Pulmonary mechanical responses to cholinesterase inhibitor

Area of Science:

• Pulmonary physiology
• Toxicology
• Pharmacology

Background:

• Organophosphate cholinesterase inhibitors like pinacolyl methylphosphonofluoridate (GD) pose significant toxicological risks.
• Understanding the specific pulmonary mechanical effects of GD is crucial for developing effective countermeasures.

Purpose of the Study:

• To investigate the effects of pinacolyl methylphosphonofluoridate (GD) on lung and upper airway mechanics in anesthetized dogs.
• To evaluate the efficacy of atropine in reversing GD-induced pulmonary dysfunction.

Main Methods:

• Measurements of lung static and dynamic compliances, and lung and upper airway resistances in dogs.
• Intravenous administration of GD (2 LD50) followed by atropine (1 mg).
• Analysis of respiratory data using linear regression and Fourier analysis techniques.

Main Results:

• GD significantly increased lung resistance (approx. 20-fold) and decreased lung dynamic compliance (approx. 80%).
• GD induced laryngospasm and altered upper airway resistance, suggesting passive distension.
• Physiological deadspace decreased by up to 65% post-GD.
• Atropine administration rapidly and almost completely reversed all observed GD effects.

Conclusions:

• The primary pulmonary effects of GD in dogs are attributed to smooth muscle constriction throughout the respiratory tract.
• Atropine is a highly effective antidote for mitigating the severe pulmonary consequences of GD exposure.
• GD significantly impairs respiratory system mechanics, highlighting its potential as a chemical warfare agent.