The lesion site of organophosphorus-induced central apnea and the effects of antidotes.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Antidotes*/pharmacology ; Sleep Apnea, Central*; Rats ; Animals ; Paraoxon/toxicity ; Rats, Sprague-Dawley ; Neostigmine ; Atropine/pharmacology ; Pralidoxime Compounds/pharmacology ; Pyridines

Organophosphorus poisoning kills individuals by causing central apnea; however, the underlying cause of death remains unclear. Following findings that the pre-Bötzinger complex impairment alone does not account for central apnea, we analyzed the effect of paraoxon on the brainstem-spinal cord preparation, spanning the lower medulla oblongata to phrenic nucleus. Respiratory bursts were recorded by connecting electrodes to the ventral 4th cervical nerve root of excised brainstem-spinal cord preparations obtained from 6-day-old Sprague-Dawley rats. We observed changes in respiratory bursts when paraoxon, neostigmine, atropine, and 2-pyridine aldoxime methiodide were administered via bath application. The percentage of burst extinction in the paraoxon-poisoning group was 50% compared with 0% and 18.2% in the atropine and 2-pyridine aldoxime methiodide treatment groups, respectively. Both treatments notably mitigated the paraoxon-induced reduction in respiratory bursts. In the neostigmine group, similar to paraoxon, bursts stopped in 66.7% of cases but were fully reversed by atropine. This indicates that the primary cause of central apnea is muscarinic receptor-mediated in response to acetylcholine excess. Paraoxon-induced central apnea is hypothesized to result from neural abnormalities within the inferior medulla oblongata to the phrenic nucleus, excluding pre-Bötzinger complex. These antidotes antagonize central apnea, suggesting that they may be beneficial therapeutic agents.
(© 2023. The Author(s).)

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21K16592 Japan Society for the Promotion of Science

0 (Antidotes)
Q9CX8P80JW (Paraoxon)
3982TWQ96G (Neostigmine)
7C0697DR9I (Atropine)
P7MU9UTP52 (pralidoxime)
0 (Pralidoxime Compounds)
0 (Pyridines)

Date Created: 20231122 Date Completed: 20231123 Latest Revision: 20231219

20250114

PMC10663552

10.1038/s41598-023-47745-x

37990100