The Effects of Experimental Sleep Apnea on Cardiac and Respiratory Functions in 6 and 18 Month Old Dystrophic (mdx) Mice.
The Effects of Experimental Sleep Apnea on Cardiac and Respiratory Functions in 6 and 18 Month Old Dystrophic (mdx) Mice.
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DOI：
10.1371/journal.pone.0147640
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Farkas GA
中科院分区：
文献类型：
--
作者：
Chaudhari MR;Fallavollita JA;Farkas GA
杜氏肌营养不良症（DMD）是一种致命的疾病，超过90%的患者死于呼吸或心脏衰竭。睡眠呼吸暂停和睡眠呼吸障碍（SDB）在多个DMD患者中被注意到，并且所导致的夜间发作性缺氧（EH）不能被排除为心脏和呼吸功能障碍的促成因素。在这项研究中，我们研究了长期的间歇性缺氧，这模拟了睡眠呼吸暂停中的循环缺氧，对DMD小鼠模型（mdx小鼠）的心脏和呼吸功能的影响。由于DMD中睡眠呼吸暂停的严重程度和患病率随着年龄的增长而增加，我们研究了EH对年轻（6个月）和老年（18个月）mdx小鼠的影响。将小鼠暴露于EH（8小时/天，5天/周）或室内空气中12周。我们注意到两个年龄组暴露于EH后左心室（LV）扩张（经胸超声心动图）显著增加，但仅在6个月大的小鼠中观察到LV收缩力降低。随着EH暴露，在18月龄但不是6月龄小鼠的心脏和膈肌中均观察到纤维化（羟脯氨酸）增加。在18个月大的小鼠中，暴露于EH时，未观察到相对膈肌强度（体外）的显著变化。相比之下，暴露于EH的6个月大的小鼠显示出相对膈肌强度的显著增加。EH暴露未导致清醒6月龄mdx小鼠的呼吸参数（气压体积描记法）发生任何显著变化。相比之下，18个月大的mdx小鼠表现出相当大的排便功能障碍，与排便储备减少一致。我们的研究结果强调，睡眠呼吸暂停影响呼吸和心脏功能的肌营养不良症，高血压可以有不同的影响，这两个系统。据我们所知，这是第一个全面的研究，以探讨高血压对心脏和呼吸功能的影响mdx小鼠。
Duchenne muscular dystrophy (DMD) is a fatal disease where over 90% of patients succumb to respiratory or cardiac failure. Sleep apnea and sleep disordered breathing (SDB) are noted in a plurality of DMD patients, and the resulting nocturnal episodic hypoxia (EH) cannot be ruled out as a contributing factor to cardiac and respiratory dysfunction. In this study, we investigated the impact of long-term episodic hypoxia, which mimics the cyclic hypoxia seen in sleep apnea, on cardiac and respiratory function in a murine model of DMD (mdx mice). Since the severity and prevalence of sleep apnea in DMD increases with age, we studied the impact of EH on young (6-month) and on older (18-month) mdx mice. Mice were either exposed for 12 weeks to EH (8 hours/day, 5 days/week) or to room air. We noted a significant increase in left ventricular (LV) dilatation (transthoracic echocardiography) on EH exposure in both age groups, but reduced LV contractility was seen only in 6-month old mice. With EH exposure, an increased fibrosis (hydroxyproline) was noted in both cardiac and diaphragm muscle in 18-month but not 6-month old mice. No significant change in relative diaphragm strength (in-vitro) was noted on EH exposure in 18-month old mice. In contrast, EH exposed 6-month old mice showed a significant increase in relative diaphragm strength. EH exposure did not result in any significant change in ventilatory parameters (barometric plethysmography) in awake 6-month old mdx mice. In contrast, 18-month old mdx mice showed considerable ventilatory dysfunction, consistent with reduced ventilatory reserve. Our findings highlight that sleep apnea impacts respiratory and cardiac function in muscular dystrophy, and that EH can have divergent effects on both systems. To our knowledge, this is the first comprehensive study to investigate the impact of EH on cardiac and respiratory function in mdx mice.