The higher we climb, the lower the oxygen supply to our bodies. Since 2019, a research team from Inserm, Grenoble Alpes University and Grenoble Alpes University Hospital has been investigating the health consequences of oxygen restriction. Their work has taken them to Peru, to Rinconada, the world’s highest city (5,300 m), which has become a veritable open-air laboratory. As part of one of their recent missions, they focused more specifically on the effects of oxygen deprivation on the blood circulation of people living in these territories. The aim was twofold: to help local populations by offering them appropriate medical care, and to better understand the mechanisms at work in hypoxia, a situation where oxygen availability is reduced, as is the case in many cardiovascular and respiratory diseases. Their results, published in The Lancet Regional Health Americas , show how hypoxia alters blood vessel reactivity, which is a prognostic marker of overall health.
Hypoxia is a situation in which the body’s oxygen supply is reduced. It can be encountered in a variety of pathologies, including cardiovascular and respiratory diseases [1] . Studying hypoxia is therefore of crucial importance to better understand the mechanisms at work in these pathologies, and hope one day to improve diagnosis and treatment.
The study of hypoxia has been at the heart of research by the HP2 laboratory team [2] (Inserm/UGA/CHU Grenoble Alpes) for many years. The scientists study hypoxia in the laboratory, and also carry out field studies at high altitude, as part of the Expedition 5300 program (see box below). Higher altitudes are associated with a progressive reduction in oxygen availability. Conducting research in this field means we can study hypoxia in real-life conditions, in people who are constantly confronted with it. Understanding how the human organism can tolerate hypoxia with varying degrees of difficulty could ultimately enable us to individualize care and refine therapeutic management.
In this work, the researchers looked more specifically at the effects of severe hypoxia on the body, and more specifically on the vascular system. Using imaging techniques and blood samples from a group of 94 adults, the scientists measured the reactivity of blood vessels, i.e. their ability to contract or dilate in response to external stimuli. Blood vessel reactivity is commonly regarded as a prognostic marker of overall good health.
More specifically, the researchers measured the reactivity of the vascular system in both large arteries (macrocirculation) and small blood vessels (cutaneous microcirculation) in Peruvian populations living at different altitude levels, including inhabitants of Rinconada, the world’s highest city.
The results of the analyses carried out show a reduced vascular reactivity in people living at high altitude, mainly in those living permanently in a situation of severe hypoxia. Researchers observed that in this group of people [3] , arteries and vessels were permanently dilated, reducing their capacity to dilate further in response to a stimulus. The results obtained point both to a form of adaptation of the body of these inhabitants to a situation of permanent hypoxia (also known as chronic hypoxia), and to the reaching of certain limits of tolerance to severe high-altitude hypoxia, which can lead to health complications (hypertension or heart failure).
The researchers also identified an increase in the inflammatory status of the inhabitants with altitude, and in particular in oxidative stress [4] . The increase in inflammation observed with altitude was associated with a progressive decline in micro- and macrovascular function.
This study enables us to describe for the first time a cascade of mechanisms present in people in situations of chronic hypoxia, from the inflammatory response to its effects on the vascular system," explains Julien Brugniaux, teacher-researcher at Grenoble Alpes University. These results give us a broader understanding of our body’s reactions to oxygen deprivation, and in particular the effects of these situations on ourvascular function", he concludes.
"In addition to providing us with a better understanding of pathologies involving oxygen deficiency, this study, which is part of a wider project we’ve been pursuing since 2019, also enables us to support the health issues of a population subject to harsh living conditions, and sometimes in great precariousness," explains Samuel Vergès, Inserm research director and supervisor of the Expedition 5300 program.
The scientific mission continues for Expedition 5300, which has since returned to the Rinconada to focus more specifically on the health of children living in these chronically hypoxic conditions. The objective ’ to better understand the effects of hypoxia on the growth and development of high-altitude children.
A few words about the Expedition 5300 program
Expedition 5300 was launched in 2019 by researchers from Inserm’s Unit 1300, under the supervision of Inserm Research Director Samuel Vergès. Since then, nearly thirty French and international experts specializing in altitude and hypoxia research have travelled on eight field missions to Peru’s Rinconada.
Their aim is twofold:
- understand the mechanisms of adaptation to altitude hypoxia (comparable to severe chronic hypoxia) to treat patients suffering from oxygen deprivation at La Rinconada ;
- transpose these research results on altitude hypoxia to develop new treatments adapted to pathologies characterized by insufficient oxygenation conditions.
La Rinconada in Peru is the highest town in the world, with over 50,000 inhabitants living at altitudes of between 5,100 and 5,300 m. The town, built around a gold mine, clings to the mountainside beneath the glaciers, imposing extreme living conditions on its inhabitants. Doctors are rare, and many inhabitants have never seen one, even though their living conditions are particularly difficult. No scientific research has ever been carried out in this town, or in any permanent settlement this high up.
[1] Pathologies such as chronic obstructive pulmonary disease, sleep apnea and sickle cell anemia are characterized by the patient’s exposure to conditions of insufficient oxygenation due to respiratory or hematological abnormalities.
[2] Hypoxia and cardiovascular and respiratory pathophysiology laboratory
[3] A total of 38 people lived above 3,800 meters, 17 of them in La Rinconada.
[4] Imbalance between the body’s production of harmful oxidizing agents (notably free radicals) and that of antioxidant agents (such as vitamins E and C). It leads to inflammation and DNA mutations.
