Robert C Roach

University of Colorado | UCD · Altitude Research Center

Introduction: Acute altitude exposure lowers arterial oxygen content (CaO2) and cardiac output ( c) at peak exercise, whilst O2 extraction from blood to working muscles remains similar. Acclimatization normalizes CaO2 but not peak c nor peak oxygen consumption ( O2p). To what extent acclimatization impacts muscle O2 extraction remains unresolved....

Introduction: A lack of knowledge among laypersons about the hazards of high-altitude exposure contributes to morbidity and mortality from acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE) among high-altitude travelers. There are guidelines regarding the recognition, prevention, and treatme...

Due to lack of nuclei and de novo protein synthesis, post-translational modification (PTM) is imperative for erythrocytes to regulate oxygen (O2) delivery and combat tissue hypoxia. Here, we report that erythrocyte transglutminase-2 (eTG2)-mediated PTM is essential to trigger O2 delivery by promoting bisphosphoglycerate mutase proteostasis and the...

New findings: What is the central question to this study? Is there a relationship between a patent foramen ovale and the development of acute mountain sickness and an exaggerated increase in pulmonary pressure in response to 7-10 h of normobaric hypoxia? What is the main finding and its importance? Patent foramen ovale presence did not increase su...

New findings: What is the central question of this study? Does the combination of methazolamide and theophylline reduce symptoms of acute mountain sickness (AMS) and improve aerobic performance in acute hypobaric hypoxia? What is the main finding and its importance? The oral combination of methazolamide (100 BID) and theophylline (300 BID) improve...

IntroductionBaroreflex sensitivity (BRS) is essential to ensure rapid adjustment to variations in blood pressure (BP). Spontaneous baroreflex function can be assessed using continuous recordings of blood pressure. The goal of this study was to compare four methods for BRS quantification [the sequence, Bernardi’s (BER), frequency and transfer functi...

Acclimatization to hypoxia allows humans to climb to over 8000 m without supplemental oxygen (Everest is 8850 m), while exposure to the same altitude without acclimatization results in death in minutes. How does this happen? Much is known about the physiology, but discoveries are still occurring. And the whole spectrum of molecular responses drivin...

Introduction: Baroreflex sensitivity (BRS) is essential to ensure rapid adjustment to variations in blood pressure (BP). Little is known concerning the adaptive responses of BRS during acclimatization to high altitude at rest and during exercise. Methods: Twenty-one healthy sea-level residents were tested near sea level (SL, 130 m), the 1st (ALT1)...

Metabolic responses to hypoxia play important roles in cell survival strategies and disease pathogenesis in humans. However, the homeostatic adjustments that balance changes in energy supply and demand to maintain organismal function under chronic low oxygen conditions remain incompletely understood, making it difficult to distinguish adaptive from...

Roach, Robert C., Peter H. Hackett, Oswald Oelz, Peter Bärtsch, Andrew M. Luks, Martin J. MacInnis, J. Kenneth Baillie, and The Lake Louise AMS Score Consensus Committee. The 2018 Lake Louise Acute Mountain Sickness Score. High Alt Med Biol 00:000-000, 2018.- The Lake Louise Acute Mountain Sickness (AMS) scoring system has been a useful research to...

Blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA) occurs in healthy humans at rest and during exercise when breathing hypoxic gas mixtures at sea level and may be a source of right-to-left shunt. However, at high altitude QIPAVA is reduced compared to sea level as detected using transthoracic saline contrast echocardiography (TTS...

Introduction: Suicide rates are greater at high altitudes, and multiple mechanisms have been suggested for this relationship, including hypoxia, differences in population density, characteristics of suicide victims, and firearms ownership and access. To better understand these potential mechanisms, studies evaluating the associations between high...

Hypoxanthine catabolism in vivo is potentially dangerous as it fuels production of urate and, most importantly, hydrogen peroxide. However, it is unclear whether accumulation of intracellular and supernatant hypoxanthine in stored RBC units is clinically relevant for transfused recipients. Leukoreduced RBCs from G6PD-normal or -deficient human volu...

State of the art proteomics technologies have recently helped to elucidate the unanticipated complexity of red blood cell metabolism. One recent example is citrate metabolism, which is catalyzed by cytosolic isoforms of Krebs cycle enzymes that are present and active in mature erythrocytes and was determined using quantitative metabolic flux analys...

Erythrocytes are vital to human adaptation under hypoxic conditions because of their abundance in number and irreplaceable function of delivering oxygen (O2). However, although multiple large-scale altitude studies investigating the overall coordination of the human body for hypoxia adaptation have been conducted, detailed research with a focus on...

