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Perilymph Kinetics of FITC-Dextran Reveals Homeostasis Dominated by the Cochlear Aqueduct and Cerebrospinal Fluid.
J Assoc Res Otolaryngol. 2015 Jun; 16(3):357-71.JA

Abstract

Understanding how drugs are distributed in perilymph following local applications is important as local drug therapies are increasingly used to treat disorders of the inner ear. The potential contribution of cerebrospinal fluid (CSF) entry to perilymph homeostasis has been controversial for over half a century, largely due to artifactual contamination of collected perilymph samples with CSF. Measures of perilymph flow and of drug distribution following round window niche applications have both suggested a slow, apically directed flow occurs along scala tympani (ST) in the normal, sealed cochlea. In the present study, we have used fluorescein isothiocyanate-dextran as a marker to study perilymph kinetics in guinea pigs. Dextran is lost from perilymph more slowly than other substances so far quantified. Dextran solutions were injected from pipettes sealed into the lateral semicircular canal (SCC), the cochlear apex, or the basal turn of ST. After varying delays, sequential perilymph samples were taken from the cochlear apex or lateral SCC, allowing dextran distribution along the perilymphatic spaces to be quantified. Variability was low and findings were consistent with the injection procedure driving volume flow towards the cochlear aqueduct, and with volume flow during perilymph sampling driven by CSF entry at the aqueduct. The decline of dextran with time in the period between injection and sampling was consistent with both a slow volume influx of CSF (~30 nL/min) entering the basal turn of ST at the cochlear aqueduct and a CSF-perilymph exchange driven by pressure-driven fluid oscillation across the cochlear aqueduct. Sample data also allowed contributions of other processes, such as communications with adjacent compartments, to be quantified. The study demonstrates that drug kinetics in the basal turn of ST is complex and is influenced by a considerable number of interacting processes.

Authors+Show Affiliations

Department of Otolaryngology, Washington University School of Medicine, Box 8115, 660, South Euclid Avenue, St. Louis, MO, 63110, USA, salta@ent.wustl.edu.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25801074

Citation

Salt, A N., et al. "Perilymph Kinetics of FITC-Dextran Reveals Homeostasis Dominated By the Cochlear Aqueduct and Cerebrospinal Fluid." Journal of the Association for Research in Otolaryngology : JARO, vol. 16, no. 3, 2015, pp. 357-71.
Salt AN, Gill RM, Hartsock JJ. Perilymph Kinetics of FITC-Dextran Reveals Homeostasis Dominated by the Cochlear Aqueduct and Cerebrospinal Fluid. J Assoc Res Otolaryngol. 2015;16(3):357-71.
Salt, A. N., Gill, R. M., & Hartsock, J. J. (2015). Perilymph Kinetics of FITC-Dextran Reveals Homeostasis Dominated by the Cochlear Aqueduct and Cerebrospinal Fluid. Journal of the Association for Research in Otolaryngology : JARO, 16(3), 357-71. https://doi.org/10.1007/s10162-015-0512-1
Salt AN, Gill RM, Hartsock JJ. Perilymph Kinetics of FITC-Dextran Reveals Homeostasis Dominated By the Cochlear Aqueduct and Cerebrospinal Fluid. J Assoc Res Otolaryngol. 2015;16(3):357-71. PubMed PMID: 25801074.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Perilymph Kinetics of FITC-Dextran Reveals Homeostasis Dominated by the Cochlear Aqueduct and Cerebrospinal Fluid. AU - Salt,A N, AU - Gill,R M, AU - Hartsock,J J, Y1 - 2015/03/24/ PY - 2014/12/02/received PY - 2015/02/13/accepted PY - 2015/3/25/entrez PY - 2015/3/25/pubmed PY - 2016/2/9/medline SP - 357 EP - 71 JF - Journal of the Association for Research in Otolaryngology : JARO JO - J Assoc Res Otolaryngol VL - 16 IS - 3 N2 - Understanding how drugs are distributed in perilymph following local applications is important as local drug therapies are increasingly used to treat disorders of the inner ear. The potential contribution of cerebrospinal fluid (CSF) entry to perilymph homeostasis has been controversial for over half a century, largely due to artifactual contamination of collected perilymph samples with CSF. Measures of perilymph flow and of drug distribution following round window niche applications have both suggested a slow, apically directed flow occurs along scala tympani (ST) in the normal, sealed cochlea. In the present study, we have used fluorescein isothiocyanate-dextran as a marker to study perilymph kinetics in guinea pigs. Dextran is lost from perilymph more slowly than other substances so far quantified. Dextran solutions were injected from pipettes sealed into the lateral semicircular canal (SCC), the cochlear apex, or the basal turn of ST. After varying delays, sequential perilymph samples were taken from the cochlear apex or lateral SCC, allowing dextran distribution along the perilymphatic spaces to be quantified. Variability was low and findings were consistent with the injection procedure driving volume flow towards the cochlear aqueduct, and with volume flow during perilymph sampling driven by CSF entry at the aqueduct. The decline of dextran with time in the period between injection and sampling was consistent with both a slow volume influx of CSF (~30 nL/min) entering the basal turn of ST at the cochlear aqueduct and a CSF-perilymph exchange driven by pressure-driven fluid oscillation across the cochlear aqueduct. Sample data also allowed contributions of other processes, such as communications with adjacent compartments, to be quantified. The study demonstrates that drug kinetics in the basal turn of ST is complex and is influenced by a considerable number of interacting processes. SN - 1438-7573 UR - https://www.unboundmedicine.com/medline/citation/25801074/Perilymph_Kinetics_of_FITC_Dextran_Reveals_Homeostasis_Dominated_by_the_Cochlear_Aqueduct_and_Cerebrospinal_Fluid_ DB - PRIME DP - Unbound Medicine ER -