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Biomedical subjects

A N Salt

Publications and source records attributed to A N Salt.

At least 19 recordsLinked to original sources
PubMed1992

Tetramethylammonium for in vivo marking of the cross-sectional area of the scala media in the guinea pig cochlea.

A physiologic technique was developed to measure endolymphatic cross-sectional area in vivo using tetramethylammonium (TMA) as a volume marker. The technique was evaluated in guinea pigs as an animal model. In the method, the cochlea was exposed surgically and TMA was injected into endolymph of the second turn at a constant rate by iontophoresis. The concentration of TMA was monitored during and after the injection using ion-selective electrodes. Cross-section estimates derived from the TMA concentration measurements were compared in normal animals and animals in which endolymphatic hydrops had been induced by ablation of the endolymphatic duct and sac 8 weeks earlier. The method demonstrated a mean increase in cross-sectional area of 258% in the hydropic group. Individually measured area values were compared with action potential threshold shifts and the magnitude of the endocochlear potential (EP). Hydropic animals typically showed an increase in threshold to 2 kHz stimuli and a decrease in EP. However, the degree of threshold shift or EP decrease did not correlate well with the degree of hydrops present.

Animals↗
PubMed1992

Permeability changes of the blood-labyrinth barrier measured in vivo during experimental treatments.

The communication between blood and cochlear perilymph was investigated using the tracer ion trimethylphenylammonium (TMPA). TMPA can be detected in micromolar concentrations by ion-selective microelectrodes, allowing it to be used as an almost ideal marker to study intercommunication between fluid compartments. TMPA-sensitive electrodes were sealed into the cochlear scalae, using procedures which avoided the artifactual displacement of perilymph by cerebrospinal fluid (CSF). TMPA was infused intravenously at a low rate to produce a plasma concentration of approximately 0.5, mM. The time course of entry into perilymph of scala tympani (ST), scala vestibuli (SV) and into CSF were compared. After 90 min infusion, the mean CSF concentration reached 14.3% of that measured in plasma. The TMPA concentrations measured in ST and SV perilymph were significantly lower than those recorded in CSF, only reaching an average of 6.5% and 3.7% of the plasma concentration respectively after 90 min. The slow entry of TMPA confirms the existence of a tight blood-labyrinth barrier, equivalent to the blood-brain or blood-CSF barriers. The rate of TMPA entry into perilymph was increased by epinephrine-induced hypertension or by simultaneous administration of histamine and prostaglandin E2. These treatments are presumed to increase the permeability of the blood-labyrinth barrier. Characterization and manipulation of blood-labyrinth barrier permeability could be important to our understanding cochlear pathology.

Animals↗
PubMed1992

[Solute movement across the round window membrane in comparison with that across the blood-labyrinth barrier].

The permeability of the normal round window membrane of the guinea pig to trimethylphenylammonium (TMPA) was assessed using ion-selective electrodes and compared with the rate of TMPA entry from the systemic blood circulation into the scala tympani (ST) of the cochlea across the so-called blood-labyrinth barrier. While the round window niche was irrigated with artificial perilymph containing 1 mM TMPA, the TMPA concentration in ST of the basal turn rose rapidly so as to reach 20-50% of the irrigating medium concentration in one hour. Following this procedure, the concentration declined significantly faster when the niche was subsequently irrigated with TMPA-free artificial perilymph than when the niche was left free of any fluid. This result shows that the membrane is fairly permeable to TMPA in both directions. Furthermore, TMPA entry from blood to STs of the basal and third turns was observed while the plasma TMPA concentration was maintained at about 0.5 mM by continuous intravenous infusion of isotonic 50 mM TMPA medium (1 part 150 mM TMPA + 2 parts lactated Ringer solution). TMPA appeared to distribute evenly from the blood to both turns at a much slower rate than across the round window membrane. In another experiment, the round window niche was irrigated with TMPA-free artificial perilymph during the intravenous infusion of 50 mM TMPA medium. The TMPA concentration increase in ST of the basal turn was greatly suppressed, whereas that of the third turn was not affected for at least an hour.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Calibration of ion-selective microelectrodes for use with high levels of interfering ions.

Ion-selective electrodes are often used in solutions which contain interfering ions. Calibration under these conditions is usually achieved by the fixed interference method, in which the concentration of the test ion is varied in a fixed background of interfering ion. The present paper describes a method for analyzing fixed interference calibration data which allows the Nicolski coefficients to be extracted using commercially available computer software. The method produces an accurate numeric description of the calibration curve. It also enables an accurate correction for the situation where the experimental level of interfering ion is not identical to that of the standard solutions.