Assessing the physiological responses to exercise at high altitude in real time or using cloud-based data storage has important implications for remote monitoring of human health and well-being in challenging environments. Purpose: To determine the feasibility of using real-time monitoring to assess the cardiovascular responses to a simulated climb...

INTRODUCTION: Civilian and military personnel often endure heavy exercise loads at high altitude. To improve performance at altitude, it is important to understand what factors predict human performance at high altitude. PURPOSE: To assess whether a physical fitness test at sea-level can be used to predict exercise performance at high altitude. MET...

Faster acclimatization to high altitude upon re-ascent is seen in humans; however, the molecular basis for this enhanced adaptive response is unknown. We report that in healthy lowlanders, plasma adenosine levels are rapidly induced by initial ascent to high altitude and achieved even higher levels upon re-ascent, a feature that is positively assoc...

Supplementary Figures

The purpose of this study was to test the efficacy of four medications to offset the expected decrement in performance during a simulated rapid deployment at altitude. In this double blind, placebo controlled, matched cohort design study, subjects (N = 102) participated in a three-day trip to high altitude (10,000-13,000 feet) that simulated a mili...

Introduction: Acute Mountain Sickness (AMS) poses a significant threat to anyone who travels too high, too quickly to high altitude. New, safe and effective approaches to prevention and treatment of AMS have been lacking. Based on previous animal work (Quercetin, Nifedipine+Methazolamide and Metformin) and positive results in hypoxia for humans wit...

Methods: We utilized a previously published cohort of 28 adolescents from Leadville, Colorado, that underwent right heart catheterization at 10,150 ft (3094 m) in 1962, with many demonstrating PH as defined by resting mean pulmonary arterial pressure ≥25 mmHg. We located participants of the original study and had living subjects complete demograph...

Erythropoiesis is an extremely dynamic process finely regulated by cytokines, hormones, and growth factors at transcriptional and translational levels. Stress-induced erythropoiesis is defined as a stimulated basal erythropoiesis with expansion of the erythroid progenitor pool, associated with reticulocytosis and splenomegaly. Stress erythropoiesis...

Improved and faster acclimatization to high altitude upon re-ascent is seen in humans. However, molecular basis for initial acclimatization and retention upon re-ascent to high altitude remains largely unknown. Here we report that plasma adenosine levels are induced by high altitude and retained at higher levels upon re-ascent in health lowlanders...

Erythropoiesis is an extremely dynamic process finely regulated by cytokines, hormones, and growth factors at transcriptional and translational levels. Stress-induced erythropoiesis is defined as a stimulated basal erythropoiesis with expansion of the erythroid progenitor pool, associated with reticulocytosis and splenomegaly. Stress erythropoiesis...

Methods: Using a cross-sectional survey design, a convenience sample of 667 hikers participated in a written survey after descent from Mount Gray/Torreys (4349 m). Headaches were characterized as migraine, high altitude headache (HAH), and/or acute mountain sickness (AMS) using International Headache Society Lake Louise AMS scoring criteria. A uni...

Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hypoxia through the so-called oxygen-dependent metabolic regulation, which involves the competitive binding of deoxyhemoglobin and glycolytic enzymes to the N-terminal cytosolic domain of band 3. This mechanism promotes the accumulation of 2,3-DPG, stabili...

Background: High altitude is a challenging condition caused by insufficient oxygen supply. Inability to adjust to hypoxia may lead to pulmonary edema, stroke, cardiovascular dysfunction, and even death. Thus, understanding the molecular basis of adaptation to high altitude may reveal novel therapeutics to counteract the detrimental consequences of...

Investigating mitochondrial responses to hypoxia may reveal plasticity of cellular bioenergetics relevant to the study of environmental adaptation and chronic disease. The present study evaluated the bioenergetic phenotype of vastus lateralis muscle biopsies from 15 subjects at sea level and following 16 d at 5200 m by high resolution respirometry...

Sphingosine-1-phosphate (S1P) is a bioactive signalling lipid highly enriched in mature erythrocytes, with unknown functions pertaining to erythrocyte physiology. Here by employing nonbiased high-throughput metabolomic profiling, we show that erythrocyte S1P levels rapidly increase in 21 healthy lowland volunteers at 5,260 m altitude on day 1 and c...

Supplementary Figures 1-6

Raw Values

Previous studies reported enhanced cerebrovascular CO2 reactivity upon ascent to high altitude using linear models. However, there is evidence that this response may be sigmoidal in nature. Moreover, it was speculated that these changes at high altitude are mediated by alterations in acid-base buffering. Accordingly, we reanalyzed previously publis...

