Pulmonary mechanical responses to cholinesterase inhibitor.
Lung static and dynamic compliances, and lung and upper airway resistances were measured in pentobarbital-anesthetized dogs before and after intravenous administration of 2 LD50 of the organophosphate cholinesterase inhibitor pinacolyl methylphosphonofluoridate (GD), followed by 1 mg of atropine 8 min later. Dynamic compliances and resistances were estimated by a linear regression model and by a Fourier analysis technique, with the two methods giving comparable results. GD caused a maximum increase in lung resistance of about 20 times control values, and about an 80% decrease in lung dynamic compliance. Frequency dependence of lung compliance and resistance was increased by GD administration. Following GD administration, upper airway opening pressure increased, indicating the presence of laryngospasm. Upper airway resistance during the latter portion of the breath, when the airway was open, decreased after GD administration, concurrent with the increase in carinal pressure that occurred as the result of increased lung impedance. These results suggest that the GD-induced decrease in upper airway resistance was due to passive distension of the upper airway. Physiological deadspace decreased by a maximum of about 65% following GD administration. Administration of atropine resulted in a prompt and almost complete reversal of all of the GD-induced effects on pulmonary mechanical properties and ventilation. The results of this study suggest that the major pulmonary mechanical effects of GD in the dog are caused by constriction of smooth muscle at different levels of the respiratory tract.
Abbrecht
P H
PH
Department of Physiology, F. Edward Hébert School of Medicine, Uniformed Services, University of the Health Sciences, Bethesda, Maryland 20814.
Kyle
R R
RR
Bryant
H J
HJ
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002245:Carbon Dioxide / Q000097:blood; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004285:Dogs; D008168:Lung / Q000187:drug effects*; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000187:drug effects
D002800:Cholinesterase Inhibitors; D002245:Carbon Dioxide; D001285:Atropine