Commentary on Point-Counterpoint

The purpose of this review is to describe changes in blood volume and erythropoietic activity occurring under different types of intermittent exposure to hypoxia. These hypoxic episodes can vary from a few seconds or minutes to hours, days, or even weeks. Short hypoxic episodes like sleep apnea only lead to a small increase in hemoglobin concentration, which is mainly due to a hormonal-mediated decrease in plasma volume. In most of these cases the cumulative time spent under hypoxia does not exceed the critical threshold of about 90 min. Endurance athletes and mountaineers who voluntarily expose themselves to hypoxia for some hours or during the night while spending the day at normoxia ("sleep high-train low" concept) do improve their physical performance. Despite raising erythropoietic activity, indicated by elevated plasma concentrations of EPO and the transferrin receptor, the postulated increase in red cell volume has not satisfactorily been proved. Frequent changes between low and high altitudes, which are usual in some South American and Asian countries, provoke similar adaptations in red cell mass as occur in high altitude residents. However, the plasma volume decreases at altitude and increases again when staying at sea level. Even after more than 20 yr of regular moving between low and high altitude, the total blood volume, hemoglobin concentration and hematocrit, as well as the plasma EPO concentration, noticeably oscillate during every hypoxic-normoxic cycle. We assume these changes to be an optimal rapid adaptation of the oxygen transport system to the prevailing hypoxic or normoxic environment. However, possible risks for the organism cannot be excluded.

Physiological and performance effects of live high train low altitude training for elite endurance athletes: A narrative review

There is debate as to which environmental intervention produces the most benefit for team sport athletes, particularly comparing heat and altitude. This quasi-experimental study aimed to compare blood volume (BV) responses with heat and altitude training camps in Australian footballers. The BV of 7 professional Australian footballers (91.8 [10.5]kg, 191.8 [10.1]cm) was measured throughout 3 consecutive spring/summer preseasons. During each preseason, players participated in altitude (year 1 and year 2) and heat (year 3) environmental training camps. Year 1 and year 2 altitude camps were in November/December in the United States, whereas the year 3 heat camp was in February/March in Australia after a full exposure to summer heat. BV, red cell volume, and plasma volume (PV) were measured at least 3 times during each preseason. Red cell volume increased substantially following altitude in both year 1 (d = 0.67) and year 2 (d = 1.03), before returning to baseline 4 weeks postaltitude. Immediately following altitude, concurrent decreases in PV were observed during year 1 (d = -0.40) and year 2 (d = -0.98). With spring/summer training in year 3, BV and PV were substantially higher in January than temporally matched postaltitude measurements during year 1 (BV: d = -0.93, PV: d = -1.07) and year 2 (BV: d = -1.99, PV: d = -2.25), with year 3 total BV, red cell volume, and PV not changing further despite the 6-day heat intervention. We found greater BV after training throughout spring/summer conditions, compared with interrupting spring/summer exposure to train at altitude in the cold, with no additional benefits observed from a heat camp following spring/summer training.

reports of a relationship between altitude and circulating levels of leptin suggest a possible role of hypoxia in leptin regulation. However, studies on the changes in plasma leptin levels at altitude are controversial, with some showing an increase and others suggesting no change or a fall in these

