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Biomedical subjects

E Ferrary

Publications and source records attributed to E Ferrary.

25 records · Page 2Linked to original sources

[Effects of mannitol on the fluids of the internal ear. Use in the treatment of deafness].

The action of mannitol upon the inner ear fluids was studied experimentally by means of kinetics of mannitol entry into cochlear perilymph and endolymph in rats. A daily two hours infusion of 10% mannitol induces an osmotic water flow from cochlear fluids toward plasma. Following this therapeutic protocol, progressive, non-tumoral sensorineural hearing loss is enhanced in 32% of the cases. The rate of hearing improvement is larger than 50% in case of Ménière's disease. For sudden hearing loss, 75% of the cases are improved by mannitol, and 92% of the cases when the delay between the hearing loss onset and the mannitol therapy is less than two weeks. Sudden hearing loss should be considered as a sensory emergency.

Adult

Production of endolymph in the semicircular canal of the frog Rana esculenta.

The mechanisms of secretion of endolymph were studied in vitro in the isolated inner ear of the frog. Prior to in vitro experiments, the composition of perilymph was evaluated in vivo and compared to that of plasma. Composition of perilymph resembled that of an extracellular fluid, although Na and Cl concentrations were higher and K concentration was lower in perilymph than in plasma water. No difference in Ca and Mg concentrations was observed between these two fluids. Osmolality averaged 227 mosmol/kg H2O in perilymph and 183 mosmol/kg H2O in plasma. Endolymph in frog inner ear corresponded in chemical pattern to mammalian endolymph. K and Na concentrations in endolymph collected from the ampulla of the posterior vertical semicircular canal averaged 121.1 mM and 2.5 mM, respectively. Osmolality of endolymph was 237 mosmol/kg H2O. K and Na concentrations were unaltered when inner ears were incubated for 24 h either at 15 degrees C or at 4 degrees C. Addition of ouabain (10(-4) M) to the perilymph-like bathing solution altered greatly Na and K composition of endolymph after incubation for 3 h at 15 degrees C. The Na and K concentration gradients between endolymph and the bath were abolished after incubation for 24 h. Ligatures of the posterior vertical semicircular canal were performed at different sites to isolate some parts of the canal, i.e. the ampulla and the non-ampullar duct. K concentration in the ampulla after incubation for 24 h remained as high as 20 times that in the bath. This K gradient was abolished in the presence of ouabain (10(-4) M). High K concentration could be maintained in the non-ampullar part of the semicircular canal only if the latter communicated with the ampulla. It is concluded that endolymph is actively secreted into the ampulla of the semicircular canal. Na+-K+-activated ATPase in the ampullar dark cells may energize the ouabain sensitive ionic transports that are involved in the production of endolymph. Endolymph secreted into the ampulla would spread intraluminally to account for the high K and low Na concentrations of the fluid which fills the non-secretory part of the semicircular canal.

Animals

Prostaglandin synthesis by the cochlea of the guinea pig. Influence of aspirin, gentamicin, and acoustic stimulation.

This study describes the synthesis of prostaglandins (PGs) by the vascular structures of the inner ear (lateral wall = stria vascularis and spiral ligament) in vitro. The main PGs produced were PGI2, PGF2 alpha and PGE2. PGI2 and PGF2 alpha were also found in the perilymph. A 350 mg/kg ip injection of aspirin decreased PG synthesis by the lateral wall and PG levels in perilymph. This effect was reversed after 3 days. Gentamicin (10(-9) to 10(-5) M) decreased significantly and reversibly PG synthesis in vitro, as did 100 mg/kg ip injection. Acoustic stimulation increased ex vivo PGI2 and PGE2 synthesis without modifying PG levels in perilymph. Results suggest that PGs could be one humoral mediator of the cochlear microcirculation homeostasis, and, possibly, of the circulatory disturbances reported after acoustic stimulation. The decreased PG synthesis after gentamicin treatment could account for the angiotoxic component observed in aminoglycoside ototoxicity.

Acoustic Stimulation

Electrochemical heterogeneity of the cochlear endolymph: effect of acetazolamide.

