Exercise Pathophysiology in Patients With Chronic Mountain Sickness

doi:10.1378/chest.11-2845

Chest

Volume 142, Issue 4, October 2012, Pages 877-884

https://doi.org/10.1378/chest.11-2845 Get rights and content

Background

Chronic mountain sickness (CMS) is characterized by a combination of excessive erythrocytosis, severe hypoxemia, and pulmonary hypertension, all of which affect exercise capacity.

Methods

Thirteen patients with CMS and 15 healthy highlander and 15 newcomer lowlander control subjects were investigated at an altitude of 4,350 m (Cerro de Pasco, Peru). All of them underwent measurements of diffusing capacity of lung for nitric oxide and carbon monoxide at rest, echocardiography for estimation of mean pulmonary arterial pressure and cardiac output at rest and at exercise, and an incremental cycle ergometer cardiopulmonary exercise test.

Results

The patients with CMS, the healthy highlanders, and the newcomer lowlanders reached a similar maximal oxygen uptake at 32 ± 1, 32 ± 2, and 33 ± 2 mL/min/kg, respectively, mean ± SE (P = .8), with ventilatory equivalents for Co₂ vs end-tidal Pco₂, measured at the anaerobic threshold, of 0.9 ± 0.1, 1.2 ± 0.1, and 1.4 ± 0.1 mm Hg, respectively (P < .001); arterial oxygen content of 26 ± 1, 21 ± 2, and 16 ± 1 mL/dL, respectively (P < .001); diffusing capacity for carbon monoxide corrected for alveolar volume of 155% ± 4%, 150% ± 5%, and 120% ± 3% predicted, respectively (P < .001), with diffusing capacity for nitric oxide and carbon monoxide ratios of 4.7 ± 0.1 at sea level decreased to 3.6 ± 0.1, 3.7 ± 0.1, and 3.9 ± 0.1, respectively (P < .05) and a maximal exercise mean pulmonary arterial pressure at 56 ± 4, 42 ± 3, and 31 ± 2 mm Hg, respectively (P < .001).

Conclusions

The aerobic exercise capacity of patients with CMS is preserved in spite of severe pulmonary hypertension and relative hypoventilation, probably by a combination of increased oxygen carrying capacity of the blood and lung diffusion, the latter being predominantly due to an increased capillary blood volume.

Section snippets

Subjects

Thirteen patients with CMS, 15 highlanders, and 15 lowlanders gave informed consent to the study, which had been approved by the institutional review boards of Erasme University Hospital (Brussels, Belgium) and Universidad Cayetano Heredia (Lima, Peru). P2010/164, reference Eudract/CCB: B40620108839. All of the highlanders were born and living at an altitude of 4,350 m (Cerro de Pasco, Peru). The lowlanders were born and living at sea level. The lowlanders were selected to match as closely as

Subjects

Table 1 depicts the clinical characteristics of the three study groups. The patients with CMS were older than those in the healthy highlander and lowlander groups, and in contrast were only men. There were differences in height and weight. However, BMIs were not different between the groups. The patients with CMS had higher Hb and lower Spo₂, but higher Cao₂ compared with the two other groups. The healthy highlanders had similar Spo₂ but higher Hb and Cao₂ compared with lowlanders. Systemic BPs

Discussion

The present results show that aerobic exercise capacity is similarly decreased at high altitude in patients with CMS, in healthy highlanders and in newcomer lowlanders. Exercise pathophysiology in CMS is characterized by a combination of severe pulmonary hypertension, relative hypoventilation, exaggerated hypoxemia, increased Cao₂, and improved lung diffusing capacity. These changes resemble those observed in healthy highlander control subjects, but are more marked, except for lung diffusing

Conclusion

High-altitude residents demonstrate a unique CPET profile characterized by preserved aerobic exercise capacity in spite of pulmonary hypertension and relative hypoventilation, in relation to polycythemia and markedly increased lung diffusing capacity. These characteristics are exaggerated with the development of CMS, excepted for already maximally increased lung diffusing capacity.

