Effects of sustained hypoxia on sternohyoid and diaphragm muscle during development

Effects of sustained hypoxia on sternohyoid and diaphragm muscle during development
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DOI:
10.1183/09031936.00139512
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发表时间:
2014-04-01
影响因子:
24.3
通讯作者:
O'Halloran, Ken D.
O'Halloran, Ken D.
中科院分区:
医学1区
文献类型:
--
作者:
Carberry, Jayne C.;McMorrow, Clodagh;O'Halloran, Ken D.

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持续缺氧是呼吸系统疾病的主要特征。将Wistar大鼠暴露于持续低氧(环境压力450 mmHg)或常氧条件下1周,在发育过程中的不同时间点,观察持续低氧对呼吸肌形态和功能的影响。在体外评估胸骨舌骨肌和膈肌的收缩和耐力特性。测定肌肉琥珀酸脱氢酶和肌球蛋白重链组成。活性氧在缺氧诱导的肌肉重塑中的作用进行了评估。持续的缺氧增加胸骨舌骨肌的力量和疲劳在早期,但不是晚期的发展,影响后持续恢复正常的氧气。缺氧引起的胸骨舌骨肌疲劳不是由于纤维类型的转变或氧化能力的降低。长期补充超氧化物清除剂tempol没有防止缺氧诱导的胸骨舌骨肌疲劳,这表明与氧化应激无关的机制支持缺氧诱导的胸骨舌骨肌适应不良。持续低氧对膈肌疲劳没有影响,我们认为低氧诱导的气道扩张肌适应不良在发育过程中存在临界窗口。持续缺氧引起的上呼吸道肌肉耐力受损可能持续到晚年。上气道肌肉功能障碍可能对体内咽气道口径的控制产生有害后果。
Sustained hypoxia is a dominant feature of respiratory disease. Despite the clinical significance, the effects of sustained hypoxia on the form and function of respiratory muscle during development are relatively underexplored.Wistar rats were exposed to 1 week of sustained hypoxia (ambient pressure 450 mmHg) or normoxia at various time points during development. Sternohyoid and diaphragm muscle contractile and endurance properties were assessed in vitro. Muscle succinate dehydrogenase and myosin heavy chain composition were determined. The role of reactive oxygen species in hypoxia-induced muscle remodelling was assessed.Sustained hypoxia increased sternohyoid muscle force and fatigue in early but not late development, effects that persisted after return to normoxia. Hypoxia-induced sternohyoid muscle fatigue was not attributable to fibre type transitions or to a decrease in oxidative capacity. Chronic supplementation with the superoxide scavenger tempol did not prevent hypoxia-induced sternohyoid muscle fatigue, suggesting that mechanisms unrelated to oxidative stress underpin hypoxia-induced maladaptation in sternohyoid muscle. Sustained hypoxia had no effect on diaphragm muscle fatigue.We conclude that there are critical windows during development for hypoxia-induced airway dilator muscle maladaptation. Sustained hypoxia-induced impairment of upper airway muscle endurance may persist into later life. Upper airway muscle dysfunction could have deleterious consequences for the control of pharyngeal airway calibre in vivo.