The ototoxicity of topically applied povidone-iodine preparations.
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Biomedical subjects
Publications and source records attributed to T Morizono.
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Chinchillas were anesthetized with ketamine (40 mg/kg i.m.) and endocochlear potential (EP) and potassium concentration in endolymph (Ke+) were determined in control animals and in animals injected with various doses of furosemide (25, 50 or 100 mg/kg i.v.) by means of microelectrodes inserted into scala media. Control EP and Ke+ in the chinchilla were 81.3 +/- 3.8 mV and 158.5 +/- 3.2 mequiv./l, respectively. Following injection of furosemide, a dose-related fall in EP and Ke+ was observed. However, the EP declined much more rapidly than the Ke+, and recovered more quickly than the latter. The recovery of Ke+ tended to lag behind the EP recovery. The debate over whether potassium transport into endolymph and endocochlear potential generation are related or independent events is discussed in the light of recent literature and the present study.
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Guinea pigs and chinchillas were studied for EP and potassium concentrations in scala media and scala tympani using potassium-sensitive microelectrodes. Response of EP to 3 min anoxia was strikingly different in these two species. On the other hand, the resting values for EP and potassium concentrations in endolymph and perilymph were not significantly different. These findings suggest that the different response to anoxia in these two species is due to differences in permeability of the cochlear partitions to the ions.
The ototoxicity of antibiotics given either systemically or topically has been recently recognized. However, the ototoxicity of topically applied alcohols and other solvents used as vehicles for drugs has not been well recognized. One of the most common solvents, propylene glycol, was chosen for this study, and this agent in various concentrations was instilled into the middle ear of guinea pigs and chinchillas for various periods of time. Its effect on the function of the cochlea was studied as well as the histopathologic changes in the temporal bones. Deterioration of the cochlear microphonics and the endocochlear direct current potential was found. A 10 per cent solution applied for six days caused a reduction in the cochlear microphonics. Fifty per cent or stronger solution always caused a reduction in the cochlear microphonics. The deterioration in the cochlear microphonics persisted one month. Dose related changes in the endocochlear potential were noted. Morphologic changes were severe and included granulation tissue in the middle ear and destruction and ossification of the auditory bulla and bony cochlea. Propylene glycol should not be used in the ear that has a perforation of the tympanic membrane.
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This study was done to determine the comparative elimination kinetics of furosemide from chinchilla perilymph and serum, and to correlate perilymph concentration with changes in endocochlear potential. The elimination kinetics of furosemide (FU) were determined in sera and perilymph obtained from chinchillas injected with 100 mg/kg i.v. of FU. Concentrations of FU exhibited a linear decay pattern in serum and perilymph over the initial 60 minutes. The rate of decline of furosemide levels in perilymph was about four times slower than the rate of fall in serum. Chronic treatment (25 mg/kg i.p. every 12 hours) did not appear to influence the level of drug at 60 minutes after a dose of FU (100 mg/kg IV). Chinchillas were also studied following doses of FU ranging from 25--200 mg/kg i.v. to see the effect on endocochlear potential (EP). A positive correlation was found between FU dosage, the maximum millivolt reduction of EP and the time to initiation of recovery of EP. The perilymph concentration of furosemide when the EP began to recover was 5 microgram/ml (1.5 x 10(-5) M). Knowledge of furosemide kinetics may ultimately be applied to prevent ototoxicity in patients.
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The ototoxicity of chloramphenicol ear drops was studied in guinea-pigs. The ear drops consisted of chloramphenicol sodium succinate in propylene glycol; hence the ototoxicity of each chemical was also studied. The diluted chemicals were instilled in the middle ear cavity; thus clinical conditions were simulated, and the cochlear microphonic responses from the electrode on the round window of the cochlea were monitored as an indication of the hair cell function. Our experiment revealed that propylene glycol at the concentration of 10% or more caused irreversible deafness. Chloramphenicol sodium succinate in a concentration of 5% or more in Ringer's solution also caused irreversible deafness. It is recommended that propylene glycol should not be used in the ear drops as a solvent of the drug. Chloramphenicol at higher concentrations is not recommended for use in the middle ear cavity.
By using an electrical impedance plethysmorgraph and a pressure applicator to a rabbit's earlobe artery, it became possible to monitor the blood pressure for periods of several months. A study of the correlations of the blood pressure from carotid and ear was also made at varied blood pressures under different conditions which showed excellent correlations. This method could effectively replace the encannulation technique for monitoring rabbit's blood pressure in chronic experiments.
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The ototoxicity of an otic drop preparation containing 2% acetic acid and 3% propylene glycol (VoSol, Denver Chemical Co., Humacao, PR) was investigated according to measurements of endocochlear potential (EP) and inner ear fluid pH. The application of this preparation to the round window membrane for 30 minutes caused a depression in EP from 80.5 +/- 2.5 mV (mean +/- SD; n = 6) to 11.7 +/- 7.7 mV, and lowered inner ear fluid pH from 7.55 +/- 0.09 to 5.06 +/- 0.19 (n = 6) in perilymph and from 7.52 +/- 0.07 to 5.88 +/- 0.63 (n = 6) in endolymph. Two percent acetic acid produced similar changes after 30 minutes: EP was reduced from 83.0 +/- 2.2 mV to 34.0 +/- 2.9 mV and endolymphatic pH from 7.49 +/- 0.04 to 6.83 +/- 0.21 (n = 4). However, the application of artificial perilymph of pH 4 titrated with HCl induced no significant changes in either EP or endolymphatic pH. We suggest that the mechanisms of ototoxicity in the otic drop preparation are Na+ and K+-ATPase inhibition, and that such inhibition is due to the intracellular acidification of strial cells resulting from the penetration of acetic acid across the cell membrane, and to the direct and synergistic actions of propylene glycol.
The ototoxicity of the corticosteroid triamcinolone diacetate was investigated using the compound action potential (CAP) of the auditory nerve as a parameter when the drug was applied to the middle ear cavity of the chinchilla. Comparison with the contralateral ear, instilled with Ringer's solution, demonstrated no significant difference in the threshold, amplitude, and latency of the CAP responses at the overall frequencies tested. In addition, the side difference of the CAP threshold in individual animals showed that this corticosteroid did not induce cochlear dysfunction in any case.
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