Ramchandani, Rashi, Ioana Tereza Florica, Zier Zhou, Aziz Alemi, and Adrian Baranchuk. Review of athletic guidelines for high-altitude training and acclimatization. High Alt Med Biol. 00:000-000, 2024. Introduction: Exposure to high altitude results in hypobaric hypoxia with physiological acclimatization changes that are thought to influence athletic performance. This review summarizes existing literature regarding implications of high-altitude training and altitude-related guidelines from major governing bodies of sports. Methods: A nonsystematic review was performed using PubMed and OVID Medline to identify articles regarding altitude training and guidelines from international governing bodies of various sports. Sports inherently involving training or competing at high altitude were excluded. Results: Important physiological compensatory mechanisms to high-altitude environments include elevations in blood pressure, heart rate, red blood cell mass, tidal volume, and respiratory rate. These responses can have varying effects on athletic performance. Governing sport bodies have limited and differing regulations for training and competition at high altitudes with recommended acclimatization periods ranging from 3 days to 3 weeks. Discussion: Physiological changes in response to high terrestrial altitude exposure can have substantial impacts on athletic performance. Major sport governing bodies have limited regulations and recommendations regarding altitude training and competition. Existing guidelines are variable and lack substantial evidence to support recommendations. Additional studies are needed to clarify the implications of high-altitude exposure on athletic ability to optimize training and competition.

This review focuses on the effects of altitude exposure from 1 to several days or weeks as occurs in tourists, trekkers, and mountaineers who visit high altitude and normally reside near sea level. We briefly review the acute physiological adjustments and early acclimatization that occur in the cardiovascular system and the lungs of healthy individuals. These ensure life-sustaining oxygen delivery to the tissues despite a reduction in the partial pressure of inspired oxygen between 20% and 60% at 2500 and 8000 m, respectively. One of the acute adjustments, hypoxic pulmonary vasoconstriction (HPV), may be disadvantageous in those with a vigorous response and lead to 2 potentially lethal illnesses, high-altitude pulmonary edema (HAPE) and subacute mountain sickness (SAMS), which we present in more detail. Finally, on the basis of knowledge about the acute physiological adjustments and acclimatization and, when available, a review of the literature, we discuss the high-altitude tolerance of patients with coronary artery disease, congestive heart failure, arrhythmias, systemic hypertension, and pulmonary hypertension. ### Circulation The major effects of acute hypoxia on the heart and lung are shown in Figure 1. Hypoxia directly affects the vascular tone of the pulmonary and systemic resistance vessels and increases ventilation and sympathetic activity via stimulation of the peripheral chemoreceptors.1 Interactions occur between the direct effects of hypoxia on blood vessels and the chemoreceptor-mediated responses in the systemic and pulmonary circulation. Figure 1. Effects of hypoxia on systemic and pulmonary circulation. Unraveling the underlying mechanisms of the hypoxic vasodilatation of systemic arterioles is an active area of research. Several mechanisms appear to regulate local oxygen delivery according to the needs of the tissues2,3; for instance, the release of ATP from red blood cells and the generation of NO by various ways appear to regulate local oxygen delivery according to the needs …

Altitude training at 2690m does not increase total Haemoglobin mass or sea level V̇O 2max in world champion track cyclists

Intermittent hypoxia as a means to improve aerobic capacity in type 2 diabetes

The correlation between relative haemoglobin mass (Hb mass, g x kg[-1]) and relative maximal oxygen consumption (VO2max, ml x kg(-1) x min[-1]) in 62 trained athletes (33 male runners, 12 male rowers and 17 female rowers) with national and/ or international competitive experience was examined. The correlation between Hb mass and VO2max was highest for the female rowers (n=17, r=0.92, p<0.0001), lower for the male rowers (n = 12, r=0.79, p < 0.005) and lowest for the male runners (n=33, r=0.48, p = 0.005). These results suggest that, within an athletic sample, Hb mass may be used to estimate potential aerobic power. In a second series of experiments, Hb mass was measured before and after three different training programs in sub-sets of the subjects used in the earlier study. Hb mass did not change following 12 weeks of intense rowing training, 4 weeks of heat training (32 degrees C), or 4 weeks of medium-altitude training (1740 m). The corresponding increases in VO2max were 7.8%, no change and 2.1 %, respectively. These results suggest that heat or altitude training does not increase Hb mass in trained athletes. Previous studies that demonstrate increases in total red cell volume following altitude acclimatization used subjects with only modest aerobic power, whereas the present study used trained subjects. It is concluded that trained athletes with erythrocythemic hypervolemia have limited capability to increase further either total red cell volume or Hb mass.

