Journal article
Respiratory function in rats restrained for extended periods: Assessment of the effects of bethanecol
Journal of Pharmacological and Toxicological Methods, Vol.52(1), pp.83-89
2005
PMID: 15914033
Abstract
Introduction:
The ICH guideline S7A recommends that the effects of drugs on the respiratory system are evaluated in laboratory mammals prior to administration in man. Previously, animals have been placed in plethysmography chambers for short durations. This study investigates the possibility of restraining animals in chambers for a longer duration to assess respiratory function over extended periods.
Methods:
Respiratory function in conscious rats was assessed using plethysmography chambers where the rat body was enclosed in a sealed chamber while the head was free. Thoracic movements were measured by pressure transducers linked to a Buxco amplifier system and respiratory parameters were captured and analyzed by the Notocord HEM data acquisition system. Each animal was subjected to 5 acclimatization sessions of escalating duration (1, 2, 4, 5, and 6 hours (h)) over 5 days prior to testing, with a baseline recording session conducted the day prior to dosing. Animals (8 males/group) were dosed subcutaneously with saline or bethanecol (3, 10, or 30 mg/kg) and placed in the chambers for 6 h of continuous recording. Additionally, a recording session was conducted at 24 h post-dose.
Results:
Subcutaneous administration of 30 mg/kg bethanecol decreased respiration rate by up to 33% during the first 1.5 h post-dose and increased tidal volume by up to 46% from 0.25 to 1.25 h post-dose when compared to vehicle group data. A decrease in minute volume of up to 33% was observed 0.25 h following administration of the 10 and 30 mg/kg doses.
Discussion:
These data show a respiratory depression caused by the cholinergic agonist bethanecol, an effect partially compensated for by an increase in tidal volume. This also demonstrates the ability to continuously restrain and record respiratory parameters in conscious rats for up to 6 h without any negative impact on the quality of the data.
Details
- Title
- Respiratory function in rats restrained for extended periods: Assessment of the effects of bethanecol
- Authors
- David Harris (Author) - Heriot-Watt UniversityMags Graham (Author) - Heriot-Watt UniversityJoanne Price (Author) - Heriot-Watt UniversityFiona Munro (Author) - Heriot-Watt UniversityAlison Templeton (Author) - Heriot-Watt UniversityRoss Young (Author) - Heriot-Watt UniversityKirsty Paterson (Author) - Heriot-Watt UniversityLynne Anderson (Author) - Heriot-Watt UniversitySusanne Gillies (Author) - Heriot-Watt UniversitySue McKendrick (Author) - Heriot-Watt UniversityGill Low (Author) - Heriot-Watt UniversityLeslie Patmore (Author) - Heriot-Watt UniversityRebeccah Bodine (Author) - Lilly Research Laboratories, Greenfield, Indiana, USAMary Jeanne Kallman (Author) - Lilly Research Laboratories, Greenfield, Indiana, USAWherly P Hoffman (Author) - Lilly Research Laboratories, Greenfield, Indiana, USACindy Lee (Author) - Lilly Research Laboratories, Greenfield, Indiana, USARonald K Wolff (Author) - Lilly Research Laboratories, Greenfield, Indiana, USA
- Publication details
- Journal of Pharmacological and Toxicological Methods, Vol.52(1), pp.83-89
- Publisher
- Elsevier Inc.
- DOI
- 10.1016/j.vascn.2005.03.007
- ISSN
- 1873-488X
- PMID
- 15914033
- Organisation Unit
- Office of the Deputy Vice-Chancellor (Research and Innovation); University of the Sunshine Coast, Queensland
- Language
- English
- Record Identifier
- 99550991502621
- Output Type
- Journal article
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