/SvEv strains of mice to determine whether isoflurane anaesthesia affects hearing function relative to ketamine-based anaesthesia. Cochlear function and central auditory transmission were assessed using auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE), comparing thresholds and input/output functions over time, for isoflurane vs. ketamine/xylazine/acepromazine anaesthesia. ABR thresholds at the most sensitive region of hearing (16 kHz) were initially higher under isoflurane anaesthesia. This reduced hearing sensitivity worsened over the 1 h study period, and also became evident with broadband click stimulus. Ketamine anaesthesia provided stable ABR thresholds. Although the growth functions were unchanged over time for both anaesthetics, the slopes under isoflurane anaesthesia were significantly less. Cubic (2f1–f2) DPOAE thresholds and growth functions were initially similar for both anaesthetics. After 60 min, DPOAE thresholds increased for both groups, but this effect was significantly greater with ketamine anaesthesia. The isoflurane-mediated increase in ABR thresholds over time is attributable to action on cochlear nerve activation, evident as a right-shift in the P1-N1 input/output function compared to K/X/A. The ketamine-based anaesthetic produced stable ABR thresholds and gain over time, despite a right-shift in the outer hair cell – mediated DPOAE input/output function.

A comparison of auditory brainstem responses across diving bird species

“…However, it is possible that species or individuals could vary in their response to the anesthesia. Isoflurane, which was used for all birds in this study, has been shown to elevate thresholds compared to a ketamine/xylazine combination in rats and mice, with a reduction in sensitivity over the duration of anesthesia (Cederholm et al 2012; Ruebhausen et al 2012). Deep anesthesia with ketamine, nembutal and halothane reduced or eliminated both cochlear action potentials and distortion products in starlings and chickens (Kettembeil et al 1995).…”

Mutation of the ATP-gated P2X 2 receptor leads to progressive hearing loss and increased susceptibility to noise

“…P2RX2-null and background strain C57BL/6J WT mice were born and raised either in a quiet environmental chamber or in an environmental chamber with a continuous noise level of 75 dB SPL, 8-16 kHz. Assessments of hearing function were performed using established protocols (39). Mid-modiolar cochlear cyrosections from the quiet-chamber 17-mo old P2RX2-null and WT mice were examined by immunofluorescence confocal microscopy as described previously (40).…”

Age-related shifts in distortion product otoacoustic emissions peak-ratios and amplitude modulation spectra

“…Animals were anaesthetized initially by inhaling 4 % isoflurane in an induction chamber. They were then transferred to the manifold and maintained with 1.8 % isoflurane (for young rats) or 1.5 % isoflurane (for aged rats) on a water circulated warming blanket (Kent Scientific) set to 37°C during the whole recording session of 30–60 mins (Cederholm, Froud et al 2012). Stimulus presentation and DPOAE recordings were performed using BioSig (Tucker Davis Technologies, TDT) in the acoustic chamber.…”