Department of Pharmacology, Biomedical Center Martin, Comenius University Jessenius Faculty of Medicine in Martin, Mala Hora 4C 11161, 036 01 Martin, Slovakia.
Pediatric Department, Comenius University Jessenius Faculty of Medicine in Martin and Martin University Hospital, Kollarova 2, 036 59 Martin, Slovakia.
J Pharmacol Sci. 2020 Apr;142(4):165-171. doi: 10.1016/j.jphs.2020.01.005. Epub 2020 Jan 22.
There is no direct evidence for the exact cilia-inhibitory effects of opioids, which are generally used to achieve general anesthesia in combination with other anesthetic drugs. These are the reasons, why we analysed direct concentration-dependent or systemic effects of anesthetics (propofol, sufentanil, and midazolam) at a recommended doses administered individually or simultaneously on the tracheal ciliary beat frequency (CBF) in in vitro experimental conditions. Brush biopsy technique was used to remove the tracheal epithelia of guinea pigs for microscopy evaluation of ciliary beating monitored by high-speed video camera and analysed by Ciliary Analysis software. The tracheal CBF was significantly lower in the presence of sufentanil (10 mol/L) than in the control group; similarly for midazolam-sufentanil (10 - 10 mol/L), as well as for midazolam-propofol (10 and 10 mol/L) combinations. The fact that concurrent administration of benzodiazepine significantly increased the risk of sufentanil-induced cilia-inhibition was pharmacologically confirmed using GABA receptor antagonist, bicuculline methiodide. The benefit of propofol on the potent cilia-inhibitory effect achieved by benzodiazepine-opioid combination was non-significant. We highlight the pharmacodynamics interaction between anesthetic drugs mediated via GABA receptor with negative impact on the CBF in a respiratory epithelium under experimental condition rather than the effect of individual anesthetic.
没有直接证据表明阿片类药物具有确切的纤毛抑制作用,这些药物通常与其他麻醉药物联合使用以实现全身麻醉。这就是为什么我们在体外实验条件下分析了推荐剂量的麻醉剂(异丙酚、舒芬太尼和咪达唑仑)的直接浓度依赖性或全身效应,这些麻醉剂单独或同时用于气管纤毛拍打频率(CBF)。采用刷活检技术从豚鼠的气管上皮中去除,使用高速摄像机监测纤毛的运动并通过纤毛分析软件进行分析。与对照组相比,舒芬太尼(10 摩尔/升)存在时气管 CBF 显著降低;同样对于咪达唑仑-舒芬太尼(10-10 摩尔/升)以及咪达唑仑-异丙酚(10 和 10 摩尔/升)组合也是如此。使用 GABA 受体拮抗剂,甲碘化荷包牡丹碱,从药理学上证实了苯二氮䓬类药物的同时给药显著增加了舒芬太尼引起的纤毛抑制的风险。异丙酚对苯二氮䓬类药物-阿片类药物联合用药产生的纤毛抑制作用的有益影响并不显著。我们强调了麻醉药物通过 GABA 受体介导的药效学相互作用对实验条件下呼吸上皮中 CBF 的负面影响,而不是单个麻醉药物的作用。