Globally, about 400 million people reside at terrestrial altitudes above 1500 m, and more than 100 million lowlanders visit mountainous areas above 2500 m annually. The interactions between the low ...barometric pressure and partial pressure of O
, climate, individual genetic, lifestyle and socio-economic factors, as well as adaptation and acclimatization processes at high elevations are extremely complex. It is challenging to decipher the effects of these myriad factors on the cardiovascular health in high altitude residents, and even more so in those ascending to high altitudes with or without preexisting diseases. This review aims to interpret epidemiological observations in high-altitude populations; present and discuss cardiovascular responses to acute and subacute high-altitude exposure in general and more specifically in people with preexisting cardiovascular diseases; the relations between cardiovascular pathologies and neurodegenerative diseases at altitude; the effects of high-altitude exercise; and the putative cardioprotective mechanisms of hypobaric hypoxia.
Purpose
The aim of this study was to establish a model to estimate the level of arterial oxygen saturation (SpO
2
) and help determine the appropriate hypoxic dose in humans exercising in acute ...hypoxia.
Methods
SpO
2
values were collected in seven untrained (UTS) and seven endurance-trained male subjects (ETS) who performed six cycle incremental and maximal tests at sea level and at simulated altitudes of 1000, 1500, 2500, 3500 and 4500 m. Oxygen uptake was continuously measured and maximal oxygen uptake (
V
˙
O
2
max
) was determined in each subject and at each altitude. Intensity was expressed as percentage of
V
˙
O
2
max
.
Results
There were strong non-linear relationships between altitude and SpO
2
at low, moderate and high intensity both in ETS and UTS (
r
= 0.97,
p
< 0.001). SpO
2
was significantly correlated to exercise intensity at sea level and at all simulated altitudes in ETS but only from 2500 m in UTS. There were inverse correlations between SpO
2
and sea-level
V
˙
O
2
max
at all altitudes, which were stronger from 2500 m and with the increase in exercise intensity. The three-variable model we established predicts (
p
< 0.001) the SpO
2
level of individuals exercising in acute hypoxia based on their sea-level
V
˙
O
2
max
, the intensity of exercise and the altitude level.
Conclusion
The model demonstrates that the drop of SpO
2
during exercise in acute hypoxia is larger with the increase in both sea-level
V
˙
O
2
max
and exercise intensity. The model also highlights that the pivotal altitude from which the fall in SpO
2
is exacerbated is between 2000 and 2500 m, depending on both sea-level
V
˙
O
2
max
and exercise intensity.
Exposure to high altitude induces a decrease in oxygen pressure and saturation in the arterial blood, which is aggravated by exercise. Heart rate (HR) at maximal exercise decreases when altitude ...increases in prolonged exposure to hypoxia. We developed a simple model of myocardial oxygenation in order to demonstrate that the observed blunting of maximal HR at high altitude is necessary for the maintenance of a normal myocardial oxygenation. Using data from the available scientific literature, we estimated the myocardial venous oxygen pressure and saturation at maximal exercise in two conditions: (1) with actual values of maximal HR (decreasing with altitude); (2) with sea‐level values of maximal heart rate, whatever the altitude (no change in HR). We demonstrated that, in the absence of autoregulation of maximal HR, myocardial tissue oxygenation would be incompatible with life above 6200 m–7600 m, depending on the hypothesis concerning a possible increase in coronary reserve (increase in coronary blood flow at exercise). The decrease in maximal HR at high altitude could be explained by several biological mechanisms involving the autonomic nervous system and its receptors on myocytes. These experimental and clinical observations support the hypothesis that there exists an integrated system at the cellular level, which protects the myocardium from a hazardous disequilibrium between O2 supply and O2 consumption at high altitude.
Maximal heart rate (HR) is known to be lower at high altitude than at sea level, but the underlying mechanisms are still to be fully explained. From field data extracted from subjects exercising at maximal intensity above 4000 m, our model shows that an unchanged HR at high altitude would imply myocardial oxygenation inadequate for functioning and survival. Hence, local mechanisms, relying on the regulation of the autonomic nervous system, would play a key role in preventing myocardium from a potentially harmful high metabolic demand. This is a remarkable example of autoregulation of a vital organ facing extreme constraints.
Tolerance to high altitude in women might be influenced by hormonal status since female hormones modulate ventilation.
Our objectives were (i) to explore in 1060 women, the influence of the phase of ...menstrual cycle, oral contraception, and menopause with or without hormonal treatment, on hypoxic ventilatory response at exercise (HVRe) and hypoxic cardiac response at exercise (HCRe) measured during a routine hypoxia exercise test, before an exposure to high altitude; (ii) to determine in 260 women exposed to high altitude, the influence of menopause and oral contraceptive and other drug use, on the prevalence of severe acute mountain sickness (sAMS). Four groups were defined: premenopausal with or without oral contraception and postmenopausal with or without hormonal treatment.
