Diaphragm abnormalities in heart failure and aging: mechanisms and integration of cardiovascular and respiratory pathophysiology.
Diaphragm abnormalities in heart failure and aging: mechanisms and integration of cardiovascular and respiratory pathophysiology.
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DOI：
10.1007/s10741-016-9549-4
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发表时间：
2017-03
影响因子：
4.6
通讯作者：
Ferreira LF
中科院分区：
文献类型：
--
作者：
Kelley RC;Ferreira LF
吸气功能对于肺泡通气和促进气道清除的呼气行为（例如咳嗽和打喷嚏）至关重要。目前的证据表明，呼吸功能障碍发生在健康老龄化过程中，并且因慢性心力衰竭（CHF）而加剧。这种吸气功能障碍是导致 CHF 以及心血管和肺部病理生理学老化的关键因素，包括： i) 气道清除功能受损和肺炎易感性； ii) 在体力活动期间无法维持通风； iii) 浅呼吸模式限制了肺泡通气和气体交换； iv) 引起心律失常和组织血管收缩的交感神经激活。膈肌是主要的吸气肌，因此，其神经肌肉的完整性是吸气功能充分性的主要决定因素。动物和细胞模型中的机制工作揭示了可能导致慢性心力衰竭和衰老中隔膜神经肌肉异常的特定因素。这些包括膈神经和神经肌肉接头的改变以及内在的肌细胞异常，例如收缩蛋白的数量和质量的变化、加速的纤维萎缩以及纤维类型分布的变化。 CHF、衰老或存在衰老的 CHF 会扰乱循环因子（例如细胞因子和血管紧张素 II）的动态以及涉及鞘脂、活性氧和蛋白水解途径的细胞信号传导，从而导致前面列出的异常。基于运动的康复结合针对本文所述途径的药物治疗有望治疗 CHF 和衰老引起的膈肌异常和吸气肌功能障碍。
Inspiratory function is essential for alveolar ventilation and expulsive behaviors that promote airway clearance (e.g., coughing and sneezing). Current evidence demonstrates that inspiratory dysfunction occurs during healthy aging and is accentuated by chronic heart failure (CHF). This inspiratory dysfunction contributes to key aspects of CHF and aging cardiovascular and pulmonary pathophysiology including: i) impaired airway clearance and predisposition to pneumonia; ii) inability to sustain ventilation during physical activity; iii) shallow breathing pattern that limits alveolar ventilation and gas exchange; and iv) sympathetic activation that causes cardiac arrhythmias and tissue vasoconstriction. The diaphragm is the primary inspiratory muscle, hence, its neuromuscular integrity is a main determinant of the adequacy of inspiratory function. Mechanistic work within animal and cellular models has revealed specific factors that may be responsible for diaphragm neuromuscular abnormalities in CHF and aging. These include phrenic nerve and neuromuscular junction alterations as well as intrinsic myocyte abnormalities, such as changes in the quantity and quality of contractile proteins, accelerated fiber atrophy, and shifts in fiber type distribution. CHF, aging, or CHF in the presence of aging disturbs the dynamics of circulating factors (e.g., cytokines and angiotensin II) and cell signaling involving sphingolipids, reactive oxygen species, and proteolytic pathways, thus leading to the previously listed abnormalities. Exercise-based rehabilitation combined with pharmacological therapies targeting the pathways reviewed herein hold promise to treat diaphragm abnormalities and inspiratory muscle dysfunction in CHF and aging.