A Comparison of the Effects of Sarin and Succinylcholine on Respiratory Parameters in Anesthetized Domestic Swine

Duncan, Erica; Conley, John D.; Grychowski, Kristen D.; Conley, Seamus A.; Lundy, Paul M.; Hamilton, Mary G.; Sawyer, Thomas W.

doi:10.1093/milmed/166.4.322

Cited by 10 publications

(1 citation statement)

References 7 publications

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“…A simulated anthrax letter scenario was developed and swine were used to investigate deposition of aerosolized BG spores in the lungs. Swine have been used extensively in biomedical research because of the anatomical and physiological similarity between swine and human respiratory systems (Conley et al 2001;Weiskopf et al, 1992;Nyberg et al, 1995), and on countermeasures against chemical warfare agents (Nelson et al, 2002;Duncan et al, 2002;Chilcott et al, 2003;Chilcott et al, 2005a;Chilcott et al, 2005b;Hamilton et al, 2004;Lundy et al, 2005). Functional studies of the airway, including neurochemical anatomy and smooth muscle function, make swine useful in models of acute respiratory distress syndrome and asthma, and the neonatal development of the lungs and airways is useful for extrapolation to humans (Brown & Terris, 1996).…”

Section: Introductionmentioning

confidence: 99%

Pulmonary Deposition of AerosolizedBacillus Atrophaeusin a Swine Model Due to Exposure from a Simulated Anthrax Letter Incident

Duncan¹,

Kournikakis²,

Ho³

et al. 2009

Inhalation Toxicology

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Dry anthrax spore powder is readily disseminated as an aerosol and it is possible that passive dispersion when opening a letter containing anthrax spores may result in lethal doses to humans. The specific aim of this study was to quantify the respirable aerosol hazard associated with opening an envelope/letter contaminated with a dry spore powder of the biological pathogen anthrax in a typical office environment. An envelope containing a letter contaminated with 1.0 g of dry Bacillus atrophaeus (BG) spores (pathogen simulant) was opened in the presence of an unrestrained swine model. Aerosolized spores were detected in the room in seconds and peak concentrations occurred by three minutes. The swine, located approximately 1.5 m from the source, was exposed to the aerosol for 28 min following the letter opening event and then moved to a clean room for 30 min. A necropsy was completed to determine the extent of in vivo spore deposition in the lungs. The median number of viable colony forming units (CFU) measured in the combined right and left lung was 21,200: the average mass of both lungs was 283 g. In excess of 100 CFU per gram of lung tissue was found at sites within the anterior, intermediate and posterior lobes. The results of this study confirmed that opening an envelope containing spores generated an aerosol spanning the respirable particle size range of 1-10 µm, and that normal respiration of swine led to spore deposition throughout the lungs. The observed deposition of spores in the lungs of the swine is within the LD 50 range of 2,500-55,000 estimated for humans for inhaled anthrax. Thus, there would appear to be a significant health risk to those individuals exposed to anthrax spores when opening a contaminated envelope.

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Section: Introductionmentioning

confidence: 99%

Pulmonary Deposition of AerosolizedBacillus Atrophaeusin a Swine Model Due to Exposure from a Simulated Anthrax Letter Incident

Duncan¹,

Kournikakis²,

Ho³

et al. 2009

Inhalation Toxicology

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Organophosphorus poisoning in animals and enzymatic antidotes

Poirier

Jacquet

Plener

et al. 2018

Environ Sci Pollut Res

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Organophosphorus compounds (OPs) are neurotoxic molecules developed as pesticides and chemical warfare nerve agents (CWNAs). Most of them are covalent inhibitors of acetylcholinesterase (AChE), a key enzyme in nervous systems, and are therefore responsible for numerous poisonings around the world. Many animal models have been studied over the years in order to decipher the toxicity of OPs and to provide insights for therapeutic and decontamination purposes. Environmental impact on wild animal species has been analyzed to understand the consequences of OP uses in agriculture. In complement, various laboratory models, from invertebrates to aquatic organisms, rodents and primates, have been chosen to study chronic and acute toxicity as well as neurobehavioral impact, immune response, developmental disruption, and other pathological signs. Several decontamination approaches were developed to counteract the poisoning effects of OPs. Among these, enzyme-based strategies are particularly attractive as they allow efficient external decontamination without toxicity or environmental impact and may be of interest for treatment. Approaches using bioscavengers for prophylaxis, treatment, and external decontamination are emphasized and their potential is discussed in the light of toxicological observations from various animal models. The relevance of animal models, regarding their cholinergic system and the abundance of naturally protecting enzymes, is also discussed for better extrapolation of results to human.

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Inhalation of the nerve gas sarin impairs ventilatory responses to hypercapnia and hypoxia in rats

Zhuang¹,

Xu²,

Campen³

et al. 2008

Toxicology and Applied Pharmacology

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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 E ) and V 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 −3 (SL, SM, and SH, respectively). V E and V E responses to hypercapnia (7% CO 2 ) or hypoxia (10% O 2 ) were measured by plethysmography at 2 h and 1, 2, and 5 days after VEH or sarin exposure. Total pulmonary resistance (R L ) also was measured in anesthetized VEH-and SHexposed 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 E to similar levels (64 and 69%), SH induced greater respiratory impairment, characterized by lower baseline V E (30%; P < 0.05), and total loss of the respiratory frequency response to hypercapnia and hypoxia. V E impairment recovered within 1-2 days after sarin exposure; interestingly, SH did not significantly affect baseline R L . Moreover, sarin induced body tremors that were unrelated to the changes in the V E responses. Thus, LC 50 sarin causes a reversible impairment of V E that is not dependent on the sarin-induced body tremors and not associated with changes in R L .

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A Comparison of the Effects of Sarin and Succinylcholine on Respiratory Parameters in Anesthetized Domestic Swine

Cited by 10 publications

References 7 publications

Pulmonary Deposition of AerosolizedBacillus Atrophaeusin a Swine Model Due to Exposure from a Simulated Anthrax Letter Incident

Pulmonary Deposition of AerosolizedBacillus Atrophaeusin a Swine Model Due to Exposure from a Simulated Anthrax Letter Incident

Organophosphorus poisoning in animals and enzymatic antidotes

Inhalation of the nerve gas sarin impairs ventilatory responses to hypercapnia and hypoxia in rats

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