The importance of oxygen transport and consumption in the body for endurance performance is the reason why altitude training as preparation for competitions at sea level has become popular. In hypoxia maximal O2 uptake decreases. Thus for equal work load training at altitude is harder and stimulates adaptation processes more than sea level training. A specific altitude training effect, however, can only be proven if a relative equal load (in % of VO2max) is more effective than during sea level training. In only three of 10 investigations with this design has a significant improvement of either maximal performance, VO2max or endurance been found, in two there was a nonsignificant tendency. When training in hypoxia combined with living in normoxia was investigated two of four groups improved. Living in hypoxia with training in normoxia is probably more effective but only preliminary publications are available. Summarizing, a small specific altitude effect on performance capacity seems to exist, which may be counteracted by negative influences like reduced stimulation of muscular metabolism. A series of single physiological changes at altitude might have positive or negative implications on training success: training of respiratory muscles, increase of hypoxic ventilatory stimulation, reduced heart training by vegetative "braking", increase of red cell and plasma volume (the latter after descent), right shift of the oxygen dissociation curve, increase of oxidative muscle enzymes (only after hypoxia training), shift from fat and muscle glycogen to blood glucose combustion, reduced lactic acid and ammonia production, increase in buffer capacity.

In order to evaluate the haemodynamic response to exercise in Standardbred trotters with red cell hypervolaemia (RCHV), 12 trotters with RCHV were compared with 9 normovolaemic (NV) trotters. Haemodynamic data were recorded during exercise at 4 different speeds on a treadmill. Oxygen uptake was determined with an open bias flow system. Pulmonary artery pressure (PAP), systemic artery pressure (SAP), heart rate, packed cell volume (PCV) and plasma lactate and haemoglobin ([Hb]) concentrations were measured. Arteriovenous O2 content difference, cardiac output, stroke volume, pulmonary vascular resistance (PVR) and total systemic resistance (TSR) were calculated. Oxygen uptake, arteriovenous O2 content difference, heart rate, cardiac output, stroke volume, TSR and lactate did not differ between groups. The RCHV horses had significantly higher both mean diastolic and systolic PAP compared to NV horses and this difference increased with higher workload. Further, a higher SAP, PVR, PCV and [Hb] were found in RCHV horses during the course of exercise. Eleven of the RCHV horses, but none of the NV, showed exercise-induced pulmonary haemorrhage on endoscopic examination. The increase in red cell volume, resulting in a high PCV and high total blood volume, is suggested to be an important contributor to both the increased blood pressures in pulmonary and systemic circulation during exercise and to the development of exercise-induced pulmonary haemorrhage in RCHV horses.

Fifteen severely anaemic patients receiving CAPD were treated with subcutaneous recombinant human erythropoietin (Epo). Ten subjects had a good response with the haemoglobin concentration increasing from less than 8 g/dl to greater than 10 g/dl within 16 weeks. Four patients had a poor response, which was due to infection in two, myelofibrosis in one and unknown cause in another. Epo was ineffective in the remaining individual, probably due to the presence of occult metastatic carcinoma. Iron supplementation in the form of intravenous iron dextran was given to 12 patients when transferrin saturation decreased below 20%. There was a significant increase in red cell volume (P less than 0.005), with a decrease in plasma volume (P less than 0.005). Red cell iron turnover increased (P less than 0.05) but there was no change in red cell lifespan or deformability. Biochemical parameters remained unaltered, as did peritoneal function. Exercise duration improved (P less than 0.001), as did maximal oxygen consumption (P less than 0.01). Four patients required an increased dose of hypotensive drugs. Epo is a safe effective therapy for the anaemia of CAPD subjects.

In chronic heart failure, dilutional anemia and hypervolemia may occur due to plasma volume expansion, the latter sometimes exacerbated by an increase in red cell volume. Diagnosis and a therapeutic strategy require determination of vascular volumes.

