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Biomedical subjects

R Thalmann

Publications and source records attributed to R Thalmann.

At least 73 records · Page 4Linked to original sources
PubMed1982

Minimal concentrations of metabolic substrates capable of supporting cochlear potentials.

The objective of this study was to determine the capability of glucose analogues, as well as lactate and pyruvate, to maintain the endolymphatic potential and the cochlear microphonics. In addition, the minimum concentration at which different substrates (including D-glucose) were able to sustain the potentials ("critical' concentration) was determined. Synthetic blood containing various substrates at different concentrations was perfused via the anterior inferior cerebellar artery. The critical concentration for D-glucose was found to be 15 mg% (0.83 mM). L-Glucose, galactose and fructose were not able to support the potentials at concentrations as high as 200 mg%. On the other hand, mannose was capable of supporting the potentials; however, the critical concentration (50 mg% or 2.8 mM) was substantially higher than that of D-glucose. Both lactate and pyruvate could support the potentials, but the critical concentrations (8.5 mM and 6.5 mM, respectively) were markedly higher than in the case of glucose, even when the difference of carbon equivalents was taken into consideration. The data are discussed in the context of the intermediary metabolism and possible carrier systems of the stria vascularis.

Action Potentials↗
PubMed1982

Amino acid profiles in inner ear fluids and cerebrospinal fluid.

The levels of 19 amino acids in utricular endolymph, vestibular and cochlear perilymph, and cerebrospinal fluid of guinea pigs were determined using gradient elution reverse phase high performance liquid chromatography of the o-phthaldialdehyde-ethanethiol adducts with fluorescence detection. Aspartate and glutamate were significantly higher in endolymph than in perilymph, in agreement with earlier results on cochlear fluids based on enzymatic fluorometric techniques. All other amino acids tested were significantly lower in the endolymph, in most cases by an order of magnitude. Vestibular perilymph and perilymph of scala vestibuli are virtually identical. Amino acid levels were all higher in perilymph of scala vestibuli than in cerebrospinal fluid; two by an order of magnitude. All differences were statistically significant, with the exception of aspartate. Amino acid levels in perilymph of scala tympani were highly variable dependent upon sampling technique, and no definite values are therefore presented. Comparisons with results from other laboratories, technical pitfalls, and possible implications and interpretations of the results are presented.

Amino Acids↗
PubMed1982

Arguments against a mediating role of the adenylate cyclase--cyclic AMP system in the ototoxic action of loop diuretics.

Previous studies in our laboratory have indicated that adenylate cyclase of the stria vascularis is strongly inhibited in vitro by ethacrynic acid and furosemide. In order to test whether the in vitro effects upon the enzyme are also present under in vivo conditions, ethacrynic acid was perfused perilymphatically for 15 min and 20 min at a concentration of 10(-3) M. Cyclic AMP of the stria vascularis was reduced by 27% and 34%, respectively, but ATP also declined significantly, suggesting unspecific effects. When ethacrynic acid was applied intravenously at a dosage of 50 mg/kg, and the endolymphatic potential allowed to decline to -10mV, no significant changes in cyclic AMP and ATP were seen. The absence of effects upon cyclic AMP in the early stage of systemic intoxication with ethacrynic acid is strong evidence against a mediating role of adenylate cyclase in the ototoxic action of ethacrynic acid. When a bolus of 3 x 10(-2) M furosemide was applied intra-arterially the endolymphatic potential declined at the exceedingly rapid rate of about 10 mV/sec, strongly suggesting that the action of the drug takes place in the vicinity of the capillaries of the stria vascularis. In view of the proposition that adenylate cyclase appears to be located primarily at eh luminal aspect of the stria vascularis, this constitutes further evidence against a role of the enzyme in the mediation of the specific ototoxic effects of loop diuretics. Other recent evidence against a mediatory role of the adenylate cyclase--cyclic AMP system is discussed.

Adenosine Triphosphate↗
PubMed1981

Changes in cation contents of stria vascularis with ouabain and potassium-free perfusion.

