Sarin, a highly toxic
nerve gas, is believed to cause bronchoconstriction and even death primarily through
respiratory failure; however, the mechanism underlying the
respiratory failure is not fully understood. The goals of this study were to ascertain whether
sarin affects baseline ventilation (VE) and VE chemoreflexes as well as airway resistance and, if so, whether these changes are reversible. Four groups of F344 rats were exposed to vehicle (VEH) or
sarin at 2.5, 3.5, and 4.0 mg h m(-3) (SL, SM, and SH, respectively). VE and VE responses to
hypercapnia (7% CO2) or
hypoxia (10% O2) were measured by plethysmography at 2 h and 1, 2, and 5 days after VEH or
sarin exposure. Total pulmonary resistance (RL) also was measured in anesthetized VEH- and SH-exposed animals 2 h after exposure. Our results showed that within 2 h after exposure 11% of the SM- and 52% of the SH- exposed groups died. Although the SM and SH significantly decreased hypercapnic and hypoxic VE to similar levels (64 and 69%), SH induced greater respiratory impairment, characterized by lower baseline VE (30%; P<0.05), and total loss of the respiratory frequency response to
hypercapnia and
hypoxia. VE impairment recovered within 1-2 days after
sarin exposure; interestingly, SH did not significantly affect baseline RL. Moreover,
sarin induced body
tremors that were unrelated to the changes in the VE responses. Thus, LC50
sarin causes a reversible impairment of VE that is not dependent on the
sarin-induced body
tremors and not associated with changes in RL.