A novel method for chronic measurement of respiratory function in the conscious monkey.
BACKGROUND
Chronic measurement of respiratory function in the conscious monkey has been limited by the ability to monitor pleural pressure. Previous attempts to measure pleural pressure chronically in conscious animals have involved surgical implantation of pressure-sensitive catheters directly into the pleural cavity. The success of these techniques has been limited by lung damage and/or tissue growth and encapsulation of the pressure-sensitive catheter with damping or loss of the signal. These problems have been eliminated by developing a novel surgical procedure for placement of a pressure-sensitive catheter beneath the pleural surface.


METHODS
A pressure-sensitive catheter (attached to a radiotelemetry transmitter) was surgically implanted beneath the serosal layer of the esophagus within the thoracic cavity. This was accomplished by performing a midline laparotomy, making a small incision in the serosal layer of the esophagus caudal to the diaphragm, and advancing the catheter cranially along the esophagus and beneath the serosal layer into the thoracic cavity. The catheter was secured to the esophageal wall and the telemetry transmitter was sutured to the inner abdominal wall. Respiratory airflow measurements were obtained using a restraint chair equipped with a clear plastic helmet (plethysmograph chamber) that seals around the neck and encloses the head.


RESULTS
The decreases in pleural pressure during inspiration ranged from -5 to -15 mmHg and remained constant for at least 36 weeks following surgery. Intravenous administration of the respiratory depressant morphine, exposure to the respiratory stimulant 8% CO2, and intravenous administration of the bronchoconstrictive agent methacholine verified that this technique was able to detect and quantify ventilatory changes and an increase in airway resistance.


CONCLUSIONS
This novel method for chronic measurement of pleural pressure will facilitate evaluation of the effects of drugs, environmental agents, or disease on respiratory function by allowing repeated measurements of both ventilatory (breathing) patterns and the mechanical properties of the lung in a conscious nonhuman primate.
Murphy
D J
DJ
Department of Safety Assessment, GlaxoSmithKline Pharmaceuticals, King of Prussia, PA, USA. dennis_j_murphy@sbphrd.com
Renninger
J P
JP
Coatney
R W
RW
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D003243:Consciousness / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008252:Macaca fascicularis / Q000502:physiology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D010991:Plethysmography / Q000662:veterinary; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology*; D012129:Respiratory Function Tests / Q000295:instrumentation / Q000662:veterinary; D013686:Telemetry / Q000662:veterinary; D013990:Tidal Volume / Q000187:drug effects / Q000502:physiology
D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D009020:Morphine