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 (V{sub E}) and V{sub E} 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{sup -3} (SL, SM, and SH, respectively). V{sub E} and V{sub E} responses to hypercapnia (7% CO{sub 2}) or hypoxia (10% O{sub 2}) were measured by plethysmography at 2 h and 1, 2, and 5 days after VEH or sarin exposure. Total pulmonary resistance (R{sub L}) 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 V{sub E} to similar levels (64 and 69%), SH induced greater respiratory impairment, characterized by lower baseline V{sub E} (30%; P < 0.05), and total loss of the respiratory frequencymore »
- Authors:
-
- Immunology Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive, SE, Albuquerque, NM 87108 (United States)
- Publication Date:
- OSTI Identifier:
- 21180454
- Resource Type:
- Journal Article
- Journal Name:
- Toxicology and Applied Pharmacology
- Additional Journal Information:
- Journal Volume: 232; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2008.07.016; PII: S0041-008X(08)00315-3; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; ACETYLCHOLINE; ANOXIA; CARBON DIOXIDE; DEATH; FAILURES; INHALATION; RATS; TOXICITY
Citation Formats
Jianguo, Zhuang, Xu Fadi, Campen, Matthew J, Cancan, Zhang, Pena-Philippides, Juan C, and Sopori, Mohan L. Inhalation of the nerve gas sarin impairs ventilatory responses to hypercapnia and hypoxia in rats. United States: N. p., 2008.
Web. doi:10.1016/j.taap.2008.07.016.
Jianguo, Zhuang, Xu Fadi, Campen, Matthew J, Cancan, Zhang, Pena-Philippides, Juan C, & Sopori, Mohan L. Inhalation of the nerve gas sarin impairs ventilatory responses to hypercapnia and hypoxia in rats. United States. https://doi.org/10.1016/j.taap.2008.07.016
Jianguo, Zhuang, Xu Fadi, Campen, Matthew J, Cancan, Zhang, Pena-Philippides, Juan C, and Sopori, Mohan L. 2008.
"Inhalation of the nerve gas sarin impairs ventilatory responses to hypercapnia and hypoxia in rats". United States. https://doi.org/10.1016/j.taap.2008.07.016.
@article{osti_21180454,
title = {Inhalation of the nerve gas sarin impairs ventilatory responses to hypercapnia and hypoxia in rats},
author = {Jianguo, Zhuang and Xu Fadi and Campen, Matthew J and Cancan, Zhang and Pena-Philippides, Juan C and Sopori, Mohan L},
abstractNote = {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 (V{sub E}) and V{sub E} 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{sup -3} (SL, SM, and SH, respectively). V{sub E} and V{sub E} responses to hypercapnia (7% CO{sub 2}) or hypoxia (10% O{sub 2}) were measured by plethysmography at 2 h and 1, 2, and 5 days after VEH or sarin exposure. Total pulmonary resistance (R{sub L}) 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 V{sub E} to similar levels (64 and 69%), SH induced greater respiratory impairment, characterized by lower baseline V{sub E} (30%; P < 0.05), and total loss of the respiratory frequency response to hypercapnia and hypoxia. V{sub E} impairment recovered within 1-2 days after sarin exposure; interestingly, SH did not significantly affect baseline R{sub L}. Moreover, sarin induced body tremors that were unrelated to the changes in the V{sub E} responses. Thus, LC{sub 50} sarin causes a reversible impairment of V{sub E} that is not dependent on the sarin-induced body tremors and not associated with changes in R{sub L}.},
doi = {10.1016/j.taap.2008.07.016},
url = {https://www.osti.gov/biblio/21180454},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 232,
place = {United States},
year = {Sat Nov 01 00:00:00 EDT 2008},
month = {Sat Nov 01 00:00:00 EDT 2008}
}