The latest in a series of books from the International Hypoxia Symposia, this volume spans reviews on key topics in hypoxia, and abstracts from poster and oral presentations. The biannual International Hypoxia Symposia are dedicated to hosting the best basic scientific and clinical minds to focus on the integrative and translational biology of hypo...

The pathophysiology of acute mountain sickness and high-altitude cerebral edema, the cerebral forms of high-altitude illness, remain uncertain and controversial. Persistently elevated or pathological fluctuations in intracranial pressure are thought to cause symptoms similar to those reported by individuals suffering cerebral forms of high-altitude...

The occurrence and implications of changes in cerebral autoregulation (CA) at high altitude are controversial and confounded by differences in methods used to assess CA. To compare two of the most common methods of dynamic CA assessment, we studied 11 young, healthy sea-level residents (six females and five males; 20.5 ± 2.3 years old) as they asce...

Little is known about early genomic responses in human adaptation to high‐altitude hypoxia. At 5260 m (PB=406 Torr) we studied transcriptomic and epigenomic responses of 21 young, healthy men and women during 16 days, and again on return after 7 days in normoxia. Physiological responses showed marked improvement in performance at day 16 compared to...

A patent foramen ovale (PFO), present in ~40% of the general population, is a potential source of right-to-left shunt that can impair pulmonary gas exchange efficiency [i.e., increase the alveolar-to-arterial PO2 difference (A-aDO2)]. Prior studies investigating human acclimatization to high-altitude with A-aDO2 as a key parameter have not investig...

how humans and other organisms sense and respond to hypoxia is a rapidly growing research field, with more than 19,000 MedLine citations on hypoxia in the last 2 years alone. Reflecting the growing and widespread interest in hypoxia, this is the fourth Highlighted Topic in the Journal of Applied

To function effectively in O2 uptake, delivery and release, erythrocytes rely on sophisticated regulation of hemoglobin (Hb)-O2 affinity by allosteric modulators, especially 2,3-bisphophosphoglycerate (2,3-BPG). Earlier studies had shown that elevated erythrocyte 2,3-BPG level is correlated to increased availability of oxygen to tissues in high alt...

New findings: What is the central question of this study? Whether cerebral autoregulation (CA) is impaired at high altitude and associated with acute mountain sickness remains controversial. We sought to compare two of the most common methods to assess dynamic CA in subjects who ascended to 3424 m and acclimatized. What is the main finding and its...

It is classically thought that increases in hemoglobin mass (Hbmass) take several weeks to develop upon ascent to high altitude and are lost gradually following descent. However, the early time course of these erythropoietic adaptations has not been thoroughly investigated and data are lacking at elevations greater than 5000 m, where the hypoxic st...

Humans experiencing hypoxic conditions exhibit multiple signs of cognitive impairment, and high altitude expeditions may be undermined by abrupt degradation in mental performance. Therefore, the development of psychometric tools to quickly and accurately assess cognitive impairment is of great importance in aiding medical decision-making in the fie...

We asked whether acclimatisation to chronic hypoxia (CH) attenuates the level of supraspinal fatigue that is observed after locomotor exercise in acute hypoxia (AH). Seven recreationally-active participants performed identical bouts of constant-load cycling (131±39W, 10.1±1.4min) on three occasions: 1) in normoxia (N, PI O2 , 147.1mmHg); 2) in AH (...

Adequate oxygen supply to the brain is critical to maintain brain function. Hypoxia presents a unique challenge in maintaining sufficient cerebral oxygen delivery (DO2). We assessed by ultrasound cerebral blood flow (CBF: internal carotid, vertebral arteries and middle cerebral artery velocity [MCAv]) and arterial blood pressure (index of cerebral...

The early time course of changes in hemoglobin mass (Hbmass) and red cell volume (RCV) following ascent to and descent from altitudes greater than 5000m has not been previously determined in humans. We examined Hbmass and blood volume (BV) compartments in healthy men (n = 12) and women (n = 9) at sea level (SL) and 5260m following 1, 7, and 16 days...

A PFO is a source of intracardiac shunt causing impaired pulmonary gas exchange efficiency, defined by an increased alveolar‐to‐arterial PO 2 difference (AaDO 2 ). Prior studies investigating human acclimatization to high altitude (HA) have not investigated differences between subjects with a patent foramen ovale (PFO+) and those without (PFO−), ye...

To function effectively in O 2 uptake, and unload, erythrocytes rely on sophisticated regulation of hemoglobin (Hb)‐O 2 affinity by allosteric modulators. One of the best known allosteric modulators is 2,3‐bisphophosphoglycerate (2,3‐BPG). Earlier studies demonstrated that erythrocyte 2,3‐BPG levels are elevated at a high altitude. However, what tr...

An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics pro...

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