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    Dichlorvos exposure to the Kolliker-fuse nuclei is sufficient but not necessary for OP induced apnea

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    Authors
    Gaspari, Romolo J.
    Dunn, Courtney
    UMass Chan Affiliations
    Department of Emergency Medicine
    Document Type
    Journal Article
    Publication Date
    2013-12-01
    Keywords
    Analysis of Variance
    Animals
    Apnea
    Cholinesterase Inhibitors
    Dichlorvos
    Disease Models, Animal
    Dose-Response Relationship, Drug
    Hemodynamics
    Male
    Organophosphates
    Rats
    Rats, Wistar
    Respiration
    Respiratory Center
    Time Factors
    Emergency Medicine
    Medical Toxicology
    Toxicology
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    Link to Full Text
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844078/
    Abstract
    Patients exposed to organophosphate (OP) compounds demonstrate a central apnea. The Kolliker-fuse nuclei (KF) are cholinergic nuclei in the brainstem involved in central respiratory control. We hypothesize that exposure of the KF is both necessary and sufficient for OP induced central apnea. We performed an animal study of acute OP exposure. Anesthetized and spontaneously breathing Wistar rats (n=24) were exposed to a lethal dose of dichlorvos using three experimental models. Experiment 1 (n=8) involved systemic OP poisoning using subcutaneous (SQ) 2,2-dichlorovinyl dimethyl phosphate (dichlorvos) at 100mg/kg or 3x LD50. Experiment 2 (n=8) involved isolated poisoning of the KF using stereotactic microinjections of dichlorvos (625mug in 50mul) into the KF. Experiment 3 (n=8) involved systemic OP poisoning with isolated protection of the KF using SQ dichlorvos (100mg/kg) and stereotactic microinjections of organophosphatase A (OpdA), an enzyme that degrades dichlorvos. Respiratory and cardiovascular parameters were recorded continuously. Animals were followed post exposure for 1h or until death. There was no difference in respiratory depression between animals with SQ dichlorvos and those with dichlorvos microinjected into the KF. Despite differences in amount of dichlorvos (100mg/kg vs. 1.8mg/kg) and method of exposure (SQ vs. CNS microinjection), 10min following dichlorvos both groups (SQ vs. microinjection respectively) demonstrated a similar percent decrease in respiratory rate (51.5 vs. 72.2), minute ventilation (49.2 vs. 68.8) and volume of expired gas (17.5 vs. 0.0). Animals with OpdA exposure to the KF during systemic OP exposure demonstrated less respiratory depression, compared to SQ dichlorvos alone (p < 0.04). No animals with SQ dichlorvos survived past 25min post exposure, compared to 50% of animals with OpdA exposure to the KF. In conclusion, exposure of the KF is sufficient but not necessary for OP induced apnea. Protection of the KF during systemic OP exposure mitigates OP induced apnea.
    Source
    Neurotoxicology. 2013 Dec;39:132-7. doi: 10.1016/j.neuro.2013.06.009. Epub 2013 Aug 6. Link to article on publisher's site
    DOI
    10.1016/j.neuro.2013.06.009
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/30255
    PubMed ID
    23928117
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.neuro.2013.06.009
    Scopus Count
    Collections
    UMass Chan Faculty and Researcher Publications
    Emergency Medicine Publications

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