Alec Salt, PhD, Professor, Otolaryngology-Head & Neck Surgery
Normal inner ear fluids composition is essential to maintain the sensitivity of the ear. We are interested in how these fluids are maintained and regulated under normal and abnormal conditions, and how this affects auditory function.
Local drug delivery to the inner ear has become widely used in the clinic to treat a number of conditions. We study how the applied drugs get into the inner ear, where they spread to, and how long they remain there. Experiments are interpreted by computer simulations of the inner er fluids. This work helps optimize drug delivery protocols so that maximum benefit is achieved.
We also study how the ear responds to very low frequency noise, including infrasound. Wind turbines generate high levels of infrasound which some people find disturbing. We have shown that while you can’t hear infrasound, your ears are detecting and responding to it, and it may affect your health through non-auditory pathways.
Inner Ear Pharmacokinetics
Management of disorders of the ear, such as Meniere’s disease and sudden hearing loss, commonly involves the application of drugs to the inner ear. This is typically accomplished by intratympanic injections of drugs. Quantifying the amount of drug entering the inner ear and where the drugs reach is difficult to measure in humans, so our understanding of these procedures is mostly based on work in animals, in conjunction with computer modeling to scale measures from animals to the human ear. Our research involves development of drug application procedures, cochlear fluids sampling procedures and computer models so that the data can be interpreted quantitatively. We have established how the drugs enter the ear, where they spread to and how long they stay there.
Responses of the Ear to Low Frequency Sounds
Although hearing is insensitive to very low frequency sounds and infrasound, the inner ear is detecting it and converting it to electrical signals. This may be used to help cancel this noise from hearing, in an analogous manner to a noise-canceling headphone in which the noise is first detected and then used to eliminate it from heard sounds. Because the ear is responding to low frequency sounds, it is possible that such noises could affect you in ways that do not involve conscious hearing. Under some conditions, commercial wind turbines generate high levels of very low frequency sound. Some people living near these machines report otologic symptoms (dizziness, nausea, tinnitus), an annoying amplitude modulation of sounds and sleep disturbance. Our projects are investigation the possible mechanisms that underlie such symptoms.
Objective Measures of Cochlear Function
There are many fairly standardized ways to assess how the ear is working using electrical (CAP, ABR, etc) or acoustical (DPOAE, SFOAE, etc) measurements. There are also a wide range of measurements that are less studied but which may be very valuable. In conjunction with our manipulations of the ear, we make a variety of measurements which we correlate with the induced changes. Some of these measures (such as Jeff Lichtenhan’s new ANOW method) give new insights into how the ear is working. We are also developing a number of other measures which may be useful to diagnose pathologies of the ear.
- Alec N. Salt, PhD
- Jeffrey T. Lichtenhan, PhD
- Jared J. Hartsock
- Ruth M. Gill
NIH/NIDCD 5R01DC001368-24 (Alec Salt, PI) 3/1/1991 – 5/312020
“Inner Ear Fluid Interactions”
The goals of this project are to understand mechanisms of cochlear fluid regulation, with an emphasis on the pharmacokinetics of drugs in inner ear fluids. We have developed novel methods to deliver drugs to the ear quantitatively, and to measure their concentration in inner ear fluids through fluids sampling or with ion-selective electrodes. Data are interpreted using mathematical models of solute dispersal in the inner ear fluid spaces based on accurate 3D measurements of inner ear geometry. Current projects are seeking to deliver drugs to the ear more effectively and to establish the pharmacokinetic properties of different drugs in the ear, so that those that re most effective can be selected for clinical use. Alec Salt is the PI of the project.
Salt AN, Hartsock JJ, Piu F, Hou J. Comparison of the pharmacokinetic properties of triamcinolone and dexamethasone for local therapy of the inner ear. Frontiers in Cellular Neuroscience 2019; 13, 347. Salt AN, Plontke SK. Pharmacokinetic principles in the inner ear: Influence of drug properties on intratympanic applications. Hear Res. 2018; 368:28-40.
Salt AN, Hartsock JJ, Piu F, Hou J. Dexamethasone and dexamethasone-phosphate entry into perilymph compared for middle ear applications in guinea pigs. Audiol Neurootol. 2018; 23:245-257
Salt A, Hartsock J, Gill R, Smyth D, Kirk J, Verhoeven K. Perilymph pharmacokinetics of marker applied through a cochlear implant in guinea pigs. PLoS One. 2017 12(8):e0183374.
Salt AN, Hartsock JJ, Gill RM, King E, Kraus FB, Plontke SK. Perilymph pharmacokinetics of locally-applied gentamicin in the guinea pig. Hear Res. 2016 342:101-111.
Salt AN, Hartsock JJ, Gill RM, Piu F, Plontke SK. Perilymph pharmacokinetics of markers and dexamethasone applied and sampled at the lateral semi-circular canal. J Assoc Res Otolaryngol. 2012 13(6): 771–783.
660 S. Euclid Ave.
Campus Box 8115
St.Louis, MO 63110
4560 Clayton Ave.
Rm 2274 (office), 2138 (lab)
St. Louis, MO 63110