在反复使用芬太尼的反应中,在阿片类药物诱导的呼吸抑制期间,不同的呼吸反应
Karan G Rai1,2,3, Chinwendu U Nwakudu1, Caroline C Szujewski1,3,4
1Department of Medicine, The Section of Emergency Medicine, The University of Chicago, Chicago, Illinois, United States.
概括
重复使用阿片类药物 (ROU) 会改变呼吸控制. 虽然大多数小鼠适应了,但有些人表现出失败的反应,突出了各种结果和中枢神经系统变化影响过量风险.
科学领域:
- 神经科学是一个神经科学.
- 生理学 生理学 生理学
- 药理学 药理学是指药理学的学科.
背景情况:
- 阿片类药物诱导的呼吸系统抑郁 (OIRD) 是芬太尼过量死亡的主要原因.
- 重复使用阿片类药物 (ROU) 对呼吸控制和OIRD的影响尚不清楚.
研究的目的:
- 在小鼠模型中研究ROU如何影响呼吸和Bötzinger前综合体 (preBötC).
- 为了确定反复暴露于芬太尼的生理适应和异质性.
主要方法:
- 开发了一个5天的复发性芬太尼尔给药小鼠模型.
- 检查了呼吸模式,OIRD期间的代谢危机,以及BötC前的活动.
- 在ROU之后,对rhythmogenesis对mu-opioid受体激动症的评估敏感性.
主要成果:
- 最初使用芬太尼在OIRD期间引起了代谢危机.
- 到第5天,77%的小鼠表现出适应性呼吸反应,并在OIRD期间改善了通风与氧气消耗的匹配.
- 少数小鼠未能产生适应性反应,这表明异质的结果.
- ROU 降低了 preBötC 对 mu-阿片类受体激素的敏感性,这表明中心适应.
结论:
- 在OIRD期间,ROU会诱导生理变化,这些变化通常会改善OIRD期间的通风和氧化.
- 不同的呼吸系统反应和潜在的中央适应有助于变化的过量敏感性.
- 研究结果阐明了阿片类药物使用者的耐受性和易感性的生理基础.
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