Erik Berninger, Hörselkliniken/audiologen, Huddinge Universitetssjukhus AB,
141 86 Stockholm
Erik Berninger försvarade sin avhandling den 8 september 2000.
(erik.berninger@karolinska.se)

Quinine has been used for centuries and is still recommended for the treatment of severe falciparum malaria and non-severe chloroquine-resistant malaria. Among its side effects is the concentration-dependent and reversible cochlear hearing loss. A non-linear pharmacological model reliably described the contrantration-effect relationship in healthy and normal hearing volunteers with oral and intravenous administration of the drug. Free (non-protein bound) intravenous plasma concentrations that were 10-15% total concentrations gave i similar hearing impairment. Computer-controlled intravenous infusion was used to rapidly achieve and then maintain a desired target plasma concentration of quinine, thus allowing detailed audiologic testing. Auditory sensitivity,frequenc selectivity, and various forms of otoacoustic emissions (OAEs) were reduced by quinine. The reversible and flat-frequency hearing loss was characterized by complete loudness recruitment, even at the most pronounced pure-tone threshold (PTT) shift (46 dB). Quinine is a useful model substance for the study of OAEs, as it is hypothesized to interfere with the normal function of the cochlear outer hair cells. The most vulnerable formof OAE was spontaneous OAE (SOAE). They were abolished at the recorder hearing threshold which ranged from 8 to 24 dB. The SOAEs revealed complete recovery. A distinct 1:1 relationship existed between quinine-induced shifts in the detection threshold of click-evoked OAE (COAE) and its corresponding psychoacoustical treshold, which indicates a reversible alteration in the micromechanically active cochlea. The slope of the COAE growth function increased with increasing hearing threshold shift, from 0.35 to a maximum of 1.1 dB/dB, thus reflecting a recruitment-like behaviour. The mean quinine-induced shift in the 2f1-f2 acoustic distortion product OAE (DPOAE) increased continuously with decreasing equilevel primaries (f2/f1 = 1.22). For example, at the primary tone level 45 dBSPL, the mean DPOAE shift was half the mean hearing threshold shift. No correlation was found between quinine-induced shift in DPOAE and PTT. Highly vulnerable SOAEs and COAEs, in combination with the less vulnerable DPOAEs, fit into a recently proposed taxonomic classification for OAEs. Quinine is a useful model substance for reversible inducing complete loudness recruitment in humans as it acts specifically on some parts of the hearing function. Its mechanism of action on the molecular level is likely to reveal further information on the physiology of hearing.

Key words: cochlear function, hearing loss, inner ear,otoacoustic emissions, quinine, pharmacokinetics, pharmacodynamics.

ISBN 91-628-4272-2