Journal of applied physiology
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Acute intermittent hypoxia (AIH) elicits a form of spinal respiratory plasticity known as phrenic long-term facilitation (pLTF). pLTF requires spinal serotonin receptor-2 activation, the synthesis of new brain-derived neurotrophic factor (BDNF), and the activation of its high-affinity receptor tyrosine kinase, TrkB. Spinal adenosine 2A receptor activation elicits a distinct pathway to phrenic motor facilitation (pMF); this BDNF synthesis-independent pathway instead requires new synthesis of an immature TrkB isoform. Since hypoxia increases extracellular adenosine levels, we tested the hypothesis that new synthesis of TrkB and BDNF contribute to AIH-induced pLTF. ⋯ Thus, AIH-induced pLTF requires MEK/ERK (not PI3K/AKT) signaling pathways. When U0126 was injected post-AIH, pLTF development was halted but not reversed, suggesting that ERK is critical for the development but not maintenance of pLTF. Thus, there are clear mechanistic distinctions between AIH-induced pLTF (i.e., BDNF synthesis and MEK/ERK dependent) versus adenosine 2A receptor-induced pMF (i.e., TrkB synthesis and PI3K/Akt dependent).
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Randomized Controlled Trial
Exercise intensity typical of mountain climbing does not exacerbate acute mountain sickness in normobaric hypoxia.
Physical exertion is thought to exacerbate acute mountain sickness (AMS). In this prospective, randomized, crossover trial, we investigated whether moderate exercise worsens AMS in normobaric hypoxia (12% oxygen, equivalent to 4,500 m). Sixteen subjects were exposed to altitude twice: once with exercise [3 × 45 min within the first 4 h on a bicycle ergometer at 50% of their altitude-specific maximal workload (maximal oxygen uptake)], and once without. ⋯ After exercise, the increase in ventilation persisted for several hours and was associated with similar levels of capillary and cerebral oxygenation at the exercise and rest day. We conclude that moderate exercise at ~50% maximal oxygen uptake does not increase AMS in normobaric hypoxia. These data do not exclude that considerably higher exercise intensities exacerbate AMS.
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Clinical Trial
Heliox increases quadriceps muscle oxygen delivery during exercise in COPD patients with and without dynamic hyperinflation.
Some reports suggest that heliox breathing during exercise may improve peripheral muscle oxygen availability in patients with chronic obstructive pulmonary disease (COPD). Besides COPD patients who dynamically hyperinflate during exercise (hyperinflators), there are patients who do not hyperinflate (non-hyperinflators). As heliox breathing may differently affect cardiac output in hyperinflators (by increasing preload and decreasing afterload of both ventricles) and non-hyperinflators (by increasing venous return) during exercise, it was reasoned that heliox administration would improve peripheral muscle oxygen delivery possibly by different mechanisms in those two COPD categories. ⋯ In hyperinflators, heliox reduced end-expiratory chest wall volume and diaphragmatic activity, and increased arterial oxygen content (by 17.8 ± 2.5 ml/l), whereas, in non-hyperinflators, heliox reduced peak-expiratory gastric pressure and increased systemic vascular conductance (by 11.0 ± 2.8 ml·min(-1)·mmHg(-1)). Quadriceps muscle blood flow and oxygen delivery significantly improved during heliox compared with room air by a comparable magnitude (in hyperinflators by 6.1 ± 1.3 ml·min(-1)·100 g(-1) and 1.3 ± 0.3 ml O(2)·min(-1)·100 g(-1), and in non-hyperinflators by 7.2 ± 1.6 ml·min(-1)·100 g(-1) and 1.6 ± 0.3 ml O(2)·min(-1)·100 g(-1), respectively). Despite similar increase in locomotor muscle oxygen delivery with heliox in both groups, the mechanisms of such improvements were different: 1) in hyperinflators, heliox increased arterial oxygen content and quadriceps blood flow at similar cardiac output, whereas 2) in non-hyperinflators, heliox improved central hemodynamics and increased systemic vascular conductance and quadriceps blood flow at similar arterial oxygen content.
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Electrical impedance tomography (EIT) is a functional imaging modality capable of tracing continuously regional pulmonary gas volume changes. The aim of our study was to determine if EIT was able to assess spatial and temporal heterogeneity of ventilation during pulmonary function testing in 14 young (37 ± 10 yr, mean age ± SD) and 12 elderly (71 ± 9 yr) subjects without lung disease and in 33 patients with chronic obstructive pulmonary disease (71 ± 9 yr). EIT and spirometry examinations were performed during tidal breathing and a forced vital capacity (FVC) maneuver preceded by full inspiration to total lung capacity. ⋯ Receiver-operating characteristics curves showed that CV of regional IVC, FVC, FEV(1), and V(T) discriminated the young and elderly subjects from the patients. Frequency distributions of pixel FEV(1)/FVC, t(25), t(50), t(75), and t(90) identified the highest ventilation heterogeneity in patients but distinguished also the healthy young from the elderly subjects. These results indicate that EIT may provide additional information during pulmonary function testing and identify pathologic and age-related spatial and temporal heterogeneity of regional lung function.
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We sought to determine the influence of sympathoexcitation on dynamic cerebral autoregulation (CA), cerebrovascular reactivity, and ventilatory control in humans at high altitude (HA). At sea level (SL) and following 3-10 days at HA (5,050 m), we measured arterial blood gases, ventilation, arterial pressure, and middle cerebral blood velocity (MCAv) before and after combined α- and β-adrenergic blockade. Dynamic CA was quantified using transfer function analysis. ⋯ Despite elevations in MCAv reactivity to hypercapnia at HA, blockade reduced (P < 0.05) it comparably at SL and HA, effects we attributed to the hypotension and/or abolition of the hypercapnic-induced increase in MAP. With the exception of dynamic CA, we provide evidence of a redundant role of sympathetic nerve activity as a direct mechanism underlying changes in cerebrovascular reactivity and ventilatory control following partial acclimatization to HA. These findings have implications for our understanding of CBF function in the context of pathologies associated with sympathoexcitation and hypoxemia.