Perfusion of the perilymphatic space of guinea pig cochleae with K-free medium leads to a gradual decline of the endocochlear potential (EP) over 30-50 min to a negative value (mean: -12 mV). The input resistance of scala media does not decrease during this time. The ATP and K content of the stria vascularis are reduced by similar amounts (26 and 34%, respectively) during this period. Perfusion of 1 mM ouabain produces a different pattern of response: strial ATP remains normal while strial K content is strongly reduced (by 77%). Strial Na rises in a complementary way to the K loss. These results demonstrate that a reduction of the K concentration of the perilymph leads to an inhibition of the generator of the positive component of the EP rather than to a general increase of cochlear duct membrane conductance. In addition, they suggest, in concert with other considerations (such as the slower rate of decline of the EP during K-free vascular perfusion (Wada, J., Kambayashi, J., Marcus, D.C. and Thalmann, R (1979): Arch. Otorhinolaryngol. 225, 79-81)), that the mode of action may be different from that of ouabain. In spite of the lack of teleological support, we offer the hypothesis that the strial generator of the EP may primarily utilize K from perilymph and that vascular K may not have access to the generator.

Adenosine Triphosphate↗
PubMed1981

Specificity of action of vanadate to the organ of corti.

Although vanadate strongly inhibits Na/K-ATPase activity of the stria vascularis in vitro, it initially causes no depression of the ouabain-sensitive endocochlear potential (EP) when perfused perilymphatically or via the vasculature. However, when the perilymph of scala tympani is replaced with artificial media containing 0.1 to 1 mM vanadate, there is a large (about 17 mV) increase in the EP of the second cochlear turn. Further experiments showed that the cochlear microphonics declined during the time in which the EP increased, and that the response of these two potentials to vanadate is greater in the second turn than in the first. Injection of 50 n1 of 1 mM vanadate (in artificial endolymph) into the endolymphatic space of the second turn caused no increase in the EP. These results support the notion that the early effects of vanadate are on the contra-luminal membranes of cells of the organ of Corti rather than on the stria vascularis. By superimposing anoxia or furosemide (i.v.) upon vanadate intoxication, we determined that the initial increase of the compound EP due to vanadate alone was due to a reduction in magnitude of the negative component of the EP. It is argued that of the three prevalent theories concerning the generation of the negative EP, the data tend to support the hypothesis that the intracellular potential of the hair cells gives rise to the negative EP.

Adenosine Triphosphatases↗
PubMed1981

Steep gradients of amino acids between cochlear endolymph and perilymph.

Levels of 19 free amino acids in cochlear endolymph and perilymph of scala vestibuli of the guinea pig were determined using reverse phase high performance liquid chromatography (HPLC) of the o-phthaldialdehyde-ethanethiol derivatives with fluorescence detection. Aspartate and glutamate were found to be significantly higher in endolymph than in perilymph, confirming results from another study using a different analytical method. The remaining 17 amino acids were significantly lower in the endolymph, in many cases by an order of magnitude. The data are compared with results on utricular endolymph and vestibular perilymph obtained by HPLC in another study from our laboratory. Possible implications and interpretations of the results are discussed.

Amino Acids↗
PubMed1980

Stimulus-induced release of endogenous amino acids from skins containing the lateral-line organ in Xenopus laevis.

The release of endogenous amino acids from skins of Xenopus laevis was studied by comparing the effects of pulsatile water motion on the efflux of glutamate and aspartate from isolated skins with and without lateral-line stitches. The stimulated efflux of glutamate from stitch skins was significantly greater than its stimulated efflux from non-stitch skins (p < 0.01). The results for aspartate were less clear cut. Although the source and mechanisms underlying the greater stimulated efflux from stitch skins remain to be determined, the results demonstrate that differences can be detected between stitch and non-stitch skins under stimulus conditions which should induce release of the afferent transmitter substance(s).

