Antoni Ricart

Erythropoietin acute reaction and haematological adaptations to short, intermittent hypobaric hypoxia.

Abstract This study aimed to determine whether brief hypoxic stimuli in a hypobaric chamber are able to elicit erythropoietin (EPO) secretion, and to effectively stimulate erythropoiesis in the short term. In two different experiments, a set of haematological, biochemical, haemorheological, aerobic performance, and medical tests were performed in two groups of healthy subjects. In the first experiment, the mean plasma concentration of EPO ([EPO]) increased from 8.7 to 13.5 mU · ml−1 (55.2%; P < 0.01) after 90 min of acute exposure at 540 hPa, and continued to rise until a peak was attained 3 h after the termination of hypoxia. In the second experiment, in which subjects were exposed to a simulated altitude of up to 5500 m (504 hPa) for 90 min, three times a week for 3 weeks, all haematological indicators of red cell mass increased significantly, reaching the highest mean values at the end of the programme or during the subsequent 2 weeks, including packed cell volume (from 42.5 to 45.1%; P < 0.01), red blood cell count (from 4.55 × 106 to 4.86 × 106 · l−1; P < 0.01), reticulocytes (from 0.5 to 1.4%; P < 0.01), and haemoglobin concentration (from 14.3 to 16.2 g · dl−1; P < 0.01), without an increase in blood viscosity. Arterial blood oxygen saturation during hypoxia was improved (from 60% to 78%; P < 0.05). Our most relevant finding is the ability to effectively stimulate erythropoiesis through brief intermittent hypoxic stimuli (90 min), in a short period of time (3 weeks), leading to a lower arterial blood desaturation in hypoxia. The proposed mechanism for these haematological and functional adaptations is the repeated triggering effect of EPO production caused by the intermittent hypoxic stimuli.

Intermittent hypobaric hypoxia stimulates erythropoiesis and improves aerobic capacity

PURPOSE The purpose of the study was to examine the effect of a very short intermittent exposure to moderate hypoxia in a hypobaric chamber on aerobic performance capacity at sea level and the erythropoietic response. The effects of hypobaric hypoxia alone and combined with low-intensity exercise were also compared. METHODS Seventeen members of three high-altitude expeditions were exposed to intermittent hypoxia in a hypobaric chamber over 9 d at simulated altitude, which was progressively increased from 4000 to 5500 m in sessions ranging from 3 to 5 h x d(-1). One group (N = 7; HE group) combined passive exposure to hypoxia with low-intensity exercise on a cycle ergometer. Another group (N = 10; H group) was only exposed to passive hypoxia. Before and after the exposure to hypoxia, medical status, performance capacity, and complete hematological and hemorheological profile of subjects were evaluated. RESULTS No significant differences were observed between the two groups (HE vs H) in any of the parameters studied, indicating that hypoxia alone was responsible for the changes. After the acclimation period, a significant increase in exercise time (mean difference: +3.9%; P < 0.01), and maximal pulmonary ventilation (+5.5%; P < 0.05) was observed during the maximal incremental test at sea level. Individual lactate-velocity curves significantly shifted to the right (P < 0.05), thus revealing an improvement of aerobic endurance. A significant increase was found in PCV (42.1-45.1%; P < 0.0001), RBC count (5.16 to 5.79 x 10(6) x mm(-3); P < 0.0001), reticulocytes (0.5 to 1.1%; P < 0.0001) and hemoglobin (Hb) concentration (14.2 to 16.7 g x dL(-1); P < 0.002). CONCLUSIONS It was concluded that short-term hypobaric hypoxia can activate the erythropoietic response and improve the aerobic performance capacity in healthy subjects.

Acclimatization Near Home? Early Respiratory Changes After Short-Term Intermittent Exposure to Simulated Altitude

OBJECTIVE With the ultimate goal of finding a straightforward protocol for acclimatization at simulated altitude, we evaluated the early effects of repeated short-term exposure to hypobaric hypoxia on the respiratory response to exercise in hypoxia. METHODS Nine subjects were exposed to a simulated altitude of 5000 m for 2 hours a day for 14 days. Arterial oxygen saturation (SaO2), expired volume per minute (VE), respiratory rate, tidal volume (VT), and heart rate were measured during rest and during exercise (cycloergometer, at 30% of maximum oxygen consumption at sea level), both in normoxia and at 5000 m of simulated altitude on the first and 15th days. On the same days, blood samples were obtained for hematological tests. RESULTS During exercise in hypoxia, SaO2 rose from 65 to 71% (P = .02), and VE rose from 55.5 to 67.6 L.min-1 (P = .02) due to an increase in VT from 2 to 2.6 L (P = .003). No significant differences were found in any of the variables studied at rest either in normoxia or in hypoxia or in exercise in normoxia after the exposure program. In the second week, changes in packed cell volume and blood hemoglobin concentration were nonsignificant. CONCLUSIONS After short-term intermittent exposure to hypobaric hypoxia, subjects increased their ventilatory response and SaO2 during exercise at simulated altitude. These changes may be interpreted as acclimatization to altitude. The monitoring of ventilatory response and SaO2 during moderate exercise in hypobaric hypoxia may be used to detect the first stages of acclimatization to altitude.

Combined intermittent hypoxia and surface muscle electrostimulation as a method to increase peripheral blood progenitor cell concentration.

