Pharmacological validation of a telemetric model for the measurement of bronchoconstriction in conscious rats.
BACKGROUND
Telemetric measurement of intra-pleural pressure in conscious animals that are restrained in head-out plethysmography chambers enables determination of airway resistance. Originally proposed over 10 years ago, pharmacological validation of this technique is limited. Here airway resistance in conscious, instrumented rats was compared to measurement in anaesthetised rats via a fluid filled oesophageal catheter following administration of two different pharmacological agents.


METHODS
Male rats were implanted with telemetry devices and were trained to accept the restraint of head-out plethysmography chambers. A separate group of male rats were anaesthetised, placed in a body-enclosed plethysmography chamber and were prepared with a tracheal, oesphageal and jugular vein cannulae. Methacholine or NECA were given intravenously and changes in ventilation and airway resistance were measured.


RESULTS
The pressure signal obtained in the telemetered rats was found to be extremely variable. Variability was confounded by excessive struggling, particularly during the infusion periods. Misplacement of the pressure sensitive catheter tip and prior habituation to the chamber were not factors in signal variability. Consequently, no dose-response relationship to either pharmacological agent was established in this model. Dose-dependent increases in resistance to both methacholine and NECA were measured in anaesthetised rats using body-enclosed plethysmography.


CONCLUSIONS
Given the variability of the pressure signal within and between rats, the feasibility of a model in conscious rats for the measurement of airway resistance is questioned. Improved restraint methods or alternative models in conscious animals should therefore be explored. In the meantime, assessment of airway resistance is best confined to the anaesthetised rat.
Ewart
Lorna C
LC
Safety Pharmacology, Global Safety Assessment, AstraZeneca R&D Alderley Park, Macclesfield, Cheshire, SK10 4TG, United Kingdom. lorna.ewart@astrazeneca.com
Haley
Michael
M
Bickerton
Sue
S
Bright
Jonathan
J
Elliott
Katherine
K
McCarthy
Alan
A
Williams
Lisa
L
Ricketts
Sally-Ann
SA
Holland
Tom
T
Valentin
Jean-Pierre
JP
D019830:Adenosine-5'-(N-ethylcarboxamide); D000403:Airway Resistance / Q000187:drug effects; D000758:Anesthesia; D000818:Animals; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D002404:Catheterization; D003243:Consciousness; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D010993:Plethysmography, Whole Body; D010994:Pleura / Q000502:physiology; D011312:Pressure; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013686:Telemetry / Q000379:methods*
D016085:Bronchoconstrictor Agents; D018721:Muscarinic Agonists; D058906:Purinergic P1 Receptor Agonists; D016210:Methacholine Chloride; D019830:Adenosine-5'-(N-ethylcarboxamide)