In premenopausal women without contraception, HVRe was higher in the early luteal/midluteal phase than in the early follicular phase (0.89 ± 0.37 vs. 0.75 ± 0.27 mL/min · kg,
= 0.03). HVRe was similar in postmenopausal versus premenopausal women. HCRe was lower in postmenopausal women (
< 0.001), due to aging. HVRe decreased from second to fourth decade of age and increased from fourth to eighth decade, while HCRe consistently decreased with aging. Oral contraception or hormonal treatment had no effect on responses to hypoxia. The prevalence of sAMS was similar in all groups. Severe high-altitude illness score was higher and HVRe lower in women with sAMS.
(i) physiological responses to hypoxic exercise depend on the ovarian cycle phase and menopause status, (ii) oral contraception and hormonal treatment have no influence on the tolerance to high altitude, and (iii) independent of hormonal status, aging modulates physiological responses to hypoxia.
An increasing number of persons, exposed to high altitude for leisure, sport, or work, may suffer from severe high-altitude illness.
To assess, in a large cohort of subjects, the association between ...physiological parameters and the risk of altitude illness and their discrimination ability in a risk prediction model.
A total of 1,326 persons went through a hypoxic exercise test before a sojourn above 4,000 m. They were then monitored up at high altitude and classified as suffering from severe high-altitude illness (SHAI) or not. Analysis was stratified according to acetazolamide use.
Severe acute mountain sickness occurred in 314 (23.7%), high-altitude pulmonary edema in 22 (1.7%), and high-altitude cerebral edema in 13 (0.98%) patients. Among nonacetazolamide users (n = 917), main factors independently associated with SHAI were previous history of SHAI (adjusted odds ratios aOR, 12.82; 95% confidence interval CI, 6.95-23.66; P < 0.001), ascent greater than 400 m/day (aOR, 5.89; 95% CI, 3.78-9.16; P < 0.001), history of migraine (aOR, 2.28; 95% CI, 1.28-4.07; P = 0.005), ventilatory response to hypoxia at exercise less than 0.78 L/minute/kg (aOR, 6.68; 95% CI, 3.83-11.63; P < 0.001), and desaturation at exercise in hypoxia equal to or greater than 22% (aOR, 2.50; 95% CI, 1.52-4.11; P < 0.001). The last two parameters improved substantially the discrimination ability of the multivariate prediction model (C-statistic rose from 0.81 to 0.88; P < 0.001). Preventive use of acetazolamide reduced the relative risk of SHAI by 44%.
In a large population of altitude visitors, chemosensitivity parameters (high desaturation and low ventilatory response to hypoxia at exercise) were independent predictors of severe high-altitude illness. They improved the discrimination ability of a risk prediction model.
The adrenergic system is part of a full array of mechanisms allowing the human body to adapt to the hypoxic environment. Triggered by the stimulation of peripheral chemoreceptors, the adrenergic ...centers in the medulla are activated in acute hypoxia and augment the adrenergic drive to the organs, especially to the heart, leading to tachycardia. With prolonged exposure to altitude hypoxia, the adrenergic drive persists, as witnessed by elevated blood concentrations of catecholamines and nerve activity in adrenergic fibers. In response to this persistent stimulation, the pathways leading to the activation of adenylate cyclase are modified. A downregulation of β-adrenergic and adenosinergic receptors is observed, while muscarinic receptors are upregulated. The expression and activity of Gi and Gs proteins are modified, leading to a decreased response of adenylate cyclase activity to adrenergic stimulation. The clinical consequences of these cellular and molecular changes are of importance, especially for exercise performance and protection of heart function. The decrease in maximal exercise heart rate in prolonged hypoxia is fully accounted for the observed changes in adrenergic and muscarinic pathways. The decreased heart rate response to isoproterenol infusion is another marker of the desensitization of adrenergic pathways. These changes can be considered as mechanisms protecting the heart from a too high oxygen consumption in conditions where the oxygen availability is severely reduced. Similarly, intermittent exposure to hypoxia has been shown to protect the heart from an ischemic insult with similar mechanisms involving G proteins and downregulation of β receptors. Other pathways with G proteins are concerned in adaptation to hypoxia, such as lactate release by the muscles and renal handling of calcium. Altogether, the activation of the adrenergic system is useful for the acute physiological response to hypoxia. With prolonged exposure to hypoxia, the autonomous nervous system adapts to protect vital organs, especially the heart, against a too high energetic state, via a purely local autoregulation mechanism necessary for the preservation of overall homeostasis.
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