Repeated assessment of cardiovascular and respiratory functions using combined telemetry and whole-body plethysmography in the rat.
BACKGROUND
As the currently recommended laboratory techniques for assessing cardiovascular and respiratory functions are telemetry and plethysmography, we therefore combined both in a single rodent model. The purpose of the present work was to assess the potential influence of body growth on the recorded parameters, to verify the sensitivity of the system to detect well known pharmacological effects of reference drugs, and to determine their reproducibility over time.


METHODS
Telemetry instrumented rats were enrolled in successive experiments over a total of 5 months. In each run, they were placed in individual plethysmography chambers for 6h, and received a single intraperitoneal injection of vehicle or test compound. Heart rate, blood pressure, body temperature and respiratory parameters were measured in real time. Six of these 16 rats were submitted 5 times at one month intervals to a vehicle injection, and six rats received theophylline (30 mg/kg) twice at 4 months interval. Nine other reference compounds were also tested at a single dose.


RESULTS
Analysis of baseline data mainly showed correlations between body weight or age and heart rate, as well as tidal volume. In the five successive runs, handling-induced perturbations were noted in all the parameters during 60 to 90 min. The effects of the different reference drugs were consistent with data published in animals and man. The response to theophylline was qualitatively similar at 4 months interval.


CONCLUSIONS
We established a combined model of telemetry and plethysmography in the conscious rat, allowing the reuse of the animals over several successive pharmacodynamic studies. Although a shift of some parameters, particularly heart rate and tidal volume, was noted with age and body weight, this can easily be managed by appropriate design measures. We showed that the combined system can detect negative or positive effects on both cardiovascular and respiratory functions with enough sensitivity.
Delaunois
Annie
A
Department of Non Clinical Development, Non Clinical Safety Pharmacology Group, UCB Pharma SA, B-1420 Braine-l'Alleud, Belgium.
Dedoncker
Paul
P
Hanon
Etienne
E
Guyaux
Michel
M
D000420:Albuterol / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology; D003061:Codeine / Q000008:administration & dosage / Q000494:pharmacology; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology; D010424:Pentobarbital / Q000008:administration & dosage / Q000494:pharmacology; D010993:Plethysmography, Whole Body; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D012119:Respiration / Q000187:drug effects; D012143:Respiratory Physiological Phenomena / Q000187:drug effects*; D012680:Sensitivity and Specificity; D013686:Telemetry / Q000379:methods*; D013806:Theophylline / Q000008:administration & dosage / Q000494:pharmacology*; D013990:Tidal Volume / Q000187:drug effects; D013997:Time Factors
D001569:Benzodiazepines; D009538:Nicotine; D001285:Atropine; D002217:Carbachol; D013806:Theophylline; D010424:Pentobarbital; D009543:Nifedipine; D003000:Clonidine; D003975:Diazepam; D000420:Albuterol; D003061:Codeine