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Acute Microinstillation Inhalation Exposure to Sarin Induces Changes in Respiratory Dynamics and Functions in Guinea Pigs

From the United States Army Medical Research Institute of Chemical Defense, Edgewood, MD, USA (MLC, MB, AMS); Walter Reed Army Institute of Research, Silver Spring MD, USA (MMC, RKG, MPN); and Uniformed Services University of the Health Sciences, Bethesda, MD, USA (MPN).

Correspondence: Madhusoodana P. Nambiar, Department of Closed Head Injury, Brain Dysfunction and Blast Injury Division, Walter Reed Army Institute of Research, Silver Spring, MD, USA; e-mail: Madhusoodana.nambiar{at}amedd.army.mil.

This study investigates the toxic effects of sarin on respiratory dynamics following microinstillation inhalation exposure in guinea pigs. Animals are exposed to sarin for 4 minutes, and respiratory functions are monitored at 4 hours and 24 hours by whole-body barometric plethysmography. Data show significant changes in respiratory dynamics and function following sarin exposure. An increase in respiratory frequency is observed at 4 hours post exposure compared with saline controls. Tidal volume and minute volume are also increased in sarin-exposed animals 4 hours after exposure. Peak inspiratory flow increases, whereas peak expiratory flow increases at 4 hours and is erratic following sarin exposure. Animals exposed to sarin show a significant decrease in expiratory time and inspiratory time. End-inspiratory pause is unchanged whereas end-expiratory pause is slightly decreased 24 hours after sarin exposure. These results indicate that inhalation exposure to sarin alters respiratory dynamics and function at 4 hours, with return to normal levels at 24 hours post exposure.

Key Words: acetylcholinesterase • organophosphates • chemical warfare agents • microinstillation • respiratory system • pulmonary injury • barometric plethysmography

International Journal of Toxicology, Vol. 28, No. 5, 436-447 (2009)
DOI: 10.1177/1091581809344879


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