Direct Entry of Gadolinium into the Vestibule Following Intratympanic Applications in Guinea Pigs and the Influence of Cochlear Implantation

Abstract

Although intratympanic (IT) administration of drugs has gained wide clinical acceptance, the distribution of drugs in the inner ear following IT administration is not well established. Gadolinium (Gd) has been previously used as a marker in conjunction with magnetic resonance imaging (MRI) to visualize distribution in inner ear fluids in a qualitative manner. In the present study, we applied gadolinium chelated with diethylenetriamine penta-acetic acid (Gd-DTPA) to the round window niche of 12 guinea pigs using Seprapack TM (carboxlmethylcellulose--hyaluronic acid) pledgets which stabilized the fluid volume in the round window niche. Gd-DTPA distribution was monitored sequentially with time following application. Distribution in normal, unperforated ears was compared with ears that had undergone a cochleostomy in the basal turn of scala tympani and implantation with a silastic electrode. Results were quantified using image analysis software. In all animals, Gd-DTPA was seen in the lower basal scala tympani (ST), scala vestibuli (SV), and throughout the vestibule and semi-circular canals by 1 h after application. Although Gd-DTPA levels in ST were higher than those in the vestibule in a few ears, the majority showed higher Gd-DTPA levels in the vestibule than ST at both early and later time points. Quantitative computer simulations of the experiment, taking into account the larger volume of the vestibule compared to scala tympani, suggest most Gd-DTPA (up to 90%) entered the vestibule directly in the vicinity of the stapes rather than indirectly through the round window membrane and ST. Gd-DTPA levels were minimally affected by the implantation procedure after 1 h. Gd-DTPA levels in the basal turn of scala tympani were lower in implanted animals, but the difference compared to non-implanted ears did not reach statistical significance.

Effect of Both Local and Systemically Administered Dexamethasone on Long-Term Hearing and Tissue Response in a Guinea Pig Model of Cochlear Implantation

“…Diffusion is a passive process, largely due to the slow longitudinal flow of perilymph along the cochlea [Salt and Plontke, 2009]. The distribution of a drug already present in the scala tympani is not changed by cochlear implantation, as observed in an MRI study where gadolinium distribution was evaluated [King et al, 2011;Yamazaki et al, 2012]. We found in the present study that the long waiting times required to afford protection from local delivery could not be shortened by increasing the concentration of drug applied to the inner ear.…”

Selective Window Application of Gentamicin Dexamethasone in Meniere's Disease

“…Different drugs had different results [15,16] . It was reported that application of gentamicin to oval window caused more vestibulotoxicity and hearing loss in Gunea pigs [17] .…”

“…Selective absorption has been confirmed by a number of studies. King et al [16] estimated that the rate of gadolinium absorption in the region of stapes was more than 90%. Salt et al [15] showed that trimethylphenylammonium (TMPA) marker was absorbed at a rate of 65% from the round window.…”

Diverse Patterns of Perilymphatic Space Enhancement in the Rat Inner Ear after Intratympanic Injection of Two Different Types of Gadolinium: A 9.4-Tesla Magnetic Resonance Study

“…However, most previous studies have only used one kind of Gd [King et al, 2011;Zou et al, 2010a, b]. Considering that the pattern of enhancement can vary significantly between different contrast agents and between body parts [Anzalone et al, 2013;Kramer et al, 2013;Morelli et al, 2012], the use of different contrast agents in the inner ear may lead to significantly different patterns of enhancement.…”