Acknowledgments

Author contributions: Mr Groepenhoff and Drs Overbeek and Naeije had full access to all of the data and take complete responsibility for the integrity of the data and the accuracy of the data analysis. All authors approved the final version of the manuscript.

Mr Groepenhoff: contributed to the acquisition, analysis, or interpretation of the data and drafted the manuscript.

Dr Overbeek: contributed to the conception and design of the present study, and to the acquisition, analysis, or

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Global Research Expedition on Altitude-related Chronic Health 2018 Iron Infusion at High Altitude Reduces Hypoxic Pulmonary Vasoconstriction Equally in Both Lowlanders and Healthy Andean Highlanders
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Increasing iron bioavailability attenuates hypoxic pulmonary vasoconstriction in both lowlanders and Sherpas at high altitude. In contrast, the pulmonary vasculature of Andean individuals with chronic mountain sickness (CMS) is resistant to iron administration. Although pulmonary vascular remodeling and hypertension are characteristic features of CMS, the effect of iron administration in healthy Andean individuals, to our knowledge, has not been investigated. If the interplay between iron status and pulmonary vascular tone in healthy Andean individuals remains intact, this could provide valuable clinical insight into the role of iron regulation at high altitude.
Is the pulmonary vasculature in healthy Andean individuals responsive to iron infusion?
In a double-blinded, block-randomized design, 24 healthy high-altitude Andean individuals and 22 partially acclimatized lowlanders at 4,300 m (Cerro de Pasco, Peru) received an IV infusion of either 200 mg of iron (III)-hydroxide sucrose or saline. Markers of iron status were collected at baseline and 4 h after infusion. Echocardiography was performed in participants during room air breathing (partial pressure of inspired oxygen [Pio₂] of approximately 96 mm Hg) and during exaggerated hypoxia (Pio₂ of approximately 73 mm Hg) at baseline and at 2 and 4 h after the infusion.
Iron infusion reduced pulmonary artery systolic pressure (PASP) by approximately 2.5 mm Hg in room air (main effect, P < .001) and by approximately 7 mm Hg during exaggerated hypoxia (main effect, P < .001) in both lowlanders and healthy Andean highlanders. There was no change in PASP after the infusion of saline. Iron metrics were comparable between groups, except for serum ferritin, which was 1.8-fold higher at baseline in the Andean individuals than in the lowlanders (95% CI, 74-121 ng/mL vs 37-70 ng/mL, respectively; P = .003).
The pulmonary vasculature of healthy Andean individuals and lowlanders remains sensitive to iron infusion, and this response seems to differ from the pathologic characteristics of CMS.
Acute, subacute and chronic mountain sickness
2021, Revista Clinica Espanola
Más de 100 millones de personas ascienden cada año a áreas montañosas elevadas en todo el planeta y en altitudes no extremas (< 5.500 m) entre el 10 y el 85% se ven afectados por el denominado mal agudo de montaña, la enfermedad más frecuentemente inducida por una hipoxia hipobárica ligera-moderada. Asimismo, unos 140 millones de seres humanos viven de forma permanente en cotas comprendidas entre 2.500-5.500 m y hasta un 10% de ellos padecen la forma subaguda del mal de montaña (hipertensión pulmonar de la gran altitud) o la forma crónica (enfermedad de Monge), esta última especialmente frecuente en etnias andinas. La presente revisión expone los conceptos generales más relevantes en torno a estas 3 variantes clínicas, las cuales pueden ser incapacitantes, llegar a complicarse y ser potencialmente mortales, siendo esencial realizar una correcta prevención, diagnóstico, terapéutica y manejo de las mismas en un entorno hostil como es la alta montaña.
More than 100 million people ascend to high mountainous areas worldwide every year. At nonextreme altitudes (<5500 m), 10–85% of these individuals are affected by acute mountain sickness, the most common disease induced by mild-moderate hypobaric hypoxia. Approximately 140 million individuals live permanently at heights of 2500–5500 m, and up to 10% of them are affected by the subacute form of mountain sickness (high-altitude pulmonary hypertension) or the chronic form (Monge's disease), the latter of which is especially common in Andean ethnicities. This review presents the most relevant general concepts of these 3 clinical variants, which can be incapacitating and can result in complications and become life-threatening. Proper prevention, diagnosis, treatment and management of these conditions in a hostile environment such as high mountains are therefore essential.
Exercise-Induced Cardiac Fatigue after a 45-Minute Bout of High-Intensity Running Exercise Is Not Altered under Hypoxia
2021, Journal of the American Society of Echocardiography
Acute exercise promotes transient exercise-induced cardiac fatigue, which affects the right ventricle and to a lesser extent the left ventricle. Hypoxic exposure induces an additional increase in right ventricular (RV) afterload. Therefore, exercise in hypoxia may differently affect both ventricles. The aim of this study was to investigate the acute effects of a bout of high-intensity exercise under hypoxia versus normoxia in healthy individuals on right- and left-sided cardiac function and mechanics.
