A neurogenic basis for acute altitude illness

Krasney, J. A.

doi:10.1249/00005768-199402000-00010

Cited by 99 publications

(54 citation statements)

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“…A shorter duration of the exposure to hypoxia, a less profound degree of O 2 desaturation, and/or a different ventilatory pattern at low altitude and high altitude (10,25,31) could account for the inability to elicit in AMS subjects during short-term hypoxia the same response observed at high altitude. Conversely, it could also be possible that subjects with AMS have preserved sympathetic cardiac modulation at rest and in response to hypoxia and that the LF RR NU abnormalities observed at high altitude are secondary to established mountain sickness (7,15).…”

Section: Cardiovascular Variability At Low Altitudementioning

confidence: 99%

Autonomic cardiovascular regulation in subjects with acute mountain sickness

Lanfranchi¹,

Colombo²,

Cremona³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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The aims of this study were 1) to evaluate whether subjects suffering from acute mountain sickness (AMS) during exposure to high altitude have signs of autonomic dysfunction and 2) to verify whether autonomic variables at low altitude may identify subjects who are prone to develop AMS. Forty-one mountaineers were studied at 4,559-m altitude. AMS was diagnosed using the Lake Louise score, and autonomic cardiovascular function was explored using spectral analysis of R-R interval and blood pressure (BP) variability on 10-min resting recordings. Seventeen subjects (41%) had AMS. Subjects with AMS were older than those without AMS (P Ͻ 0.01). At high altitude, the lowfrequency (LF) component of systolic BP variability (LFSBP) was higher (P ϭ 0.02) and the LF component of R-R variability in normalized units (LFRRNU) was lower (P ϭ 0.001) in subjects with AMS. After 3 mo, 21 subjects (43% with AMS) repeated the evaluation at low altitude at rest and in response to a hypoxic gas mixture. LFRRNU was similar in the two groups at baseline and during hypoxia at low altitude but increased only in subjects without AMS at high altitude (P Ͻ 0.001) and did not change between low and high altitude in subjects with AMS. Conversely, LFSBP increased significantly during short-term hypoxia only in subjects with AMS, who also had higher resting BP (P Ͻ 0.05) than those without AMS. Autonomic cardiovascular dysfunction accompanies AMS. Marked LFSBP response to short-term hypoxia identifies AMS-prone subjects, supporting the potential role of an exaggerated individual chemoreflex vasoconstrictive response to hypoxia in the genesis of AMS.hypoxia; autonomic nervous system; heart rate; blood pressure ACUTE MOUNTAIN SICKNESS (AMS) is a complex syndrome characterized by headache, gastrointestinal symptoms, weakness, insomnia, and certain neurological signs, including ataxia and changes in mental status (1). It may occur in subjects ascending to Ͼ2,500 m and is reported in 53% of those at Ͼ4,000-m altitude (6,22).AMS is generally harmless and transient but may occasionally progress to the more serious life-threatening cerebral and pulmonary forms of mountain sickness, i.e., high-altitude cerebral and pulmonary edema (1, 6).The exact mechanism causing AMS is unknown, although the prevailing hypothesis points to a process within the central nervous system (1), possibly an altered adaptation to the neurohumoral and hemodynamic adjustments during hypoxia (8). A marked increase in peripheral sympathetic activity is a common feature of mountain sickness (4, 11) and has also been suggested to contribute to the genesis of high-altitude pulmonary edema (4). Whether autonomic hyperactivation may play a role in the genesis of AMS is not known.The autonomic nervous system plays a role in the modulation of the oscillatory behavior of the cardiovascular system (23, 32a). Spectral analysis of variability in the R-R interval is a recognized tool that allows quantification of the oscillatory components, which in short-term recordings appear mainly organized...

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Section: Cardiovascular Variability At Low Altitudementioning

confidence: 99%

Autonomic cardiovascular regulation in subjects with acute mountain sickness

Lanfranchi¹,

Colombo²,

Cremona³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…endothelial cells; cytoarchitecture; blood-brain barrier; immunofluorescence WHEREAS RESEARCH INVOLVING hypoxic stress has traditionally focused on identifying and treating risk factors associated with ischemic stroke (17,18,43), hypoxia as a result of high-altitude exposure has also been associated with impairment in neurological function (26,37). Early intervention after ischemic stroke has been shown to reduce tissue damage associated with increased cerebrovascular permeability (7,39).…”

mentioning

confidence: 99%

Cerebral microvascular changes in permeability and tight junctions induced by hypoxia-reoxygenation

