Department of Emergency Medicine, Sapporo Medical University Hospital, Minami1-jo nishi 16 Chome 291, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.
Sci Rep. 2020 Sep 28;10(1):15834. doi: 10.1038/s41598-020-73003-5.
Whether central apnoea or hypopnoea can be induced by organophosphorus poisoning remains unknown to date. By using the acute brainstem slice method and multi-electrode array system, we established a paraoxon (a typical acetylcholinesterase inhibitor) poisoning model to investigate the time-dependent changes in respiratory burst amplitudes of the pre-Bötzinger complex (respiratory rhythm generator). We then determined whether pralidoxime or atropine, which are antidotes of paraoxon, could counteract the effects of paraoxon. Herein, we showed that paraoxon significantly decreased the respiratory burst amplitude of the pre-Bötzinger complex (p < 0.05). Moreover, pralidoxime and atropine could suppress the decrease in amplitude by paraoxon (p < 0.05). Paraoxon directly impaired the pre-Bötzinger complex, and the findings implied that this impairment caused central apnoea or hypopnoea. Pralidoxime and atropine could therapeutically attenuate the impairment. This study is the first to prove the usefulness of the multi-electrode array method for electrophysiological and toxicological studies in the mammalian brainstem.
目前尚不清楚有机磷中毒是否会导致中枢性呼吸暂停或呼吸不足。通过使用急性脑片方法和多电极阵列系统,我们建立了一个对氧磷(一种典型的乙酰胆碱酯酶抑制剂)中毒模型,以研究呼吸节律发生器前包钦格复合体(pre-Bötzinger complex)呼吸爆发幅度的时间依赖性变化。然后,我们确定了对氧磷的解毒剂解磷定或阿托品是否可以对抗对氧磷的作用。在这里,我们表明对氧磷显著降低了前包钦格复合体的呼吸爆发幅度(p<0.05)。此外,解磷定和阿托品可以抑制对氧磷引起的幅度降低(p<0.05)。对氧磷直接损害了前包钦格复合体,这一发现表明这种损害导致了中枢性呼吸暂停或呼吸不足。解磷定和阿托品可以治疗性地减轻这种损害。这项研究首次证明了多电极阵列方法在哺乳动物脑干电生理和毒理学研究中的有效性。