Respiratory mechanics: comparison of Beagle dogs, Göttingen minipigs and Cynomolgus monkeys.
BACKGROUND
When the no observed adverse effect level (NOAEL) is determined by respiratory safety pharmacology, follow-up studies are warranted and may include airway resistance and compliance. Respiratory mechanics in commonly used large animal species (Beagle dogs, Cynomolgus monkeys, and Göttingen minipigs) were compared.


METHODS
Eighteen animals were used (3/sex/species) in an anesthetized model (propofol infusion) with pancuronium as a neuromuscular blocker. Parameters of respiratory mechanics were evaluated at baseline and at peak drug effect. Resistance (Rrs) and elastance (Ers) were measured by applying a single frequency forced oscillation (0.5 Hz) to the subject's airway opening and fitting the flow, volume and pressure data to the single compartment model of the lung. Increasing doses of intravenous (IV) methacholine were administered in all three species, as well as doubling aerosolized concentrations of the same bronchoconstrictor agent before and after inhaled albuterol.


RESULTS
The slope of the IV methacholine dose-response curve for Rrs was similar in dogs and monkeys and both species differed from minipigs, which showed greater reactivity. At the highest IV dose tested, minipigs also reached higher levels of bronchoconstriction than the other two species. They were followed, in decreasing order, by dogs and monkeys. Albuterol induced a significant decrease in the slope of the dose-response curve only in dogs and monkeys.


CONCLUSIONS
Scientific literature is available on respiratory mechanics in monkeys and dogs but not in minipigs. Our results suggest that minipigs were more reactive than dogs and monkeys to IV methacholine while less sensitive to inhaled albuterol.
Animal Research Group in Pharmacology of Quebec (GREPAQ), Department of Veterinary Biomedical Sciences, Faculté de Médecine Vétérinaire, Université de Montréal, P.O. Box 5000, Saint-Hyacinthe, Quebec, J2S 7C6, Canada; Département de Psychiatrie et Neurosciences, Centre Hospitalier Universitaire Laval, Université Laval, 2705 Boulevard Laurier, Québec, Québec, G1V 4G2, Canada.
Geoffrey
G
Truchetti
Animal Research Group in Pharmacology of Quebec (GREPAQ), Department of Veterinary Biomedical Sciences, Faculté de Médecine Vétérinaire, Université de Montréal, P.O. Box 5000, Saint-Hyacinthe, Quebec, J2S 7C6, Canada.
Eric
E
Troncy
SCIREQ Scientific Respiratory Equipment Inc., 6600 St-Urbain, Suite 300 Montreal, Québec, H2S 3G8, Canada.
Annette
A
Robichaud
SCIREQ Scientific Respiratory Equipment Inc., 6600 St-Urbain, Suite 300 Montreal, Québec, H2S 3G8, Canada.
Leslie
L
Gold
SCIREQ Scientific Respiratory Equipment Inc., 6600 St-Urbain, Suite 300 Montreal, Québec, H2S 3G8, Canada.
Thomas
T
Schuessler
CiTox-LAB - North-America, Inc., 445 Armand Frappier, Laval, Quebec, H7V 4B3, Canada.
Said
S
Maghezzi
Animal Research Group in Pharmacology of Quebec (GREPAQ), Department of Veterinary Biomedical Sciences, Faculté de Médecine Vétérinaire, Université de Montréal, P.O. Box 5000, Saint-Hyacinthe, Quebec, J2S 7C6, Canada; CiTox-LAB - North-America, Inc., 445 Armand Frappier, Laval, Quebec, H7V 4B3, Canada.
Leanne
L
Bassett
Animal Research Group in Pharmacology of Quebec (GREPAQ), Department of Veterinary Biomedical Sciences, Faculté de Médecine Vétérinaire, Université de Montréal, P.O. Box 5000, Saint-Hyacinthe, Quebec, J2S 7C6, Canada; CiTox-LAB - North-America, Inc., 445 Armand Frappier, Laval, Quebec, H7V 4B3, Canada. Electronic address: authiers@ca.citoxlab.com.
Simon
S
Authier
D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D004285:Dogs / Q000502:physiology*; D005260:Female; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008252:Macaca fascicularis / Q000502:physiology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D013552:Swine / Q000502:physiology*; D013556:Swine, Miniature / Q000502:physiology*
D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D000420:Albuterol
Dog; Minipig; Monkey; Pulmonary elastance; Pulmonary resistance; Respiratory mechanics