Mark

Davis

2002

American Journal of Physiology-Heart and Circulatory Physiology

339

272

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Mark, Karen S., and Thomas P. Davis. Cerebral microvascular changes in permeability and tight junctions induced by hypoxia-reoxygenation. Am J Physiol Heart Circ Physiol 282: H1485-H1494, 2002; 10.1152/ajpheart.00645.2001.-Cerebral microvessel endothelial cells that form the bloodbrain barrier (BBB) have tight junctions (TJ) that are critical for maintaining brain homeostasis and low permeability. Both integral (claudin-1 and occludin) and membrane-associated zonula occluden-1 and -2 (ZO-1 and ZO-2) proteins combine to form these TJ complexes that are anchored to the cytoskeletal architecture (actin). Disruptions of the BBB have been attributed to hypoxic conditions that occur with ischemic stroke, pathologies of decreased perfusion, and high-altitude exposure. The effects of hypoxia and posthypoxic reoxygenation in cerebral microvasculature and corresponding cellular mechanisms involved in disrupting the BBB remain unclear. This study examined hypoxia and posthypoxic reoxygenation effects on paracellular permeability and changes in actin and TJ proteins using primary bovine brain microvessel endothelial cells (BBMEC). Hypoxia induced a 2.6-fold increase in [ 14 C]sucrose, a marker of paracellular permeability. This effect was significantly reduced (ϳ58%) with posthypoxic reoxygenation. After hypoxia and posthypoxic reoxygenation, actin expression was increased (1.4-and 2.3-fold, respectively). Whereas little change was observed in TJ protein expression immediately after hypoxia, a twofold increase in expression was seen with posthypoxic reoxygenation. Furthermore, immunofluorescence studies showed alterations in occludin, ZO-1, and ZO-2 protein localization during hypoxia and posthypoxic reoxygenation that correlate with the observed changes in BBMEC permeability. The results of this study show hypoxia-induced changes in paracellular permeability may be due to perturbation of TJ complexes and that posthypoxic reoxygenation reverses these effects. endothelial cells; cytoarchitecture; blood-brain barrier; immunofluorescence WHEREAS RESEARCH INVOLVING hypoxic stress has traditionally focused on identifying and treating risk factors associated with ischemic stroke (17,18,43), hypoxia as a result of high-altitude exposure has also been associated with impairment in neurological function (26,37). Early intervention after ischemic stroke has been shown to reduce tissue damage associated with increased cerebrovascular permeability (7, 39). Recently, research has expanded into examining cellular effects of cerebral ischemia-reperfusion. Ischemic stroke is a reduction or cessation of blood flow to the brain, which deprives the cerebral tissue of important nutrients and oxygen as well as removal of metabolic waste products. Whereas this decrease in oxygen supply to the brain (i.e., hypoxia) has been shown to increase cerebrovascular permeability (1,19), there are also reports (42, 66) of increased permeability in peripheral and cerebral endothelial cells during posthypoxic reperfusion (i.e., reoxygenation). Little is know...

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“…Although there is evidence that endothelial dysfunction may contribute to exaggerated altitude-induced pulmonary vasoconstriction, 1,8 observations in animals and humans are consistent with the hypothesis that sympathetic activation may also play a role. 7,9,10 In dogs, blockade of the stellate ganglion prevents pulmonary edema and lung injury evoked by intravenous infusion of oleic acid. 10 In subjects suffering from HAPE, infusion of the ␣-adrenergic blocking agent phentolamine evokes significantly larger decreases in pulmonary artery pressure than infusion of nonspecific vasodilator drugs.…”

mentioning

confidence: 99%

Augmented Sympathetic Activation During Short-Term Hypoxia and High-Altitude Exposure in Subjects Susceptible to High-Altitude Pulmonary Edema

et al. 1999

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Background-Pulmonary hypertension is a hallmark of high-altitude pulmonary edema and may contribute to its pathogenesis. Cardiovascular adjustments to hypoxia are mediated, at least in part, by the sympathetic nervous system, and sympathetic activation promotes pulmonary vasoconstriction and alveolar fluid flooding in experimental animals. Methods and Results-We measured sympathetic nerve activity (using intraneural microelectrodes) in 8 mountaineers susceptible to high-altitude pulmonary edema and 7 mountaineers resistant to this condition during short-term hypoxic breathing at low altitude and at rest at a high-altitude laboratory (4559 m). We also measured systolic pulmonary artery pressure to examine the relationship between sympathetic activation and pulmonary vasoconstriction. In subjects prone to pulmonary edema, short-term hypoxic breathing at low altitude evoked comparable hypoxemia but a 2-to 3-times-larger increase in the rate of the sympathetic nerve discharge than in subjects resistant to edema (PϽ0.001). At high altitude, in subjects prone to edema, the increase in the meanϮSE sympathetic firing rate was Ͼ2 times larger than in those resistant to edema (36Ϯ7 versus 15Ϯ4 bursts per minute, PϽ0.001) and preceded the development of lung edema. We observed a direct relationship between sympathetic nerve activity and pulmonary artery pressure measured at low and high altitude in the 2 groups (rϭ0.83, PϽ0.0001). Conclusions-With the use of direct measurements of postganglionic sympathetic nerve discharge, these data provide the first evidence for an exaggerated sympathetic activation in subjects prone to high-altitude pulmonary edema both during short-term hypoxic breathing at low altitude and during actual high-altitude exposure. Sympathetic overactivation may contribute to high-altitude pulmonary edema. (Circulation. 1999;99:1713-1718.)

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A neurogenic basis for acute altitude illness

Cited by 99 publications

References 0 publications

Autonomic cardiovascular regulation in subjects with acute mountain sickness

Autonomic cardiovascular regulation in subjects with acute mountain sickness

Cerebral microvascular changes in permeability and tight junctions induced by hypoxia-reoxygenation

Augmented Sympathetic Activation During Short-Term Hypoxia and High-Altitude Exposure in Subjects Susceptible to High-Altitude Pulmonary Edema

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