[Various aspects of the ototoxic effect of the diuretic ethacrynic acid].
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Biomedical subjects
Publications and source records attributed to I Melichar.
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After i.v. injection of 50 mg/kg ethacrynic acid (EA), potassium concentration in the endolymph (Ke+) measured with K+-specific microelectrodes decreases by 10 mM at the most and endocochlear potential falls to negative values. Potassium concentration in the perilymph (Kp+) generally does not change, but sometimes a transient decrease in Kp+ level of about 0.5 mM was observed, presumably due to the electrogenic effect of the time-related decrease of the endocochlear potential. When anoxia is induced approximately 120 min after EA administration Ke+ slowly decreases. The decrease in Ke+ 50 min after the arrest of ventilation is smaller when compared with the Ke+ anoxic decrease without preceding EA administration. The endocochlear potential, which falls to negative values during anoxia after EA administration, does not return to the zero level as in the case when only anoxia is applied. Similarly, during anoxia, which follows EA administration, the perilymphatic Ke+ concentration increases more slowly than in the case when only anoxia is introduced. It is assumed from the results that EA abolishes activity of the positive electrogenic K+ pump and reduces the passive permeability of the walls of the cochlear duct to the potassium ions.
The endocochlear potential (EP), potassium concentration in the endolymph (Ke+) and in the perilymph (Kp+) were measured in guinea-pigs during anoxia of different duration. Specific K+ double-barrel microelectrodes with liquid ion exchanger were used. The resting K+ concentration in the endolymph was 146.8 +/- 9.2 mM and in the perilymph 3.2 +/- 0.5 mM. The following time course of events was observed in the cochlea during anoxia: 40-50 s after the arrest of ventilation the K+ concentration decreased by 0.1-0.2 mM in the scala vestibuli, which was time related to a rapid fall of EP to negative values. Perilymphatic K+ started to increase in both scalae with a latency of 2-2.5 min, reaching a concentration of about 14 mM 60 min after the arrest of ventilation. The endolymphatic K+ began to decrease after a latency of 2.5-3 min, and 60 min after the arrest of ventilation an 80% concentration (average 112 mM K+) was reached as compared to the initial value. From the comparison of K+ concentration changes with the experimental values of the negative EP, it may be assumed that the negative EP is mainly generated by the K+ gradient between the perilymph and endolymph.
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