Twenty-one healthy individuals (mean age, 22.2 ± 0.6 years; 14 men) performed 45-min high-intensity running exercise under hypoxia (fraction of inspired oxygen 14.5%) and normoxia (fraction of inspired oxygen 20.9%) in a randomized order. Pre- and post-exercise echocardiography, at rest and during low-to-moderate intensity recumbent exercise (“stress”), was performed to assess RV and left ventricular (LV) cardiac function and mechanics. RV structure, function, and mechanics were assessed using conventional two-dimensional, Doppler, tissue Doppler, speckle-tracking echocardiographic, and novel strain-area loops.
Indices of RV systolic function (RV fractional area change, Tricuspid annular plane systolic excursion, RV s′, and RV free wall strain) and LV function (LV ejection fraction and LV global longitudinal strain) were significantly reduced after high-intensity running exercise (P < .01). These exercise-induced changes were more pronounced when echocardiography was examined during stress compared with baseline. These responses in RV and LV indices were not altered under hypoxia (P > .05).
There was no impact of hypoxia on the magnitude of exercise-induced cardiac fatigue in the right and left ventricles after a 45-min bout of high-intensity exercise. This finding suggests that any potential increase in loading conditions does not automatically exacerbate exercise-induced cardiac fatigue in this setting.
Physiology of the Normal Pulmonary Circulation
2021, Encyclopedia of Respiratory Medicine, Second Edition
The pulmonary circulation is a high-flow/low-pressure circuit. Pulmonary vascular pressure-flow relationships in fully recruited lungs conform to distensible vessel models with a correction for hematocrit. Left atrial pressure is transmitted upstream to pulmonary artery pressure in a less than 1/1 ratio in steady flow conditions, but in a higher than 1/1 ratio in pulsatile flow conditions. The distribution of pulmonary perfusion is mainly determined by gravity, but corrected to some extent by hypoxia-induced vasoconstriction to preserve matching of flow to regional decrease in ventilation. Strenuous exercise and/or hypoxia may be a cause of pulmonary edema or right ventricular failure on high pulmonary vascular pressures.
Noninvasive Pulmonary Hemodynamic Evaluation in Athletes With Exercise-Induced Hypoxemia
2020, Chest
Pulmonary capillary stress failure is potentially involved in exercise-induced hypoxemia (ie, a significant fall in hemoglobin oxygen saturation [Spo₂]) during sea level exercise in endurance-trained athletes. It is unknown whether there are specific properties of pulmonary vascular function in athletes exhibiting oxygen desaturation.
Ten endurance-trained athletes with exercise-induced hypoxemia (EIH), nine endurance-trained athletes with no exercise-induced hypoxemia (NEIH), and 10 untrained control subjects underwent an incremental exercise stress echocardiography coupled with lung diffusion capacity for carbon monoxide (Dlco) and lung diffusion capacity for nitric oxide (Dlno) testing. Functional adaptation of the pulmonary circulation was evaluated with measurements of mean pulmonary arterial pressure (mPAP), pulmonary capillary pressure, pulmonary vascular resistance (PVR), cardiac output (Qc), and pulmonary vascular distensibility (alpha) mathematically determined from the curvilinearity of the multi-point mPAP/Qc relation.
EIH athletes exhibited a lower exercise-induced PVR decrease compared with the untrained and NEIH groups (P < .001). EIH athletes showed higher maximal mPAP compared with NEIH athletes (45.4 ± 0.9 mm Hg vs 41.6 ± 0.9 mm Hg, respectively; P = .003); there was no difference between the NEIH and untrained subjects. Alpha was lower in the EIH group compared with the NEIH group (P < .05). Maximal mPAP, Pcap, and alpha were correlated with the fall of Spo₂ during exercise (P < .01, P < .01, and P < .05). Dlno and Dlco increased with exercise in all groups, with no differences between groups. Dlno/Qc was correlated to the exercise-induced Spo₂ changes (P < .05).
EIH athletes exhibit higher maximal pulmonary vascular pressures, lower vascular distensibility, or exercise-induced changes in PVR compared with NEIH subjects, in keeping with pulmonary capillary stress failure or intrapulmonary shunting hypotheses.
The Right Heart International Network (RIGHT-NET): Rationale, Objectives, Methodology, and Clinical Implications
2018, Heart Failure Clinics
Citation Excerpt :
Subjects will be supervised at least 30 minutes after finishing the test and written informed consent will be obtained for each subject. As recently reviewed,8 exercise-induced PH defined by an abnormally high mPAP alone or in combination with elevated PAWP and CO, measured invasively or noninvasively, has been reported in subjects susceptible to high altitude pulmonary edema, healthy family members of patients with idiopathic PAH, systemic sclerosis, chronic obstructive pulmonary disease or interstitial lung diseases, heart failure with decreased or preserved ejection fraction, mitral valve disease, aortic stenosis, late closure of atrial septal defects, and chronic thromboembolism (see Tables 1–3).19–64 Exercise-induced PH has been typically diagnosed in patients referred for shortness of breath and exercise intolerance without obvious pulmonary or cardiac cause.82

