Journal of applied physiology
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Muscle dysfunction often occurs in patients with chronic obstructive pulmonary disease (COPD) and may involve both respiratory and locomotor (peripheral) muscles. The loss of strength and/or endurance in the former can lead to ventilatory insufficiency, whereas in the latter it limits exercise capacity and activities of daily life. Muscle dysfunction is the consequence of complex interactions between local and systemic factors, frequently coexisting in COPD patients. ⋯ Under all these circumstances, protein metabolism imbalance, oxidative stress, inflammatory events, as well as muscle injury may occur, determining the final structure and modulating the function of different muscle groups. Respiratory muscles show signs of injury as well as an increase in several elements involved in aerobic metabolism (proportion of type I fibers, capillary density, and aerobic enzyme activity) whereas limb muscles exhibit a loss of the same elements, injury, and a reduction in fiber size. In the present review we examine the current state of the art of the pathophysiology of muscle dysfunction in COPD.
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The role of angiogenesis factors in skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD) is unknown. The first objective of this study was to assess various pro- and antiangiogenic factor and receptor expressions in the vastus lateralis muscles of control subjects and COPD patients. Preliminary inquiries revealed that angiopoietin-2 (ANGPT2) is overexpressed in limb muscles of COPD patients. ⋯ Immunoblotting confirmed that ANGPT2 protein levels were significantly greater in muscles of COPD patients compared with control subjects. ANGPT2 expression was induced by interferon-γ and -β and by hydrogen peroxide, but not by tumor necrosis factor. We conclude that upregulation of ANGPT2 expression in vastus lateralis muscles of COPD patients is likely due to oxidative stress and represents a positive adaptive response aimed at facilitating myogenesis and angiogenesis.
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Chronic obstructive pulmonary disease (COPD) is a debilitating disease caused by parenchymal damage and irreversible airflow limitation. In addition to lung dysfunction, patients with COPD develop weight loss, malnutrition, poor exercise performance, and skeletal muscle atrophy. The latter has been attributed to an imbalance between muscle protein synthesis and protein degradation. ⋯ Pilot experiments on vastus lateralis muscle samples suggest that the autophagy-lysosome system is induced in COPD patients compared with control subjects. In this review, we summarize recent progress related to molecular structure, regulation, and roles of the autophagy-lysosome pathway in normal and diseased skeletal muscles. We also speculate about regulation and functional importance of this system in skeletal muscle dysfunction in COPD patients.
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Randomized Controlled Trial Comparative Study
Mechanisms of nasal high flow on ventilation during wakefulness and sleep.
Nasal high flow (NHF) has been shown to increase expiratory pressure and reduce respiratory rate but the mechanisms involved remain unclear. Ten healthy participants [age, 22 ± 2 yr; body mass index (BMI), 24 ± 2 kg/m(2)] were recruited to determine ventilatory responses to NHF of air at 37°C and fully saturated with water. We conducted a randomized, controlled, cross-over study consisting of four separate ∼60-min visits, each 1 wk apart, to determine the effect of NHF on ventilation during wakefulness (NHF at 0, 15, 30, and 45 liters/min) and sleep (NHF at 0, 15, and 30 liters/min). ⋯ In the nasal cavity model, NHF increased expiratory but decreased inspiratory resistance depending on both the cannula size and the expiratory flow rate. The mechanisms of action for NHF differ from those of CPAP and are sleep/wake-state dependent. NHF may be utilized to increase tidal breathing during wakefulness and to relieve respiratory loads during sleep.
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Randomized Controlled Trial
Worsening of central sleep apnea at high altitude--a role for cerebrovascular function.
Although periodic breathing during sleep at high altitude occurs almost universally, the likely mechanisms and independent effects of altitude and acclimatization have not been clearly reported. Data from 2005 demonstrated a significant relationship between decline in cerebral blood flow (CBF) at sleep onset and subsequent severity of central sleep apnea that night. We suspected that CBF would decline during partial acclimatization. ⋯ Over 10 days, the increases resolved and AHI worsened. During sleep at high altitude large oscillations in mean CBF velocity (CBFv) occurred, which were 35% higher initially (peak CBFv = 96 cm/s vs. peak CBFv = 71 cm/s) than at days 12-15. Our novel findings suggest that elevations in CBF and its reactivity to CO(2) upon initial ascent to high altitude may provide a protective effect on the development of periodic breathing during sleep (likely via moderating changes in central Pco2).