Respiratory inductive plethysmography as a method for measuring ventilatory parameters in conscious, non-restrained dogs.
BACKGROUND
Assessing the effects of new chemical entities on respiratory function in animal models is an essential component of preclinical drug safety evaluation. Methods currently available for measuring ventilatory parameters in conscious dogs generally utilize a plethysmograph chamber or a face mask equipped with a pneumotachograph attached to the snout of the animal. These methods require restraint and allow for only short, periodic measurements. Because of these limitations, respiratory inductive plethysmography (RIP) was evaluated as a possible new methodology that will allow for continuous monitoring of respiratory parameters in non-restrained dogs for extended periods of time.


METHODS
Straps containing inductive coils were placed around the thorax and abdomen to measure thoracic and abdominal excursions. The straps were contained within a protective jacket that was placed on the dogs and the electrical signals from the inductive coils were transmitted by telemetry to a receiver. The data were acquired and analyzed using the Vivometrics(R) LifeShirt(R) PreClinical System. Because postural changes can alter tidal volume measurements using RIP, the jacket also contained an accelerometer that was used to record postural changes during ventilatory measurements.


RESULTS
Measurement of ventilatory parameters in dogs following manual placement in different positions (e.g., standing, sitting, lateral recumbent) or during the different postures in non-restrained dogs demonstrated that changes in posture had only a minimal influence (</=10% difference) on tidal volume measurements in conscious dogs. Conscious, restrained male beagle dogs given a single intravenous dose of 0.25mg/kg morphine (respiratory depressant) or exposed to a gas mixture containing 8% CO(2) (respiratory stimulant) had values for tidal volume, respiratory rate and minute volume obtained using RIP that were within 7, 3 and 9% of values obtained using a facemask with an attached pneumotachograph. All of the expected changes in tidal volume, respiratory rate and minute volume were also detected in conscious, non-restrained male dogs using RIP following a single intravenous dose of 10mg/kg doxapram (respiratory stimulant), a single intravenous dose of 0.5mg/kg acepromazine (respiratory stimulant) and a single subcutaneous dose of 2mg/kg morphine (respiratory depressant).


CONCLUSIONS
The results of this study demonstrate that RIP is an acceptable method for measuring ventilatory parameters in conscious non-restrained dogs. RIP expands current methodologies in that it allows for continuous monitoring of ventilatory parameters over extended periods of time. This added capability will allow for respiratory monitoring during both the awake and sleep states, which is significant since control of respiratory drive differs between the awake and sleep states and treatment related effects such as sleep apnea or sleep disordered breathing can have adverse health consequences. Combined with cardiovascular telemetry, this methodology will also allow for the combined monitoring of cardiovascular and respiratory parameters in conscious, non-restrained dogs.
Murphy
Dennis J
DJ
Department of Safety Pharmacology, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania, USA. dennis.j.murphy@gsk.com
Renninger
Jonathan P
JP
Schramek
Daniel
D
D000075:Acepromazine / Q000008:administration & dosage / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D003243:Consciousness; D004285:Dogs; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D004315:Doxapram / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D010991:Plethysmography; D011187:Posture; D012119:Respiration; D012131:Respiratory Insufficiency / Q000503:physiopathology; D012143:Respiratory Physiological Phenomena; D056152:Respiratory Rate / Q000187:drug effects; D019141:Respiratory System Agents / Q000008:administration & dosage / Q000494:pharmacology; D013686:Telemetry; D013990:Tidal Volume / Q000187:drug effects
D000701:Analgesics, Opioid; D018492:Dopamine Antagonists; D019141:Respiratory System Agents; D000075:Acepromazine; D009020:Morphine; D004315:Doxapram