The electrochemical composition of endolymph (EL) of two adjacent cochlear turns was studied in anesthetized rats. Differences in [K]EL, [Cl]EL, and endocochlear potential (EP) were found between the basal turn (165.6 +/- 3.0 mM, n = 14; 144.6 +/- 2.1 mM, n = 14;96.6 +/- 1.9 mV, n = 5, respectively) and the middle turn (155.7 +/- 2.5 mM, n = 15; 133.2 +/- 1.5 mM, n = 15; 87.0 +/- 1.6 mV, n = 6, respectively). The pH values of inner ear fluids were evaluated with 5,5-dimethyloxazolidine-2,4-dione: EL pH of either turn was not different from blood and perilymph (PL) pH. Acetazolamide (40 mg X kg body wt-1) reduced EP and [Cl]EL at each turn by about 20 and 6%, respectively, but [K]EL was unchanged. The electrochemical differences between the two turns persisted. Acetazolamide produced a 0.2-unit decrease in blood pH while the pH values of EL and PL remained unchanged. These results suggest the existence of an electrochemical gradient within EL from the base to the apex of the cochlea involving K+ and Cl- concentrations. H+ and HCO-3 do not appear to participate in this gradient, and the acid-base status in EL could be maintained both by active H+ transport into EL and by HCO-3 formation in the cochlear epithelium.

Acetazolamide

Inter- and intracompartmental osmotic gradients within the rat cochlea.

The osmolality and the electrochemical composition of the endolymph, a potassium-rich positively polarized extracellular fluid in the cochlea, was studied in the rat. Endolymph of each cochlear turn was hyperosmotic to perilymph and plasma. Osmolalities (mosmol/kg H2O) were 329 +/- 2.9 (mean +/- SE) (n = 13) in basal turn endolymph, 322 +/- 2.7 (n = 9) in middle turn endolymph, 317 +/- 5.2 (n = 3) in apical turn endolymph, 289 +/- 3.1 (n = 14) in perilymph of the scala vestibuli, and 298 +/- 1.8 (n = 7) in plasma. Moreover, differences in osmolality and electrochemical composition of endolymph, involving resting potential and K and Cl concentrations, were observed between the basal and the middle cochlear turns, suggesting the presence of an electrical and osmotic gradient within endolymph, declining from the base to the apex of the cochlea. The active potassium transport into endolymph, located presumably in the stria vascularis, could account for both the internal and external osmotic gradients.

Animals

Electrochemical composition of the cochlear fluids in the early experimental hydrops. Preliminary results.

The composition of endolymph and perilymph was studied in the guinea pig cochlea after 2 and 6 weeks of blockage of the vestibular aqueduct in an experimental model of hydrops. Compound action potential was monitored several times in the observation period. The endocochlear potential was measured and the endolymph was sampled at the first and third turns of the scala media. The Na, K, and Cl concentrations were determined in nanolitre aliquots of endolymph and of perilymph, the latter sampled from the basal scala vestibuli. After 2 weeks, no change in endolymphatic electrochemical composition was observed. After 6 weeks, endocochlear potential was decreased by 25% at both cochlear turns; K concentration was decreased in endolymph of the basal turn and Cl concentration was decreased in both turns; the calculated osmolality (Na + K + Cl) was decreased in both turns. These results indicate that the blockage of the vestibular aqueduct induced early auditory dysfunction whereas alterations of the electrochemical composition of endolymph occurred later after a time lag of more than 2 and less than 6 weeks.

Action Potentials

Strial prostaglandins and leukotrienes. Biochemical characteristics and interrelationship with furosemide.

Synthesis of prostaglandins (PGs) was characterized in the lateral wall (LW) of guinea-pig cochlea. Basal synthesis at 37 degrees C was about 480 pg/LW (12.8 ng X mg-1 protein) for PGI2 and 85 pg/LW (2.3 ng X mg-1 protein) for PGE2, levelling out after 10 min of incubation. Incubation with arachidonic acid (10(-5) M) increased PGI2 and PGE2 synthesis by 44% and 1020%, respectively, showing that arachidonic acid availability is a synthesis-limiting factor. The stimulating effect of the Ca++ ionophore A23187 (5 X 10(-6) M) on PG synthesis was weak (about +50%) but was enhanced (about +140%) by preincubation with arachidonic acid. Angiotensin II (10(-6) M), vasopressin (5 X 10(-7) M), and furosemide (10(-8) to 10(-3) M) did not alter PG secretion. Neither aspirin nor indomethacin prevented the development of furosemide ototoxicity (endocochlear potential) in the rat. Perfusion with PGI2 influenced the furosemide effect in some instances.

Angiotensin II