Fechtner Linnea, El Ali Mazen, Sattar Abdus, Moore Michael, Strohl Kingman P
Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Louis Stokes Department of Veteran Affairs Medical Center, Cleveland, OH, USA; Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Respir Physiol Neurobiol. 2015 Aug 15;215:20-9. doi: 10.1016/j.resp.2015.04.011. Epub 2015 Apr 30.
We examined the effect of fentanyl on chemoresponsiveness in mouse strains divergent in the expression of spontaneous and post-hypoxic pauses. Frequency and tidal volume were recorded with plethysmography in A/J and C57BL/6J (B6) male mice. Mice selected at random received an intraperitoneal (IP) injection of either saline, low dose fentanyl (LDF = 0.04 mg/kg), or high dose fentanyl (HDF = 0.4 mg/kg) under hypoxia (8% O2) or hyperoxia (100%O2). LDF produced a decrease in frequency during hypoxia in B6, but not A/J, mice. HDF significantly decreased frequency and tidal volume in both strains under hypoxia and hyperoxia (p<0.01); naloxone, an opioid antagonist, reversed this response. The acute administration of fentanyl at any dose did not promote apneas in strains of mice exhibiting regular or irregular respiratory patterns. However, higher doses depressed respiratory frequency in both strains. The B6 mice responded with a depressive response to hypoxia that did not recover with reoxygenation, but did recover with time or naloxone.
我们研究了芬太尼对自发性呼吸暂停和低氧后呼吸暂停表达存在差异的小鼠品系化学敏感性的影响。采用体积描记法记录A/J和C57BL/6J（B6）雄性小鼠的呼吸频率和潮气量。随机选择的小鼠在低氧（8% O₂）或高氧（100% O₂）条件下腹腔注射生理盐水、低剂量芬太尼（LDF = 0.04 mg/kg）或高剂量芬太尼（HDF = 0.4 mg/kg）。低剂量芬太尼使低氧条件下的B6小鼠呼吸频率降低，但对A/J小鼠无此作用。高剂量芬太尼在低氧和高氧条件下均显著降低了两种品系小鼠的呼吸频率和潮气量（p<0.01）；阿片类拮抗剂纳洛酮可逆转这一反应。无论剂量如何，急性给予芬太尼均未促使呈现规则或不规则呼吸模式的小鼠品系出现呼吸暂停。然而，较高剂量会降低两种品系小鼠的呼吸频率。B6小鼠对低氧产生了抑制性反应，复氧后未恢复，但随着时间推移或使用纳洛酮后恢复。
