UCD School of Medicine and Medical Science, Room C228, Health Sciences Centre, University College Dublin, Belfield, Dublin 4, Ireland.
Am J Respir Cell Mol Biol. 2010 Jun;42(6):725-31. doi: 10.1165/rcmb.2009-0160OC. Epub 2009 Jul 27.
Obstructive sleep apnea is a common disorder associated with upper airway muscle dysfunction. Agents that improve respiratory muscle performance may be useful as an adjunct therapy. The aim of this study was to examine the effects of antioxidants on rat pharyngeal dilator muscle performance. Adult male Wistar rats were killed humanely and isometric contractile properties of isolated sternohyoid muscle strips were examined in physiological salt solution at 35 degrees C in vitro. Muscle strips were incubated in tissue baths under hyperoxic (95%O(2)/5%CO(2)) or hypoxic (95%N(2)/5%CO(2)) conditions in the absence (control) or presence of the antioxidants: N-acetylcysteine (10 mM), Tiron (10 mM), or Tempol (10 mM). Force-frequency relationship was determined in response to supramaximal stimulation (10-100 Hz in increments of 10-20 Hz, train duration: 300 ms). Isometric force was also recorded during repetitive muscle stimulation (40 Hz, 300 ms every 2 s for 2 min). Under hyperoxic conditions, Tiron and Tempol, but not N-acetylcysteine, significantly increased sternohyoid muscle force and caused a left-shift in the force-frequency relationship. In addition, Tempol had a significant positive inotropic effect over the initial 90 seconds of repeated muscle activation. Hypoxia caused a significant decrease in sternohyoid muscle force. Under hypoxic conditions, Tempol-incubated muscles generated significantly higher forces compared with control muscles and showed improved performance in the early phase of the fatigue trial. This study illustrates that superoxide scavengers increase upper airway muscle force and that this effect persists under hypoxic conditions. We conclude that antioxidant treatment may be beneficial as a therapy in obstructive sleep apnea.
阻塞性睡眠呼吸暂停是一种与上气道肌肉功能障碍相关的常见疾病。改善呼吸肌功能的药物可能作为辅助治疗方法有用。本研究的目的是研究抗氧化剂对大鼠咽扩肌性能的影响。雄性 Wistar 大鼠在人道处死，在 35°C 体外生理盐溶液中，使用等长收缩特性检测分离的胸锁乳突肌肌条。在不存在（对照）或存在抗氧化剂（N-乙酰半胱氨酸（10mM）、Tiron（10mM）或 Tempol（10mM））的情况下，肌条在高氧（95%O2/5%CO2）或低氧（95%N2/5%CO2）条件下孵育于组织浴中。在超极化刺激（10-100Hz，每隔 10-20Hz 增加一次，刺激持续时间：300ms）下测定力频率关系。在重复肌肉刺激（40Hz，每 2s 刺激 300ms，持续 2min）期间也记录等长力。在高氧条件下，Tiron 和 Tempol 但不是 N-乙酰半胱氨酸显著增加胸锁乳突肌的力，并使力频率关系向左移位。此外，Tempol 在重复肌肉激活的最初 90 秒内具有显著的正性肌力作用。低氧导致胸锁乳突肌力显著降低。在低氧条件下，Tempol 孵育的肌肉产生的力明显高于对照肌肉，并且在疲劳试验的早期阶段表现出更好的性能。本研究表明，超氧化物清除剂增加上气道肌肉的力，并且该效应在低氧条件下持续存在。我们得出结论，抗氧化剂治疗可能作为阻塞性睡眠呼吸暂停的治疗方法有益。
