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

Abstract

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.

Protective efficacy of catalytic bioscavenger, paraoxonase 1 against sarin and soman exposure in guinea pigs

“…Peak inspiratory flow which showed an increase following 508 mg/m 3 sarin exposure at 4 h as reported previously was decreased and was close to normal baseline in PON1 treated animals exposed to 846 mg/m 3 sarin (Fig. 3D) [47]. Peak expiratory flow that tended to increase strongly at 4 h after exposure to 508 mg/m 3 sarin changed much less in PON1 treated animals exposed to sarin (Fig.…”

“…4A and B). At 4 h, T i and T e was increased in PON1 treated animals exposed to 846 mg/m 3 sarin, whereas 508 mg/m 3 sarin exposure resulted in a decrease [47]. End inspiratory pause did not show any significant change in PON1 treated animals exposed to sarin compared to the baseline values (Fig.…”

“…We have reported that microinstillation inhalation exposure to 508 mg/ m 3 sarin results in a significant increase in respiratory frequency, tidal volume, minute ventilation, peak inspiratory flow and expiratory flow at 4 h after exposure [47]. Both human and rabbit serum PON1 treated animals did not show any significant increase in the above respiratory dynamics parameters after exposure to 846 mg/m 3 sarin at 24 h, indicating that PON1 treatment prevents the sarin induced changes in respiratory dynamics.…”

“…3 and 4. Controls with 846 mg/m 3 sarin were not included due to the mortality of these animals, but previous data with 508 mg/m 3 sarin were used for comparison [47]. Respiratory frequency was lower at 4 h after sarin exposure in PON1 treated animals compared to baseline values and was normalized at 24 h (Fig.…”

“…Barometric whole body plethysmography (Buxco Electronics, Inc., Sharon, CT) was used to measure respiratory dynamics in conscious, unrestrained guinea pigs as described previously [45][46][47]. The baseline respiratory parameters were recorded in guinea pigs before exposure and at 4 and 24 h recovery periods after exposure to sarin in PON1 pre-treated animals and the data were analyzed by using BioSystem XE software.…”