Cardiopulmonary exercise testing before and after intravenous iron in preoperative patients: a prospective clinical study.

Background: Anemia is associated with impaired physical performance and adverse perioperative outcomes. Iron-deficiency anemia is increasingly treated with intravenous iron before elective surgery. We explored the relationship between exercise capacity, anemia, and total hemoglobin mass (tHb-mass) and the response to intravenous iron in anemic patients prior to surgery.

Preparing the patient for surgery to improve outcomes.

The time between contemplation of surgery and the procedure offers a window of opportunity to optimize patients' nutritional, functional and psychological state prior to surgery. Traditionally, preoperative pathways have focused on the underlying disease process and 'fitness for surgery' with physical pre-assessment and risk counselling late in the pathway when little time is available to intervene. With an increasingly elderly and co-morbid surgical population, early physiological assessment and multidisciplinary collaborative decision-making is increasingly important.

Cardiopulmonary exercise testing for risk prediction in major abdominal surgery.

Reduced exercise capacity is associated with increased postoperative morbidity. Cardiopulmonary exercise testing variables can be used to risk stratify patients. This information can be used to help guide the choice of surgical procedure and to decide on the most appropriate postoperative care environment.

Genetic factors associated with exercise performance in atmospheric hypoxia.

Background And Objective: 'Natural selection' has been shown to have enriched the genomes of high-altitude native populations with genetic variants of advantage in this hostile hypoxic environment. In lowlanders who ascend to altitude, genetic factors may also contribute to the substantial interindividual variation in exercise performance noted at altitude. We performed a systematic literature review to identify genetic variants of possible influence on human hypoxic exercise performance, commenting on the strength of any identified associations.

Cardiopulmonary exercise testing, prehabilitation, and Enhanced Recovery After Surgery (ERAS).

Purpose: This review evaluates the current and future role of cardiopulmonary exercise testing (CPET) in the context of Enhanced Recovery After Surgery (ERAS) programs.

Principal Findings: There is substantial literature confirming the relationship between physical fitness and perioperative outcome in general. The few small studies in patients undergoing surgery within an ERAS program describe less fit individuals having a greater incidence of morbidity and mortality.

Changes in muscle proteomics in the course of the Caudwell Research Expedition to Mt. Everest.

This study employed differential proteomic and immunoassay techniques to elucidate the biochemical mechanisms utilized by human muscle (vastus lateralis) in response to high altitude hypoxia exposure. Two groups of subjects, participating in a medical research expedition (A, n = 5, 19 d at 5300 m altitude; B, n = 6, 66 d up to 8848 m) underwent a ≈ 30% drop of muscular creatine kinase and of glycolytic enzymes abundance. Protein abundance of most enzymes of the tricarboxylic acid cycle and oxidative phosphorylation was reduced both in A and, particularly, in B.

Effects of prolonged exposure to hypobaric hypoxia on oxidative stress, inflammation and gluco-insular regulation: the not-so-sweet price for good regulation.

Objectives: The mechanisms by which low oxygen availability are associated with the development of insulin resistance remain obscure. We thus investigated the relationship between such gluco-insular derangements in response to sustained (hypobaric) hypoxemia, and changes in biomarkers of oxidative stress, inflammation and counter-regulatory hormone responses.

Methods: After baseline testing in London (75 m), 24 subjects ascended from Kathmandu (1,300 m) to Everest Base Camp (EBC;5,300 m) over 13 days.

Oral Coenzyme Q10 supplementation does not prevent cardiac alterations during a high altitude trek to everest base cAMP.

Exposure to high altitude is associated with sustained, but reversible, changes in cardiac mass, diastolic function, and high-energy phosphate metabolism. Whilst the underlying mechanisms remain elusive, tissue hypoxia increases generation of reactive oxygen species (ROS), which can stabilize hypoxia-inducible factor (HIF) transcription factors, bringing about transcriptional changes that suppress oxidative phosphorylation and activate autophagy. We therefore investigated whether oral supplementation with an antioxidant, Coenzyme Q10, prevented the cardiac perturbations associated with altitude exposure.

Everest 60 years on: what next?

