Journal of applied physiology
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The aim of this study was to assess the utility of (3)He MRI to noninvasively probe the effects of positive end-expiratory pressure (PEEP) maneuvers on alveolar recruitment and atelectasis buildup in mechanically ventilated animals. Sprague-Dawley rats (n = 13) were anesthetized, intubated, and ventilated in the supine position ((4)He-to-O(2) ratio: 4:1; tidal volume: 10 ml/kg, 60 breaths/min, and inspiration-to-expiration ratio: 1:2). Recruitment maneuvers consisted of either a stepwise increase of PEEP to 9 cmH(2)O and back to zero end-expiratory pressure or alternating between these two PEEP levels. ⋯ No significant intrasubject differences in ADC were observed between the corresponding PEEP levels in two rats that underwent three repeat maneuvers. Airway pressure tracings were recorded in separate rats undergoing one PEEP maneuver (n = 3) and showed a significant relative difference in peak inspiratory pressure between pre- and poststates. These observations support the hypothesis of redistribution of alveolar gas due to recruitment of collapsed alveoli in presence of atelectasis, which was also supported by the decrease in peak inspiratory pressure after recruitment maneuvers.
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Adenosine triphosphate, acting through purinergic P2X receptors, has been shown to stimulate ventilation and increase carotid body chemoreceptor activity in adult rats. However, its role during postnatal development of the ventilatory response to hypoxia is yet unknown. Using whole body plethysmography, we measured ventilation in normoxia and in moderate hypoxia (12% fraction of inspired O₂, 20 min) before and after intraperitoneal injection of suramin (P2X₂ and P2X₃ receptor antagonist, 40 mg/kg) in 4-, 7-, 12-, and 21-day-old rats. ⋯ Suramin (100 μM) and A-317491 (10 μM) significantly depressed the sinus nerve chemosensory discharge rate (∼80%) in normoxia (Po₂ ∼150 Torr) and hypoxia (Po₂ ∼60 Torr), and this decrease was constant across ages. We conclude that, in newborn rats, P2X purinergic receptors are involved in the regulation of breathing under basal and hypoxic condition, and P2X₃-containing receptors play a major role in carotid body function. However, these effects are not age dependent within the age range studied.
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Diaphragm caspase-8 activation plays a key role in modulating sepsis-induced respiratory muscle dysfunction. It is also known that double-stranded RNA-dependent protein kinase (PKR) is a regulator of caspase-8 activation in neural tissue. We tested the hypothesis that the PKR pathway modulates sepsis-induced diaphragmatic caspase-8 activation. ⋯ Inhibition of PKR with 2-aminopurine prevented endotoxin-induced diaphragm caspase-8 activation (P < 0.01) and diaphragm weakness (P < 0.001). Inhibition of PKR with either 2-aminopurine or transfection with dominant-negative PKR blocked caspase-8 activation in isolated cytokine-treated C₂C₁₂ cells. These data implicate PKR activation as a major factor mediating cytokine-induced skeletal muscle caspase-8 activation and weakness.
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Randomized Controlled Trial Comparative Study
Effect of graded hypoxia on supraspinal contributions to fatigue with unilateral knee-extensor contractions.
Supraspinal fatigue, defined as an exercise-induced decline in force caused by suboptimal output from the motor cortex, accounts for over one-quarter of the force loss after fatiguing contractions of the knee extensors in normoxia. We tested the hypothesis that the relative contribution of supraspinal fatigue would be elevated with increasing severities of acute hypoxia. On separate days, 11 healthy men performed sets of intermittent, isometric, quadriceps contractions at 60% maximal voluntary contraction to task failure in normoxia (inspired O(2) fraction/arterial O(2) saturation = 0.21/98%), mild hypoxia (0.16/93%), moderate hypoxia (0.13/85%), and severe hypoxia (0.10/74%). ⋯ Cortical voluntary activation also declined in all conditions, but the deficit in severe hypoxia exceeded that in normoxia (P < 0.05). The additional central fatigue in severe hypoxia was not due to altered corticospinal excitability, as electromyographic responses to transcranial magnetic stimulation were unchanged. Results indicate that peripheral mechanisms of fatigue contribute relatively more to the reduction in force-generating capacity of the knee extensors following submaximal intermittent isometric contractions in normoxia and mild to moderate hypoxia, whereas supraspinal fatigue plays a greater role in severe hypoxia.
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Comparative Study
Effects of cross-education on the muscle after a period of unilateral limb immobilization using a shoulder sling and swathe.
The purpose of this study was to apply cross-education during 4 wk of unilateral limb immobilization using a shoulder sling and swathe to investigate the effects on muscle strength, muscle size, and muscle activation. Twenty-five right-handed participants were assigned to one of three groups as follows: the Immob + Train group wore a sling and swathe and strength trained (n = 8), the Immob group wore a sling and swathe and did not strength train (n = 8), and the Control group received no treatment (n = 9). Immobilization was applied to the nondominant (left) arm. ⋯ Immobilization in a sling and swathe decreased strength and muscle size but had no effect on maximal voluntary activation or EMG. The cross-education effect on the immobilized limb was greater after elbow extension training. This study suggests that strength training the nonimmobilized limb benefits the immobilized limb for muscle size and strength.