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Funding/Support: This study was supported by the Etna Foundation, Catania, Italy, and by a grant from Pfizer, Inc.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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Chest

Original ResearchPulmonary Vascular DiseaseExercise Pathophysiology in Patients With Chronic Mountain Sickness

Background

Methods

Results

Conclusions

Section snippets

Subjects

Subjects

Discussion

Conclusion

Acknowledgments

Respir Physiol

Nitric Oxide

Chest

J Am Coll Cardiol

Am J Med

Chest

Chest

Respir Physiol

Consensus statement on chronic and subacute high altitude diseases

High Alt Med Biol

The heart and pulmonary circulation at high altitudes: healthy highlanders and chronic mountain sickness

Circulation

Animals in high altitude: resident man

Adaptation to high altitude

N Engl J Med

The Lake Louise acute mountain sickness scoring system

Improvement in lung diffusion by endothelin a receptor blockade at high altitude

J Appl Physiol

Standardisation of the single-breath determination of carbon monoxide uptake in the lung

Eur Respir J

European reference equations for CO and NO lung transfer

Eur Respir J

Exercise stress echocardiography for the study of the pulmonary circulation

Eur Respir J

Analysis of linear and mildly nonlinear relationships using pooled subject data

J Appl Physiol

Distensibility of the normal human lung circulation during exercise

Am J Physiol Lung Cell Mol Physiol

Pulmonary artery pressure limits exercise capacity at high altitude

Eur Respir J

Original Research
Pulmonary Vascular Disease
Exercise Pathophysiology in Patients With Chronic Mountain Sickness