On 29 May 1953, Sherpa Tenzing Norgay and Edmund Hilary stood on the 8,848 m (29,029 ft) summit of Mount Everest, finally demonstrating that humans could overcome the physical and mental challenges required to conquer the world's highest peak. The 60th anniversary of this event is sadly the first with no member of the original expedition alive, since the death of George Lowe on 20 March 2013 at the age of 89 The successful 1953 expedition followed seven British expeditions to the north side of Everest during the 1920s and 30s. Although unsuccessful, these early expeditions achieved impressive altitudes.

Xtreme Everest 2: unlocking the secrets of the Sherpa phenotype?

Xtreme Everest 2 (XE2) was part of an ongoing programme of field, laboratory and clinical research focused on human responses to hypoxaemia that was conducted by the Caudwell Xtreme Everest Hypoxia Research Consortium. The aim of XE2 was to characterise acclimatisation to environmental hypoxia during a standardised ascent to high altitude in order to identify biomarkers of adaptation and maladaptation. Ultimately, this may lead to novel diagnostic and treatment strategies for the pathophysiological hypoxaemia and cellular hypoxia observed in critically ill patients.

The use of skeletal muscle near infrared spectroscopy and a vascular occlusion test at high altitude.

Microcirculatory function, central to tissue regulation of oxygen flux, may be altered by the chronic hypoxemia experienced at high altitude. We hypothesized that at high altitude, adaptations within skeletal muscle would result in reduced oxygen consumption and reduced microcirculatory responsiveness, detectable by near infrared spectroscopy (NIRS) during a vascular occlusion test (VOT). The VOT comprised 3 min of noninvasive arterial occlusion; thenar eminence tissue oxygenation (Sto2) was measured by NIRS during the VOT at sea level, 4900 m and 5600 m (after 7 and 17 days at altitude, respectively) in 12 healthy volunteers.

Design and conduct of 'Xtreme Alps': a double-blind, randomised controlled study of the effects of dietary nitrate supplementation on acclimatisation to high altitude.

The study of healthy human volunteers ascending to high altitude provides a robust model of the complex physiological interplay that emulates human adaptation to hypoxaemia in clinical conditions. Nitric oxide (NO) metabolism may play an important role in both adaptation to high altitude and response to hypoxaemia during critical illness at sea level. Circulating nitrate and nitrite concentrations can be augmented by dietary supplementation and this is associated with improved exercise performance and mitochondrial efficiency.

The Young Everest Study: preliminary report of changes in sleep and cerebral blood flow velocity during slow ascent to altitude in unacclimatised children.

Background: Cerebral blood flow velocity (CBFV) and sleep physiology in healthy children exposed to hypoxia and hypocarbia are under-researched.

Aim: To investigate associations between sleep variables, daytime end-tidal carbon dioxide (EtCO2) and CBFV in children during high-altitude ascent.

Methods: Vital signs, overnight cardiorespiratory sleep studies and transcranial Doppler were undertaken in nine children (aged 6-13 years) at low altitude (130 m), and then at moderate (1300 m) and high (3500 m) altitude during a 5-day ascent.

The role of nitrogen oxides in human adaptation to hypoxia.

Lowland residents adapt to the reduced oxygen availability at high altitude through a process known as acclimatisation, but the molecular changes underpinning these functional alterations are not well understood. Using an integrated biochemical/whole-body physiology approach we here show that plasma biomarkers of NO production (nitrite, nitrate) and activity (cGMP) are elevated on acclimatisation to high altitude while S-nitrosothiols are initially consumed, suggesting multiple nitrogen oxides contribute to improve hypoxia tolerance by enhancing NO availability. Unexpectedly, oxygen cost of exercise and mechanical efficiency remain unchanged with ascent while microvascular blood flow correlates inversely with nitrite.

Acclimatization of skeletal muscle mitochondria to high-altitude hypoxia during an ascent of Everest.

