The Journal of physiology
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The Journal of physiology · Mar 2014
Randomized Controlled Trial Comparative StudyConduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation.
Research detailing the normal vascular adaptions to high altitude is minimal and often confounded by pathology (e.g., chronic mountain sickness) and methodological issues. We examined vascular function and structure in: (1) healthy lowlanders during acute hypoxia and prolonged (∼2 weeks) exposure to high altitude, and (2) high-altitude natives at 5050 m (highlanders). In 12 healthy lowlanders (aged 32 ± 7 years) and 12 highlanders (Sherpa; 33 ± 14 years) we assessed brachial endothelium-dependent flow-mediated dilatation (FMD), endothelium-independent dilatation (via glyceryl trinitrate; GTN), common carotid intima-media thickness (CIMT) and diameter (ultrasound), and arterial stiffness via pulse wave velocity (PWV; applanation tonometry). ⋯ In a follow-up, placebo-controlled experiment (n = 11 healthy lowlanders) conducted in a normobaric hypoxic chamber (inspired O2 fraction (F IO 2) = 0.11; 6 h), a sustained reduction in FMD was evident within 1 h of hypoxic exposure when compared to normoxic baseline (5.7 ± 1.6 vs. 8.0 ±1.3%; P < 0.01); this decline in FMD was largely reversed following α1-adrenoreceptor blockade. In conclusion, high-altitude exposure in lowlanders caused persistent impairment in vascular function, which was mediated partially via oxidative stress and sympathoexcitation. Although a lifetime of high-altitude exposure neither intensifies nor attenuates the impairments seen with short-term exposure, chronic high-altitude exposure appears to be associated with arterial remodelling.
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The Journal of physiology · Oct 2012
Randomized Controlled Trial Controlled Clinical TrialLong-term facilitation of ventilation following acute continuous hypoxia in awake humans during sustained hypercapnia.
In awake humans, long-term facilitation of ventilation (vLTF) following acute intermittent hypoxia (AIH) is only expressed if CO2 is maintained above normocapnic levels. vLTF has not been reported following acute continuous hypoxia (ACH) and it is not known whether this might be unmasked by elevated CO2. Twelve healthy participants completed three trials. In all trials end-tidal pressure of CO2 was elevated 4-5 mmHg above normocapnic levels. ⋯ In awake humans with elevated CO2, ACH evokes a sustained increase in ventilation that is comparable to that evoked by AIH. However, a gradual positive drift in ventilation in response to elevated CO2 accounts for approximately half of this apparent vLTF. Additionally, our data support the view that the CB is not directly involved in maintaining vLTF.
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The Journal of physiology · Mar 2012
Randomized Controlled Trial Clinical TrialAcetazolamide improves loop gain but not the other physiological traits causing obstructive sleep apnoea.
There is some evidence to suggest that acetazolamide may improve obstructive sleep apnoea (OSA). However, how acetazolamide affects the key traits causing OSA remains uncertain. We aimed to investigate the effect of acetazolamide on the traits contributing to OSA and its severity. ⋯ There was a modest correlation between the percentage reduction in LG and the percentage reduction in AHI (r =0.660, P =0.05). Our findings suggest that acetazolamide can improve OSA, probably due to reductions in the sensitivity of the ventilatory control system. Identification of patients who may benefit from reductions in LG alone or in combination with other therapies to alter the remaining traits may facilitate pharmacological resolution of OSA in the future.
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The Journal of physiology · Mar 2012
Randomized Controlled Trial Clinical TrialEffects of acetazolamide on cerebrovascular function and breathing stability at 5050 m.
One of the many actions of the carbonic anhydrase inhibitor, acetazolamide (ACZ), is to accelerate acclimatisation and reduce periodic breathing during sleep. The mechanism(s) by which ACZ may improve breathing stability, especially at high altitude, remain unclear. We tested the hypothesis that acute I. ⋯ V. ACZ elevates cerebrovascular reactivity and improves breathing stability at altitude, independent of changes in peripheral or central chemoreflex sensitivities. We speculate that Pa,CO₂-mediated elevations in cerebral perfusion and an enhanced cerebrovascular reactivity may partly account for the improved breathing stability following ACZ at high altitude.
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The Journal of physiology · Jun 2011
Randomized Controlled TrialSpecific modulation of corticospinal and spinal excitabilities during maximal voluntary isometric, shortening and lengthening contractions in synergist muscles.
This study was designed to investigate the cortical and spinal mechanisms involved in the modulations of neural activation during lengthening compared with isometric and shortening maximal voluntary contractions (MVCs). Two muscles susceptible to different neural adjustments at the spinal level, the soleus (SOL) and medial gastrocnemius (MG), were compared. Twelve healthy males participated in at least two experimental sessions designed to assess corticospinal and spinal excitabilities. ⋯ Similar observations were obtained regardless of the initial length of the MG muscle. Collectively, the current results indicate that the relative contribution of both cortical and spinal mechanisms to the modulation of neural activation differs during lengthening MVCs and between two synergist muscles. The comparison of SOL and MG responses further suggests that the specific modulation of the corticospinal excitability during lengthening MVCs depends mainly on pre- and postsynaptic inhibitory mechanisms acting at the spinal level.