Cardiovascular diseases, including ischemic heart disease, are the leading cause of premature death and disability worldwide. While traditional risk factors such as smoking, obesity, and diabetes have been thoroughly investigated, non-traditional risk factors like high-altitude exposure remain underexplored. This study aims to examine the incidence and mortality rates of ischemic heart disease over the past decade in Ecuador, a country with a diverse altitude profile spanning from 0 to 4,300 meters. We conducted a geographic distribution analysis of ischemic heart disease in Ecuador, utilizing hospital discharge and mortality data from the National Institute of Census and Statistics for the years 2011-2021. Altitude exposure was categorized according to two distinct classifications: the traditional division into low (< 2,500 m) and high (> 2,500 m) altitudes, as well as the classification proposed by the International Society of Mountain Medicine, which delineates low (< 1,500 m), moderate (1,500-2,500 m), high (2,500-3,500 m), and very high (3,500-5,800 m) altitudes. From 2011-2021, we analyzed 49,765 IHD-related hospital admissions and 62,620 deaths. Men had an age-adjusted incidence rate of 55.08/100,000 and a mortality rate of 47.2/100,000, compared to 20.77/100,000 and 34.8/100,000 in women. Incidence and mortality surged in 2020 by 83% in men and 75% in women. Altitudinal stratification revealed higher IHD rates at lower altitudes (<2500 m), averaging 61.65 and 121.8 per 100,000 for incidence and mortality, which declined to 25.9 and 38.5 at elevations >2500 m. Men had more pronounced rates across altitudes, exhibiting 138.7% and 150.0% higher incidence at low and high altitudes respectively, and mortality rates increased by 48.3% at low altitudes and 23.2% at high altitudes relative to women. Ecuador bears a significant burden of ischemic heart disease (IHD), with men being more affected than women in terms of incidence. However, women have a higher percentage of mortality post-hospital admission. Regarding elevation, our analysis, using two different altitude cutoff points, reveals higher mortality rates in low-altitude regions compared to high-altitude areas, suggesting a potential protective effect of high elevation on IHD risk. Nevertheless, a definitive dose-response relationship between high altitude and reduced IHD risk could not be conclusively established.

Saunders, Christopher Gore, David B. Pyne, and Philo U. training for endurance at altitude. In 2023, 10: 135-148 High Alt. Med. Biol. Moderate training at high altitudes (*2000 to 3000m) has gained popularity as a way to enhance competitive performances at ocean level and at mountain since the first Olympic Games in 1968, when it became evident how altitude affected endurance events. Reduced stroke volume, decreased plasma volume, increased breathing, raised heart rate, and a *15% to 20% drop in maximal aerobic power (V˙o2max) are some of the physiological reactions that can affect endurance athletes' ability to perform at altitude when modest altitude is abruptly applied to them. The rise in the red blood cell volume and, consequently, V˙o2max is one significant acclimation reaction that takes place over just a few weeks. In order to get these answers, sufficient iron reserves and elevations &gt;*2000m for &gt;3 weeks are needed. However, the world's top endurance athletes (*2000 to 3000m) from Ethiopia had only slightly higher hemoglobin concentrations, making it difficult to determine if having a higher number of red blood cells is more important for better sea level performance. The significant decrease in V˙o2max observed in athletes at intermediate altitude suggests that in order to prevent a decline in race-specific fitness, athlete training must be incorporate sufficient long-duration (*5 to 7min), long-intensity struggle with hard recoveries. At the top level, V˙o2max is not the only factor that affects an athlete's achievement, the "smallest acceptable improvement" that can enhance race results is as little as 0.5%. Therefore, while trying to understand the possible benefits and processes associated with altitude training, in comparison with classic methods of statistical analysis, current statistical approaches that utilize the concept of the lowest meaningful improvement are likely more appropriate.