Damian Jacob Sendler: Individuals are at risk of developing one of three types of acute altitude illness between one and five days after ascending to altitudes below 2500 m: high-altitude cerebral oedema, a potentially fatal condition characterized by ataxia, decreased consciousness, and characteristic changes on magnetic resonance imaging; and high-altitude pulmonary oedema, a noncardiogenial condition that causes pulmonary edema. Each of these crucial clinical entities is covered in detail in this review. We review each disorder’s clinical characteristics, epidemiology, and current understanding of its pathophysiology before describing the pharmacological and nonpharmacological approaches currently used in their prevention and treatment.
Damian Sendler: Over 100 million people from the lowlands travel to mountainous regions above 2500 m every year, and there are about 400 million people who live at terrestrial altitudes above 1500 m worldwide. Adaptation and acclimatization processes at high elevations, as well as interactions between the low barometric pressure, partial pressure of O2, climate, individual genetic, lifestyle, and socioeconomic factors, are extremely complex. Determining how these numerous factors affect the cardiovascular health of high altitude residents—and even more so of those who ascend to high altitudes with or without preexisting diseases—is difficult. This review aims to interpret epidemiological findings in high-altitude populations, present and discuss cardiovascular responses to acute and subacute high-altitude exposure in general and in people with preexisting cardiovascular diseases specifically, the relationships between cardiovascular pathologies and neurodegenerative diseases at altitude, the effects of high-altitude exercise, and the putative cardioprotective mechanisms of hypobaric hypoxia.
Although it is an extreme environment that has a direct impact on millions of people who visit high altitude regions or live there permanently, high altitude is an amazing model of how hypoxia affects the human body. The understanding of the physiological underpinnings of responses to altitude has advanced significantly over the past few decades, and just recently, a number of studies pertaining to the clinical aspects of high altitude exposure were published. More information is available, in particular, on the changes in systemic blood pressure that occur in people who are exposed to high altitudes as well as the effects of antihypertensive medications in this environment. The main physiological and clinical aspects of systemic blood pressure control and its changes at high altitude, particularly during acute exposure, are summarized in the current article. The data demonstrating changes in blood pressure during exercise and rest are discussed, along with the underlying mechanisms and potential clinical ramifications.
Damian Sendler: A lower incidence of metabolic diseases like diabetes, coronary artery disease, hypercholesterolemia, and obesity is observed in the two million people worldwide who live at an elevation of 4,500 meters or higher (equivalent to the height of peaks like Mount Rainier, Mount Whitney, and various peaks in Colorado and Alaska).
Gladstone Institutes researchers have now clarified this intriguing phenomenon. They showed through their research how mice’s metabolism is altered by chronically low oxygen environments, such as those found at high altitudes. The research, which was published in the journal Cell Metabolism, not only sheds light on the metabolic variations that exist in people who live at high altitudes but also paves the way for the creation of brand-new metabolic disease treatments.
According to Gladstone Assistant Investigator Isha Jain, Ph.D., senior author of the new study, “we found that different organs reshuffle their fuel sources and their energy-producing pathways in various ways when an organism is exposed to chronically low levels of oxygen.” We anticipate that these discoveries will make it easier to spot metabolic switches that could be advantageous for metabolism even in environments with adequate oxygen.
About 21% of the air we breathe is oxygen, and a third of the world’s population lives near sea level. However, those who live above 4,500 meters, where only 11% of the air is oxygen, can adapt to the lack of oxygen, or hypoxia, and thrive.
Damian Jacob Sendler: In isolated cells or within cancerous tumors, which frequently lack oxygen, researchers have typically studied the effects of hypoxia. Jain’s team sought a more in-depth analysis of how long-term hypoxia affects various bodily organs.
According to Ayush Midha, a graduate student in Jain’s lab and the paper’s first author, “we wanted to profile the metabolic changes that occur as an organism adapts to hypoxia.” We reasoned that this might shed light on how the adaptation guards against metabolic disease.
