Journal of applied physiology
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Exercise enhances branched-chain amino acid (BCAA) catabolism, and BCAA supplementation influences exercise metabolism. However, it remains controversial whether BCAA supplementation improves exercise endurance, and unknown whether the exercise endurance effect of BCAA supplementation requires catabolism of these amino acids. Therefore, we examined exercise capacity and intermediary metabolism in skeletal muscle of knockout (KO) mice of mitochondrial branched-chain aminotransferase (BCATm), which catalyzes the first step of BCAA catabolism. ⋯ While muscle ATP concentration tended to be lower, muscle IMP concentration was sevenfold higher in KO compared with WT mice after a brief bout of exercise, suggesting elevated ammonia in KO is derived from the purine nucleotide cycle. These data suggest that disruption of BCAA transamination causes impaired malate/aspartate shuttle, thereby resulting in decreased alanine and glutamine formation, as well as increases in lactate-to-pyruvate ratio and ammonia in skeletal muscle. Thus BCAA metabolism may regulate exercise capacity in mice.
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Airway exposure to zinc dust and zinc-containing ambient particulates can cause symptoms of airway irritation and inflammation, but the underlying molecular and cellular mechanisms are largely unknown. Transient receptor potential A1 (TRPA1) is selectively expressed in a subpopulation of pulmonary C-fiber afferents and has been considered as a major irritant sensor in the lung and airways. ⋯ In addition, our study showed that two other heavy metals, cadmium and copper, also stimulated pulmonary sensory neurons via a direct activation of TRPA1. In summary, our results suggest that activation of TRPA1 in pulmonary C-fiber sensory nerves may contribute to the respiratory toxicity induced by airway exposure to these three heavy metals.
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Continuous estimates of dynamic cerebral autoregulation during transient hypocapnia and hypercapnia.
Dynamic cerebral autoregulation (CA) is the transient response of cerebral blood flow (CBF) to rapid blood pressure changes: it improves in hypocapnia and becomes impaired during hypercapnia. Batch-processing techniques have mostly been used to measure CA, providing a single estimate for an entire recording. A new approach to increase the temporal resolution of dynamic CA parameters was applied to transient hypercapnia and hypocapnia to describe the time-varying properties of dynamic CA during these conditions. ⋯ Hyperventilation led to a marked decrease in ET(CO(2)) (-7.2 +/- 4.1 mmHg, P < 0.001). Unexpectedly, CA efficiency dropped significantly with the inception of the metronome-controlled hyperventilation, but, after approximately 30 s, the ARI increased gradually to show a maximum change of 5.7 +/- 2.9 and 5.3 +/- 3.0 for the right and left MCA, respectively (P < 0.001). These results confirm the potential of continuous estimates of dynamic CA to improve our understanding of human cerebrovascular physiology and represent a promising new approach to improve the sensitivity of clinical applications of dynamic CA modeling.
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Comparative Study
Esophageal pressures in acute lung injury: do they represent artifact or useful information about transpulmonary pressure, chest wall mechanics, and lung stress?
Acute lung injury can be worsened by inappropriate mechanical ventilation, and numerous experimental studies suggest that ventilator-induced lung injury is increased by excessive lung inflation at end inspiration or inadequate lung inflation at end expiration. Lung inflation depends not only on airway pressures from the ventilator but, also, pleural pressure within the chest wall. Although esophageal pressure (Pes) measurements are often used to estimate pleural pressures in healthy subjects and patients, they are widely mistrusted and rarely used in critical illness. ⋯ Transpulmonary pressure (airway pressure - Pes) was -2.8 +/- 4.9 cmH(2)O at end exhalation and 8.3 +/- 6.2 cmH(2)O at end inflation, values consistent with effects of mediastinal weight, gravitational gradients in pleural pressure, and airway closure at end exhalation. Lung parenchymal stress measured directly as end-inspiratory transpulmonary pressure was much less than stress inferred from the plateau airway pressures and lung and chest wall compliances. We suggest that Pes can be used to estimate transpulmonary pressures that are consistent with known physiology and can provide meaningful information, otherwise unavailable, in critically ill patients.