Calibration↗
PubMed1991

Radial communication between the perilymphatic scalae of the cochlea. I: Estimation by tracer perfusion.

The degree to which radial exchange between scala tympani (ST) and scala vestibuli (SV) can occur has not previously been quantified. We have measured the amount of cross-communication in the third turn of the guinea pig cochlea using an ionic tracer, trimethylphenylammonium (TMPA). TMPA was perfused through one scala while TMPA concentrations were measured simultaneously in the perfused and non-perfused scalae. On the basis of the time course of TMPA increase recorded in the non-perfused scala, we were able to calculate rate constants for cross-leak and clearance. Cross-leak in the third turn occurred remarkably rapidly with a rate constant from ST to SV of 0.049 min-1 and from SV to ST of 0.031 min-1. These correspond to transfer half times of 14.2 and 22.4 min respectively. This result demonstrates that ST and SV in the third turn cannot be regarded as independent compartments.

Animals↗
PubMed1991

Radial communication between the perilymphatic scalae of the cochlea. II: Estimation by bolus injection of tracer into the sealed cochlea.

Radial communication between ST and SV was measured in the sealed cochlea by monitoring the dispersal of an ionic tracer, trimethylphenylammonium (TMPA) injected in the form of a minute bolus. Tracer movements were recorded by a pair of ion-selective electrodes sealed into the injected and non-injected scalae close to the injection site. Measurements were made in the basal or third turn of the guinea pig cochlea. In the third turn, radial communication occurred rapidly with a ST half time from ST to SV of 25 min and from SV to ST of 26 min. In the basal turn the communication was markedly slower, with a ST half time from ST to SV of 170 min and from SV to ST of 240 min. However, the difference between the basal and third turns can be shown to arise almost totally from differences in cross-sectional area of the perilymphatic scalae. When normalized with respect to scala cross-section, the process of tracer movement across the spiral ligament is similar in the basal and third turns. These results demonstrate that radial communication between scala tympani and scala vestibuli is an important route which must be considered in studies involving perilymph.

Animals↗
PubMed1991

Evaluation of procedures to reduce fluid flow in the fistulized guinea-pig cochlea.

The rate of longitudinal flow of fluid in scala tympani (ST) has been quantified under a number of experimental conditions. The method used to measure flow involved using a tracer ion (trimethylphenylammonium: TMPA) as a volume flow marker. Movement of marked perilymph was monitored by ion-selective microelectrodes which were capable of detecting exceedingly low concentrations of TMPA. Our results show that when the cochlea is perforated at the apex, flow rates of 400-500 nl/min are induced in ST, compared to the normal very slow rate of 2 nl/min when the cochlea is sealed. This artifactual flow of CSF through the perforated cochlea can be reduced to 6.9 nl/min by releasing the hydrostatic pressure of cerebrospinal fluid (CSF) or further reduced to 1.8 nl/min by surgically obstructing the cochlear aqueduct. In addition, we observed no basally-directed flow in ST when the round window (RW) was perforated, demonstrating that perilymph is not produced in volume as previously assumed. This study demonstrates the importance of separating artifactual flows, induced by the experimental procedures required to access the cochlear fluids, from the low flow rates which occur in normal, physiologic conditions.

Action Potentials↗
PubMed1990

Cochlear action potential tuning curves recorded with a derived response technique.

Previous action potential (AP) tuning curve methods have used a reduction in amplitude of the probe-elicited AP as an indication of tone-induced masking. The reduction criterion used in different studies has varied from 25% to 100%. For low level probe stimuli, which elicit a low-amplitude AP, this is a sensitive indicator. In contrast, for high-amplitude AP responses elicited by high-level stimuli, the required reduction in absolute terms is large, making it an insensitive indicator. AP tuning curves have been recorded using a sensitive method for detecting masker/probe interaction with a fixed criterion, unrelated to the unmasked AP amplitude. For each masking condition, a derived response was obtained by digitally subtracting the tone-masked AP waveform from the unmasked response. Derived responses are generated if there are ANY changes in the AP waveform induced by the masker, including amplitude changes, latency changes, or even changes in AP morphology not necessarily associated with the major peaks. A fixed criterion (10 microV) of tone-derived (TD) response was used as an indication of interaction of the responses to the masker and probe. Tuning curves generated by this method were compared with those generated by conventional amplitude reduction (AR) methods. TD tuning curves show different characteristics, especially with respect to increasing probe levels. They appear to give a good representation of the array of afferent fibers responding to a probe stimulus. In addition, frequency regions making minor contributions to the AP are better represented in TD tuning curves.

