Acute microinstillation inhalation exposure to soman induces changes in respiratory dynamics and functions in guinea pigs

Abstract

We investigated the toxic effects of the chemical warfare nerve agent (CWNA) soman (GD) on the respiratory dynamics of guinea pigs following microinstillation inhalation exposure. Male Hartley guinea pigs were exposed to 841 mg/m³ of GD or saline for 4 min. At 24 and 48 h post GD exposure, respiratory dynamics and functions were monitored for 75 min after 1 h of stabilization in a barometric whole-body plethysmograph. GD-exposed animals showed a significant increase in respiratory frequency (RF) at 24 h postexposure compared to saline controls. The 24-h tidal volume (TV) increased in GD-exposed animals during the last 45 min of the 75-min monitoring period in the barometric whole-body plethysmograph. Minute ventilation also increased significantly at 24 h post GD exposure. The peak inspiratory flow (PIF) increased, whereas peak expiratory flow (PEF) decreased at 24 h and was erratic following GD exposure. Animals exposed to GD showed a significant decrease in expiratory (Te) and inspiratory time (Ti). Although end inspiratory pause (EIP) and end expiratory pause (EEP) were both decreased 24 h post GD exposure, EEP was more evident. Pause (P) decreased equally during the 75-min recording in GD-exposed animals, whereas the pseudo lung resistance (Penh) decreased initially during the monitoring period but was near control levels at the end of the 75-min period. The 48-h respiratory dynamics and function parameter were lower than 24 post GD exposures. These results indicate that inhalation exposure to soman in guinea pigs alters respiratory dynamics and function at 24 and 48 h postexposure.

Key words::

• acetylcholinesterase
• organophosphates
• soman
• microinstillation;
• respiratory system
• pulmonary injury
• chemical warfare nerve agents
• guinea pig barometric plethysmography
• lung resistance

Acknowledgments

We thank the Medical Research and Materiel Command of the U.S. Army and Defense of Threat Reduction Agency for funding. The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Army, Navy, or Department of Defense.

Declaration of interest: The authors report no conflicts of interest.