Ascent to high altitude is associated with a fall in the partial pressure of inspired oxygen (hypobaric hypoxia). For oxidative tissues such as skeletal muscle, resultant cellular hypoxia necessitates acclimatization to optimize energy metabolism and restrict oxidative stress, with changes in gene and protein expression that alter mitochondrial function. It is known that lowlanders returning from high altitude have decreased muscle mitochondrial densities, yet the underlying transcriptional mechanisms and time course are poorly understood.

Cerebral artery dilatation maintains cerebral oxygenation at extreme altitude and in acute hypoxia--an ultrasound and MRI study.

Transcranial Doppler is a widely used noninvasive technique for assessing cerebral artery blood flow. All previous high altitude studies assessing cerebral blood flow (CBF) in the field that have used Doppler to measure arterial blood velocity have assumed vessel diameter to not alter. Here, we report two studies that demonstrate this is not the case.

Stroke at high altitude diagnosed in the field using portable ultrasound.

A tool that can differentiate ischemic stroke from other neurological conditions (eg, hemorrhagic stroke, high-altitude cerebral edema) in the field could enable more rapid thrombolysis when appropriate. The resources (eg, an MRI or CT scanner) to investigate stroke at high altitude may be limited, and hence a portable tool would be of benefit. Such a tool may also be of benefit in emergency departments when CT scanning is not available.

Cardiac response to hypobaric hypoxia: persistent changes in cardiac mass, function, and energy metabolism after a trek to Mt. Everest Base Camp.

We postulated that changes in cardiac high-energy phosphate metabolism may underlie the myocardial dysfunction caused by hypobaric hypoxia. Healthy volunteers (n=14) were studied immediately before, and within 4 d of return from, a 17-d trek to Mt. Everest Base Camp (5300 m).

Design and conduct of Caudwell Xtreme Everest: an observational cohort study of variation in human adaptation to progressive environmental hypoxia.

Background: The physiological responses to hypoxaemia and cellular hypoxia are poorly understood, and inter-individual differences in performance at altitude and outcome in critical illness remain unexplained. We propose a model for exploring adaptation to hypoxia in the critically ill: the study of healthy humans, progressively exposed to environmental hypobaric hypoxia (EHH). The aim of this study was to describe the spectrum of adaptive responses in humans exposed to graded EHH and identify factors (physiological and genetic) associated with inter-individual variation in these responses.

Caudwell xtreme Everest expedition.

The Caudwell Xtreme Everest (CXE) expedition involved the detailed study of 222 subjects ascending to 5300 m or higher during the first half of 2007. Following baseline measurements at sea level, 198 trekker-subjects trekked to Everest Base Camp (EBC) following an identical ascent profile. An additional group of 24 investigator-subjects followed a similar ascent to EBC and remained there for the duration of the expedition, with a subgroup of 14 collecting data higher on Everest.

Changes in sublingual microcirculatory flow index and vessel density on ascent to altitude.

We hypothesized that ascent to altitude would result in reduced sublingual microcirculatory flow index (MFI) and increased vessel density. Twenty-four subjects were studied using sidestream dark-field imaging, as they ascended to 5300 m; one cohort remained at this altitude (n = 10), while another ascended higher (maximum 8848 m; n = 14). The MFI, vessel density and grid crossings (GX; an alternative density measure) were calculated.

Changes in skeletal muscle oxygenation during exercise measured by near-infrared spectroscopy on ascent to altitude.

Introduction: We sought to quantify changes in skeletal muscle oxygenation during exercise using near-infrared spectroscopy (NIRS) in healthy volunteers ascending to high altitude.

Methods: Using NIRS, skeletal muscle tissue oxygen saturation (StO2) was measured in the vastus lateralis of 24 subjects. Measurements were performed at sea level (SL; 75 m), at 3,500 m, on arrival at 5,300 m (5,300 m-a; days 15 to 17) and at 5,300 m again (5,300 m-b; days 69 to 71).

Variation in human performance in the hypoxic mountain environment.

Ascent to altitude is associated with a fall in barometric pressure, and with it a decline in the partial pressure of atmospheric (and thus alveolar) oxygen. As a result, a variety of adaptive physiological processes are engaged to mitigate the fall in tissue convective oxygen delivery which might otherwise occur. The magnitude and nature of such changes is also modified with time, a process known as acclimatization.