Animals↗
PubMed1990

Cochlear threshold assessment using tone-derived action potentials.

An evoked-potential technique has been evaluated which detects whether the cochlea responds to a continuous, low level tone. The technique involves recording the cochlear action potential (AP) response to a suprathreshold probe tone, first in the absence and then in the presence of a continuous masking tone at the same frequency. Subtraction of the masked AP waveform from the unmasked AP yields a 'derived' potential, provided the continuous tone is above the threshold of cochlear sensitivity. Derived AP responses may be recorded with continuous masking tones over 10 dB below the threshold to the probe stimulus. In normally hearing guinea pigs, the mean best derived threshold using a 10-microV response criterion was 7.1 dB SPL, compared to 18.9 dB for conventional AP thresholds. The tone-derived response appears to provide a more sensitive and frequency-specific method for determining cochlear thresholds.

Animals↗
PubMed1989

Perilymph composition in scala tympani of the cochlea: influence of cerebrospinal fluid.

A commonly used technique to obtain cochlear perilymph for analysis has been the aspiration of samples through the round window membrane. The present study has investigated the influence of the volume withdrawn on sample composition in the guinea pig. Samples of less than 200 nl in volume taken through the round window showed relatively high glycine content, comparable to the level found in samples taken from scala vestibuli. If larger volumes are withdrawn, lower glycine levels are observed. This is consistent with cerebrospinal fluid (having a low glycine content) being drawn into scala tympani through the cochlear aqueduct and contaminating the sample. The existence of a concentration difference for glycine between scala tympani perilymph and cerebrospinal fluid suggests the physiologic communication across the cochlear aqueduct is relatively small in this species. The observation of considerable exchange between cerebrospinal fluid and perilymph, as reported in some studies, is more likely to be an artifact of the experimental procedures, rather than of physiologic significance. Alternative sampling procedures have been evaluated which allow larger volumes of uncontaminated scala tympani perilymph to be collected.

Animals↗
PubMed1988

Volume flow rate of perilymph in the guinea-pig cochlea.

The rate of longitudinal flow of perilymph has been measured using an ionic tracer technique. Spread of the tracer trimethylphenylammonium (TMPA) along the perilymphatic scalae was monitored with ion-selective microelectrodes following injection of a minute bolus (approximately 50 nl) of 150 mM TMPAC1 one turn away. This amount of TMPA had virtually no toxic effect on cochlear function. The spread of tracer by longitudinal volume flow and passive diffusion were separated by comparing tracer movements in both apical and basal directions along the scalae in two groups of animals. Experimental findings were compared with a mathematical model which combined diffusion and volume flow. Our results demonstrated that when electrodes were completely sealed into the cochlea, the rate of longitudinal volume flow in scala tympani was extremely slow, approximately 1.6 nl/min in the apical direction. Longitudinal flow was not detectable in scala vestibuli. When the otic capsule was perforated, flow rates of over 1 microliter/min were recorded in scala tympani, probably as a result of cerebrospinal fluid entry through the cochlear aqueduct. When the cochlea was sealed (with recording electrodes in place) and cerebrospinal fluid pressure was released, there was no significant basally-directed flow of perilymph in scala tympani. These findings support the concept that perilymph composition is maintained by local, cochlear mechanisms which do not involve longitudinal volume flow. They provide strong evidence that perilymph is not secreted in one region and resorbed at a spatially distant site.

Action Potentials↗
PubMed1987

Mechanisms of endocochlear potential generation by stria vascularis.

It is commonly accepted that the endocochlear potential (EP) of the cochlea is generated by an electrogenic transport of potassium into scala media by the marginal cells of stria vascularis. We have studied the potential and potassium concentration gradients as stria vascularis was penetrated with double-barreled potassium selective electrodes in the guinea pig cochlea. Our data demonstrate that a region exists in stria which is positively polarized (higher than the EP), but which has a low (perilymph-like) potassium composition. It is concluded that EP cannot be generated by the marginal cells alone but may involve passive potassium movement across the apical membranes of the basal cells. A model is presented which is consistent with many anatomical and physiological features of stria vascularis.

