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Correspondence |

Increased Oxidative Stress at AltitudeIncreased Oxidative Stress at Altitude FREE TO VIEW

J. Ashley Jefferson, MD; Elizabeth Escudero, MD; Richard J. Johnson, MD; Erik R. Swenson, MD; Abdias Hurtado, MD
Author and Funding Information

From the Division of Nephrology (Dr Jefferson), University of Washington; Carlos Monge Cassinelli Nephrology Center (Drs Escudero and Hurtado), University of Cayetano Heredia; Division of Nephrology (Dr Johnson), University of Colorado; and Division of Pulmonary and Critical Care Medicine, Department of Medicine (Dr Swenson), VA Puget Sound Health Care System, University of Washington.

Correspondence to: J. Ashley Jefferson, MD, University of Washington, Division of Nephrology, 1959 NE Pacific St, Box 356174, Seattle, WA 98195; e-mail: jashleyj@u.washington.edu


Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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


Chest. 2014;145(2):423. doi:10.1378/chest.13-2062
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To the Editor:

We read with interest the study in CHEST (February 2013) by Bailey et al1 in which they describe increased oxidative-nitrosative stress in people who live in a high altitude. In their article, they stated that “there are no studies, to our knowledge, that have examined this response during lifelong exposure to high altitude in healthy, well-adapted and maladapted highlanders.”1 Hypoxia has been associated with oxidative stress in in vitro experiments,2 in animal models exposed to hypobaric hypoxia,3 in humans acutely exposed to high altitude,4 and in simulated altitude.5

We would like to highlight our prior study. We investigated oxidative stress in both acute exposure to high altitude (48 h in volunteers at sea level; n = 28) and chronic exposure to high altitude in the Andes (healthy residents at high altitude [n = 25] and residents at high altitude [n = 27] with abnormal adaptation to high-altitude living, a condition known as chronic mountain sickness).6 Assessment of oxidative stress was performed by measuring oxidation products in plasma (thiobarbituric acid reactive substances) and urine (F2-isoprostanes [8-isoprostaglandin F2a]). As an assessment of antioxidant status, we measured total plasma glutathione.

Our study confirmed that both acute (48 h) and chronic exposure to high altitude are associated with increased levels of lipid peroxidation, and these levels correlate with increased plasma levels of total glutathione. Patients chronically living at high altitude have elevated levels of plasma total glutathione and lipid peroxidation products, and the subgroup with chronic mountain sickness, or Monge disease, has significantly greater levels of lipid peroxidation compared to control subjects at sea level and control subjects at high altitude. Indeed, in our study, the subjects with the highest degree of oxidative stress also had elevated blood cobalt levels, likely related to contamination from the local mines.7 Currently, we are conducting a clinical trial to see if we can both chelate the cobalt and reduce the oxidative stress with N-acetylcysteine.

References

Bailey DM, Rimoldi SF, Rexhaj E, et al. Oxidative-nitrosative stress and systemic vascular function in highlanders with and without exaggerated hypoxemia. Chest. 2013;143(2):444-451. [CrossRef] [PubMed]
 
Duranteau J, Chandel NS, Kulisz A, Shao Z, Schumacker PT. Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes. J Biol Chem. 1998;273(19):11619-11624. [CrossRef] [PubMed]
 
Sarada SK, Dipti P, Anju B, et al. Antioxidant effect of beta-carotene on hypoxia induced oxidative stress in male albino rats. J Ethnopharmacol. 2002;79(2):149-153. [CrossRef] [PubMed]
 
Richalet JP, Hornych A, Rathat C, Aumont J, Larmignat P, Rémy P. Plasma prostaglandins, leukotrienes and thromboxane in acute high altitude hypoxia. Respir Physiol. 1991;85(2):205-215. [CrossRef] [PubMed]
 
Joanny P, Steinberg J, Robach P, et al. Operation Everest III (Comex’97): the effect of simulated sever hypobaric hypoxia on lipid peroxidation and antioxidant defence systems in human blood at rest and after maximal exercise. Resuscitation. 2001;49(3):307-314. [CrossRef] [PubMed]
 
Jefferson JA, Simoni J, Escudero E, et al. Increased oxidative stress following acute and chronic high altitude exposure. High Alt Med Biol. 2004;5(1):61-69. [CrossRef] [PubMed]
 
Jefferson JA, Escudero E, Hurtado ME, et al. Excessive erythrocytosis, chronic mountain sickness, and serum cobalt levels. Lancet. 2002;359(9304):407-408. [CrossRef] [PubMed]
 

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References

Bailey DM, Rimoldi SF, Rexhaj E, et al. Oxidative-nitrosative stress and systemic vascular function in highlanders with and without exaggerated hypoxemia. Chest. 2013;143(2):444-451. [CrossRef] [PubMed]
 
Duranteau J, Chandel NS, Kulisz A, Shao Z, Schumacker PT. Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes. J Biol Chem. 1998;273(19):11619-11624. [CrossRef] [PubMed]
 
Sarada SK, Dipti P, Anju B, et al. Antioxidant effect of beta-carotene on hypoxia induced oxidative stress in male albino rats. J Ethnopharmacol. 2002;79(2):149-153. [CrossRef] [PubMed]
 
Richalet JP, Hornych A, Rathat C, Aumont J, Larmignat P, Rémy P. Plasma prostaglandins, leukotrienes and thromboxane in acute high altitude hypoxia. Respir Physiol. 1991;85(2):205-215. [CrossRef] [PubMed]
 
Joanny P, Steinberg J, Robach P, et al. Operation Everest III (Comex’97): the effect of simulated sever hypobaric hypoxia on lipid peroxidation and antioxidant defence systems in human blood at rest and after maximal exercise. Resuscitation. 2001;49(3):307-314. [CrossRef] [PubMed]
 
Jefferson JA, Simoni J, Escudero E, et al. Increased oxidative stress following acute and chronic high altitude exposure. High Alt Med Biol. 2004;5(1):61-69. [CrossRef] [PubMed]
 
Jefferson JA, Escudero E, Hurtado ME, et al. Excessive erythrocytosis, chronic mountain sickness, and serum cobalt levels. Lancet. 2002;359(9304):407-408. [CrossRef] [PubMed]
 
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