Animals↗
PubMed1980

Organ of Corti-specific polypeptides: OCP-I and OCP-II.

Two polypeptides, OCP-I and OCP-II, specific to the organ of Corti of the quinea pig and the rate, were detected by two-dimensional polyacrylamide gel electrophoresis. They were neither present in other inner ear structures, nor in other organs tested. The two polypeptides constitute a substantial portion of the total protein of the organ of Corti. Both inner and outer layer of the organ of Corti contained approximately equal amounts of OCP-I and OCP-II. The molecular weights of OCP-I and OCP-II are 37,000 and 22,500 daltons, respectively. The corresponding pI values are 4.9 and 5.1, respectively. in addition, actin and tubulin were detected in both layers of the organ of Corti.

Animals↗
PubMed1979

Maintenance of cochlear function with artificial oxygen carriers.

By means of vascular perfusion via the anterior inferior cerebellar artery with a blood substitute containing the perfluorochemical FC 47 as oxygen carrier, it is possible to maintain normal or near normal levels of the cochlear microphonics and the endolymphatic potential of the guinea pig for perios of 90 min, or longer. Following 60 min. of perfusion with artificial blood, the levels of ATP and 5' AMP in the stria vascularis and the organ of Corti are comparable to those of nonperfused control animals maintained at optimal metabolic conditions. Following the same period of perfusion, the appearance of the organ of Corti is normal, but small vacuoles, presumably deposits of FC 47, are visible in the marginal cells of the stria vascularis. Preliminary experiments concerning the survival time and the revival time of the cochlear potentials, as well as the response to furosemide, ouabain, and mersalyl are presented to illustrate the value of this method in elucidating various biochemical and pharmacological problems of the cochlea.

Adenosine Monophosphate↗
PubMed1979

Vascular perfusion of the cochlea: effect of potassium-free and rubidium-substituted media.

By means of vascular perfusion of the cochlea with K+-free synthetic blood, it is possible to maintain the endocochlear potential (EP) at normal or supernormal levels for periods of 20-42 min. The subsequent decline of the EP is comparatively slow. This is in contrast to the immediate onset and rapid decline of the EP during perilymphatic perfusion with K+-free media. Possible implications of these data concerning the mode of generation of the EP are briefly discussed. It is further shown, that synthetic blood, in which K+ is replaced by Rb+, maintains the EP at normal or near normal levels for 2 h.

Cochlea↗
PubMed1979

Adenine nucleotides of the stria vascularis.

The levels of the adenine nucleotides ATP, ADP, and AMP in the stria vascularis were measured under normal conditions, and following various durations of ischemia. The concentrations of these compounds were used for the calculation of the adenylate energy charge, the energy status and the phosphorylation state of the stria. Following 10 min of ischemia the adenylate energy charge had decreased three fold, the energy status seven fold and the phosphorylation state 14 fold. To study the potential for recovery of strial function following various brief and prolonged ischemic intervals, a method for the perfusion of the ear via the anterior inferior cerebellar artery was developed. For various reasons it was found advantageous to use "artifical blood" as perfusate, relying upon fluorocarbons as oxygen carriers. The endolymphatic potential was used as electrical indicator of strial function. Recovery of the endolymphatic potential following brief periods of ischemia was paralleled by a corresponding increase of the ATP levels and a drastic decrease of the AMP levels of the stria vascularis. Preliminary results on the effects of substrate-free perfusion are presented.

Adenine Nucleotides↗
PubMed1978

Respiratory quotient of stria vascularis of guinea pig in vitro.

The respiratory quotient of the stria vascularis was measured in vitro by means of Cartesian diver microgasometry. A value of about 1.2 was found when the incubation medium was phosphate-buffered serum substitute with glucose as the sole substrate. This value suggests that endogenous lipids and amino acids do not contribute significantly to strial respiratory metabolism and that carbohydrate is the primary fuel in vitro. A high activity of the hexose monophosphate pathway may be responsible for raising the respiroatyr quotient above unity.

Animals↗