title: Inhalation of the nerve gas sarin impairs ventilatory responses to hypercapnia and hypoxia in rats.
abstract: 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.
authors.affiliation: Immunology Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive, SE, Albuquerque, NM 87108 USA.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhuang
authors.forename: Fadi
authors.initials: F
authors.lastname: Xu
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Campen
authors.forename: Cancan
authors.initials: C
authors.lastname: Zhang
authors.forename: Juan C
authors.initials: JC
authors.lastname: Pena-Philippides
authors.forename: Mohan L
authors.initials: ML
authors.lastname: Sopori
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D002619:Chemical Warfare Agents / Q000633:toxicity*; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D019570:Inhalation Exposure; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012119:Respiration / Q000187:drug effects*; D012524:Sarin / Q000633:toxicity*
chemical_list: D002619:Chemical Warfare Agents; D002245:Carbon Dioxide; D012524:Sarin