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J Pharmacol Toxicol Methods. 2014 Jul-Aug;70(1):62-5. doi: 10.1016/j.vascn.2014.05.001. Epub 2014 May 21.

Non-invasive measure of respiratory mechanics and conventional respiratory parameters in conscious large animals by high frequency Airwave Oscillometry.

Author information

1
CIToxLAB North America, 445 Armand Frappier, Laval, QC, Canada, H7V 4B3.
2
Faculty of Veterinary Medicine, University of Montreal, P.O. Box 5000, St-Hyacinthe, QC, Canada, J2S 7C6.
3
SCIREQ Scientific Respiratory Equipment Inc., 6600 St-Urbain, Montreal, QC, Canada, H2S 3G8.
4
SCIREQ Scientific Respiratory Equipment Inc., 6600 St-Urbain, Montreal, QC, Canada, H2S 3G8; THORASYS Thoracic Medical Systems Inc., 6600 rue St-Urbain, Montreal, QC, Canada, H2S 3G8.
5
CIToxLAB North America, 445 Armand Frappier, Laval, QC, Canada, H7V 4B3; Faculty of Veterinary Medicine, University of Montreal, P.O. Box 5000, St-Hyacinthe, QC, Canada, J2S 7C6. Electronic address: authiers@ca.citoxlab.com.

Abstract

INTRODUCTION:

A number of drugs in clinical trials are discontinued due to potentially life-threatening airway obstruction. As some drugs may not cause changes in core battery parameters such as tidal volume (Vt), respiratory rate (RR) or minute ventilation (MV), including measurements of respiratory mechanics in safety pharmacology studies represents an opportunity for design refinement. The present study aimed to test a novel non-invasive methodology to concomitantly measure respiratory system resistance (Rrs) and conventional respiratory parameters (Vt, RR, MV) in conscious Beagle dogs and cynomolgus monkeys.

METHODS:

An Airwave Oscillometry system (tremoFlo; THORASYS Inc., Montreal, Canada) was used to concomitantly assess Rrs and conventional respiratory parameters before and after intravenous treatment with a bronchoactive agent. Respiratory mechanics measurements were performed by applying a short (i.e. 16s) single high frequency (19Hz) waveform at the subject's airway opening via a face mask. During measurements, pressure and flow signals were recorded. After collection of baseline measurements, methacholine was administered intravenously to Beagle dogs (n=6) and cynomolgus monkeys (n=4) at 8 and 68μg/kg, respectively.

RESULTS:

In dogs, methacholine induced significant increases in Vt, RR and MV while in monkeys, it only augmented RR. A significant increase in Rrs was observed after methacholine administration in both species with mean percentage peak increases from baseline of 88 (53)% for dogs and 28 (16)% for cynomolgus monkeys.

CONCLUSION:

Airwave Oscillometry appears to be a promising non-invasive methodology to enable respiratory mechanics measurements in conscious large animals, a valuable refinement in respiratory safety pharmacology.

KEYWORDS:

Airwave Oscillometry; Airway resistance; Dog; Methacholine; Monkey; Respiratory; Safety pharmacology

PMID:
24857836
DOI:
10.1016/j.vascn.2014.05.001
[Indexed for MEDLINE]

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