Animals↗
PubMed1986

Direct measurement of longitudinal endolymph flow rate in the guinea pig cochlea.

The rate of longitudinal endolymph flow in the guinea pig cochlea has been measured with a novel tracer technique. The tracer we utilized was the tetramethylammonium (TMA) ion, the movement of which was monitored by ion-sensitive microelectrodes. Extremely small amounts of tracer were required as the electrodes could readily detect TMA concentrations in endolymph as low as 10 microM. TMA was introduced into scala media in the form of a small bolus, varying from 2-20 nl in volume. To examine whether longitudinal flow affects the dispersion of TMA in endolymph, we compared the characteristics of TMA spread to turn I following injection into turn II, with those of TMA spread to turn II following injection into turn I. The comparison of these data with an analytical model combining the processes of diffusion and volume flow demonstrates that the spread of tracer is dominated by passive diffusion processes with very little contribution from longitudinal endolymph flow. The rate of longitudinal endolymph flow between turn I and turn II was estimated to be less than 0.01 mm/min directed towards the basal turn. This value is considerably lower than recently published estimates using other techniques.

Cochlea↗
PubMed1979

The effect of raising the scala tympani potassium concentration on the tone-induced cochlear responses of the guinea pig.

Scala tympani (ST) in guinea pig was perfused with modified Ringer's solutions containing 5--50 mM potassium; tone-induced cochlear responses from the basal turn of ST were compared before, during and after perfusions. The compound nerve action potential (N1) and afterpotential (a/p) amplitudes were reduced, especially above 20 mM; the summating potential (SP) was variable, but its onset shape changed consistently with 13--20 mM levels. However, the cochlear microphonic amplitude (CM) remained substantially unchanged even at the 35 mM level. K+ concentration was monitored in ST with ion-sensitive pipettes. Stable levels were reached within 2 min, but N1 responses continued to fall beyond this time. Recovery to normal K+ levels took place spontaneously and the concentration curve which resulted showed a 2-slope characteristic. These experiments question whether elevated potassium concentration in scala tympani depolarizes the hair cells, and if it does, whether the hear cell resting potential is involved in the generation of the CM.

Acoustic Stimulation↗
PubMed1979

Effects of exposure to noise on ion movement in guinea pig cochlea.

Healthy guinea pigs were exposed to broad band noise at levels between 95 and 115 dBA for 7 days. A significant decrease of the sound-induced cochlear responses, together with a substantial increase of the endocochlear potential, was observed in guinea pigs exposed to noise at 105 or 115 dBA. Microsamples of the endolymph obtained from these guinea pigs showed a significant increase of K+ and Cl- concentrations and a decrease of Na+ concentration, when compared with those from control animals. The K+, Na+ and Cl- concentrations in the perilymph were not markedly affected by noise exposure. When the perilymphatic space was perfused with artificial perilymph containing 43K, 22Na or 36 Cl, the uptake of radiotracers into the endolymph showed a single exponential function of the perfusion time. When compared with rate constants in normal animals, the value of rate constant for K+ was significantly decreased in animals exposed to noise. These results indicate that ionic permeability changes of the endolymph-perilymph barrier are a significant factor in the physiological mechanisms underlying noise-induced hearing loss.

Animals↗
PubMed1979

Effects of noise on cochlear potentials and endolymph potassium concentration recorded with potassium-selective electrodes.

Guinea pig cochleas were exposed to either broad-band noise at intensities between 95 and 115 dBA or octave-band noise centered at 380 Hz or 4.2 kHz at intensities between 115 and 125 dB SPL. Cochlear microphonics (CM), summating potentials (SP) and action potentials (AP) were recorded from differential electrodes in the perilymphatic scalae between successive 20-min periods of noise exposure. The endocochlear potential (EP) and endolymph potassium concentration [Kendo+] were recorded continuously from scala media using double-barreled potassium-sensitive electrodes. It was found that the initial exposure to noise at 115 dBA produced considerable suppression of the CM and AP, while the EP and [Kendo+] were elevated above their normal values. When animals previously treated with kanamycin were subjected to the same level of noise exposure no systematic increase in either EP ro [Kendo+] was observed. After prolonged exposure to 380 Hz octave-band noise at 125 dB SPL, a slow decline of EP and [Kendo+] was observed. The relationships between the changes in EP, [Kendo+] and CM are discussed.

Animals↗