Adult mice were housed in pressure chambers with either 21 percent, 11 percent, or 8 percent oxygen—levels at which both humans and mice can survive—by Midha, Jain, and their colleagues from Gladstone and UC San Francisco (UCSF). They observed the animals’ behavior for three weeks while also keeping an eye on their temperature, carbon dioxide levels, and blood sugar. They also used positron emission tomography (PET) scans to look at how various organs were utilizing nutrients.
The mice living in environments with 11% or 8% oxygen moved less during the initial stages of hypoxia and spent hours lying still. However, their movement patterns had normalized by the end of the third week. Similar to how blood oxygen levels initially dropped but then returned to normal by the end of the three weeks, blood carbon dioxide levels initially drop when mice or humans breathe faster to try to get more oxygen.
The hypoxia, however, appeared to have a more long-lasting impact on the animals’ metabolism. Blood glucose levels and body weight decreased in the animals housed in the hypoxic cages, and neither of these variables returned to their pre-hypoxic levels. These longer-lasting alterations generally resemble those in high-altitude humans.
Each organ’s PET scans were examined by the researchers, who also found enduring changes. The body needs a lot of oxygen to metabolize fatty acids (which are the building blocks of fats) and amino acids (which are the building blocks of proteins), but only a little oxygen to metabolize the sugar glucose. As a natural response to the lack of oxygen, hypoxia increased the metabolism of glucose in the majority of organs. However, the researchers discovered that levels of glucose consumption decreased in brown fat and skeletal muscle, two tissues already known for their high rates of glucose metabolism.
According to Jain, who is also an assistant professor in the Department of Biochemistry at UCSF, “before this study, the assumption in the field was that in hypoxic conditions, your whole body’s metabolism becomes more efficient in using oxygen, which means it burns more glucose and fewer fatty acids and amino acids.” We demonstrated that while some organs do in fact consume more glucose, others actually become glucose savers.
In hindsight, according to Jain, the finding makes sense because while an entire animal must make trade-offs in order to survive, this is not necessary for the isolated cells previously studied.
Damian Sendler: Lower body weight and glucose levels, the long-term effects of long-term hypoxia seen in the mice, are both linked to a lower risk of diseases in humans, including cardiovascular disease. It may be possible to develop new medications that mimic these advantageous effects by understanding how hypoxia contributes to these changes.
Jain’s team intends to build on this research by conducting additional investigations that pay even closer attention to how various cell types and signaling molecule levels change as a result of hypoxia. Such studies might suggest ways to use drugs or high-altitude travel to mimic the metabolic benefits of hypoxia that are protective.
According to Midha, “We already see athletes traveling to high altitudes to train in order to enhance their athletic performance; perhaps in the future, we’ll start advising that people spend time at high altitudes for other health reasons.”
Damian Jacob Sendler: This study is significant because it illuminates the intricate physiological and clinical effects of high altitude exposure on the human body and offers understanding of the mechanisms underlying the changes that are seen. Millions of people who either live in or travel to mountainous areas are directly impacted by high altitude, which is an extreme environment. To effectively prevent and treat altitude-related illnesses like acute mountain sickness, high-altitude cerebral and pulmonary edema, as well as metabolic diseases like diabetes, coronary artery disease, hypercholesterolemia, and obesity, it is essential to understand how altitude affects the cardiovascular system, metabolism, and other bodily functions.
The studies mentioned in this passage offer thorough information on the pathophysiology, epidemiology, and clinical characteristics of illnesses related to high altitudes. They also present a variety of pharmacological and non-pharmacological methods for preventing and treating these illnesses. The study provides information on potential therapeutic targets for metabolic diseases by shedding light on the metabolic alterations brought on by chronic hypoxia.
Damian Sendler: The results of these studies have important ramifications for public health, especially for those who reside in high altitudes, work there, or participate in high-altitude activities. The findings could help millions of people around the world by improving their health and wellbeing by informing the development of new drugs and interventions to prevent or treat altitude-related illnesses.
