Mannitol and the blood-labyrinth barrier
Abstract Background Characterization of the blood labyrinth barrier (BLB) is extremely important to determine whether the BLB can be manipulated pharmacologically. However, experiments to investigate the BLB are technically difficult to perform. In this report, we demonstrated a unique method of con...
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SAGE Publishing
2017-12-01
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| Series: | Journal of Otolaryngology - Head and Neck Surgery |
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| Online Access: | http://link.springer.com/article/10.1186/s40463-017-0245-8 |
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| author | Trung N. Le Brian W. Blakley |
| author_facet | Trung N. Le Brian W. Blakley |
| author_sort | Trung N. Le |
| collection | DOAJ |
| description | Abstract Background Characterization of the blood labyrinth barrier (BLB) is extremely important to determine whether the BLB can be manipulated pharmacologically. However, experiments to investigate the BLB are technically difficult to perform. In this report, we demonstrated a unique method of controlling the BLB, and established the pharmacokinetics of gentamicin in perilymph, cerebrospinal fluid (CSF) and blood with and without mannitol. Study design Controlled animal research project. Methods Permeability of the BLB and the blood brain barrier (BBB) to gentamicin with and without mannitol was studied by collecting 175 samples from 44 guinea pigs using concentrations relevant to human clinical situations. Samples were taken from two groups of 22 animals, with each animal undergoing sampling at a different time after administration of either 10 mg/ml gentamicin (4 mg/kg) (Gardena, CA) alone or gentamicin with 20% mannitol (250 mg/kg) (Mallinckrodt Inc., KY). The sample times varied from 0.5 to 17.5 h post-infusion. Samples were also taken from 4 animals as negative controls after administration of normal saline. Our goal was to simultaneously assess the pharmacokinetics of gentamicin in each of three different fluid samples in the same animal. Thus at the pre-determined post-infusion sampling time, each animal was sampled once for perilymph, CSF, and blood before being euthanized. Each animal contributed to a single time point on the subsequent pharmacokinetic curves with more than one animal per time point. Results Mannitol increased the rate of entry and egress of gentamicin through BLB significantly (p = 0.0044) but the effects on the BBB did not reach statistical significance (p = 0.581). Mannitol did not alter renal clearance of gentamicin from the blood (p = 0.433). The concentration of gentamicin in perilymph and CSF was always significantly lower than in blood. Conclusions Mannitol administration transiently increases the permeability of the BLB. Potential clinical benefits may accrue from selected timing of administration of osmotic agents such as mannitol augmenting the rate of entry and egress of compounds such as gentamicin into and out of perilymph. |
| format | Article |
| id | doaj-art-fd231186ea304ffd981ff1366f47c7f1 |
| institution | Kabale University |
| issn | 1916-0216 |
| language | English |
| publishDate | 2017-12-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Journal of Otolaryngology - Head and Neck Surgery |
| spelling | doaj-art-fd231186ea304ffd981ff1366f47c7f12025-02-03T00:22:57ZengSAGE PublishingJournal of Otolaryngology - Head and Neck Surgery1916-02162017-12-014611710.1186/s40463-017-0245-8Mannitol and the blood-labyrinth barrierTrung N. Le0Brian W. Blakley1Department of Otolaryngology – Head & Neck Surgery, Sunnybrook Research Institute, University of TorontoDepartment of Otolaryngology – Head & Neck Surgery, University of ManitobaAbstract Background Characterization of the blood labyrinth barrier (BLB) is extremely important to determine whether the BLB can be manipulated pharmacologically. However, experiments to investigate the BLB are technically difficult to perform. In this report, we demonstrated a unique method of controlling the BLB, and established the pharmacokinetics of gentamicin in perilymph, cerebrospinal fluid (CSF) and blood with and without mannitol. Study design Controlled animal research project. Methods Permeability of the BLB and the blood brain barrier (BBB) to gentamicin with and without mannitol was studied by collecting 175 samples from 44 guinea pigs using concentrations relevant to human clinical situations. Samples were taken from two groups of 22 animals, with each animal undergoing sampling at a different time after administration of either 10 mg/ml gentamicin (4 mg/kg) (Gardena, CA) alone or gentamicin with 20% mannitol (250 mg/kg) (Mallinckrodt Inc., KY). The sample times varied from 0.5 to 17.5 h post-infusion. Samples were also taken from 4 animals as negative controls after administration of normal saline. Our goal was to simultaneously assess the pharmacokinetics of gentamicin in each of three different fluid samples in the same animal. Thus at the pre-determined post-infusion sampling time, each animal was sampled once for perilymph, CSF, and blood before being euthanized. Each animal contributed to a single time point on the subsequent pharmacokinetic curves with more than one animal per time point. Results Mannitol increased the rate of entry and egress of gentamicin through BLB significantly (p = 0.0044) but the effects on the BBB did not reach statistical significance (p = 0.581). Mannitol did not alter renal clearance of gentamicin from the blood (p = 0.433). The concentration of gentamicin in perilymph and CSF was always significantly lower than in blood. Conclusions Mannitol administration transiently increases the permeability of the BLB. Potential clinical benefits may accrue from selected timing of administration of osmotic agents such as mannitol augmenting the rate of entry and egress of compounds such as gentamicin into and out of perilymph.http://link.springer.com/article/10.1186/s40463-017-0245-8Blood labyrinth barrierBlood brain barrierCerebrospinal fluidPerilymphGentamicinMannitol |
| spellingShingle | Trung N. Le Brian W. Blakley Mannitol and the blood-labyrinth barrier Journal of Otolaryngology - Head and Neck Surgery Blood labyrinth barrier Blood brain barrier Cerebrospinal fluid Perilymph Gentamicin Mannitol |
| title | Mannitol and the blood-labyrinth barrier |
| title_full | Mannitol and the blood-labyrinth barrier |
| title_fullStr | Mannitol and the blood-labyrinth barrier |
| title_full_unstemmed | Mannitol and the blood-labyrinth barrier |
| title_short | Mannitol and the blood-labyrinth barrier |
| title_sort | mannitol and the blood labyrinth barrier |
| topic | Blood labyrinth barrier Blood brain barrier Cerebrospinal fluid Perilymph Gentamicin Mannitol |
| url | http://link.springer.com/article/10.1186/s40463-017-0245-8 |
| work_keys_str_mv | AT trungnle mannitolandthebloodlabyrinthbarrier AT brianwblakley mannitolandthebloodlabyrinthbarrier |