BackgroundOur goal was to determine whether short-term intermittent hypoxia exposure, at a level well tolerated by healthy humans and previously shown by our group to increase EPO and erythropoiesis, could mobilize hematopoietic stem cells (HSC) and increase their presence in peripheral circulation.MethodsFour healthy male subjects were subjected to three different protocols: one with only a hypoxic stimulus (OH), another with a hypoxic stimulus plus muscle electrostimulation (HME) and the third with only muscle electrostimulation (OME). Intermittent hypobaric hypoxia exposure consisted of only three sessions of three hours at barometric pressure 540 hPa (equivalent to an altitude of 5000 m) for three consecutive days, whereas muscular electrostimulation was performed in two separate periods of 25 min in each session. Blood samples were obtained from an antecubital vein on three consecutive days immediately before the experiment and 24 h, 48 h, 4 days and 7 days after the last day of hypoxic exposure.ResultsThere was a clear increase in the number of circulating CD34+ cells after combined hypobaric hypoxia and muscular electrostimulation. This response was not observed after the isolated application of the same stimuli.ConclusionOur results open a new application field for hypobaric systems as a way to increase efficiency in peripheral HSC collection.

Management of diabetes at high altitude

Editor,—In response to the leader of Moore et al ,1 we would like to report the results obtained in eight type I diabetic mountaineers who ascended the Aconcagua (6950 m)2 without any significant medical problems. The only climber unable to make the summit, because of a problem not related to diabetes, reached 6700 m. None of the climbers took any drugs to prevent acute mountain sickness (AMS) because of the possible …

Sex-linked differences in pulse oxymetry

The difference between genders has generated increasing interest in recent years. It is well known that women and men show differences in their respiratory system: different red blood cell counts, haemoglobin and 2,3-diphosphoglycerate plasma concentrations. Recently, further differences have been found in the ventilatory response to hypoxia and exercise and the evolution of some respiratory illnesses. In this study it was found that during rest at sea level, the haemoglobin oxygen saturation, as measured by pulse oxymetry, is slightly higher in women than in men (98.6 (SD 1.1)% versus 97.9 (SD 0.9)%; p = 0.001). These findings are consistent with other studies, which found gender differences in the transcutaneous or tissue PaO2. The difference in oxygen saturation is not related to differences in ventilation. The disparity is modest and does not seem to produce great differences in the oxygen content of arterial blood, but combined with the different affinity of haemoglobin for oxygen or different metabolic rate, may play a role in the course of elite competition sports, high altitude ascents or the evaluation of critically ill patients. Further studies are needed to establish the degree, extent and clinical importance of these differences in the saturation of haemoglobin.

Increased blood ammonia in hypoxia during exercise in humans

The effect of acute hypoxia on blood concentration of ammonia ([NH3]b) and lactate ([la−]b) was studied during incremental exercise (IE), and two-step constant workload exercises (CE). Fourteen endurance-trained subjects performed incremental exercise on a cycle ergometer under normoxic (21% O2) and hypoxic (10.4% O2) conditions. Eight endurance-trained subjects performed two-step constant workload exercise at sea level and at a simulated altitude of 5000 m (hypobaric chamber, PB=405 Torr; Po2=85 Torr) in random order. In normoxia, the first step lasted 25 minutes at an intensity of 85% of the individual ventilatory anaerobic threshold (ATvent, ind) at sea level. This reduced workload was followed by a second step of 5 minutes at 115% of their ATvent, ind. This test was repeated into a hypobaric chamber, at a simulated altitude of 5,000 m. The first step in hypoxia was at an intensity of 65% of ATvent, ind., whereas workload for the second step at simulated altitude was the same as that of the first workload in normoxia (85% of ATvent, ind). During IE, [NH3]b and [la−]b were significantly higher in hypoxia than in normoxia. Increases in these metabolities were highly correlated in each condition. The onset of [NH3]b and [la−]b accumulation occurred at different exercise intensity in normoxia (181W for lactate and 222W for ammonia) and hypoxia (100W for lactate and 140W for ammonia). In both conditions, during CE, [NH3]b showed a significant increase during each of the two steps, whereas [la−]b increased to a steady-state in the initial step, followed by a sharp increase above 4 mM·L−1 during the second. Although exercise intensity was much lower in hypoxia than in normoxia, [NH3]b was always higher at simulated altitude. Thus, for the same workload, [NH3]b in hypoxia was significantly higher (p<0.05) than in normoxia. Our data suggest that there is a close relationship between [NH3]b and [la−]b in normoxia and hypoxia during graded intensity exercises. The accumulation of ammonia in blood is independent of that of lactate during constant intense exercise. Hypoxia increases the concentration of ammonia in blood during exercise.ResumenSe estudia el efecto de la hipoxia aguda en las concentraciones de amonio ([NH3]b) y lactato ([la−]b) en sangre mediante dos tests diferentes de ejercicio: con aumento progresivo de la carga (IE) y con carga constante en dos escalones (CE). Catorce corredores de fondo realizaron el test IE en un cicloergómetro bajo condiciones de normoxia (21% O2) e hipoxia (10,4% O2), comenzando con una carga de 100W con aumentos progresivos de 25W cada 4 minutos hasta el agotamiento. Otros ocho corredores de fondo realizaron el test CE de un escalón de 25 min seguido de otro de 5 min, a nivel del mar y a una altitud simulada de 5000 m (en cámara hipobárica; PB=405 Torr, PO2=85 Torr) en un cicloergómetro. A nivel del mar, el primer escalón se realizaba a intensidad 85% del umbral anaeróbico ventilatorio individual (ATvent, ind), y sin interrupción, el segundo escalón se realizaba a intensidad 115% del ATvent, ind. En hipoxia, el primer escalón se realizaba a intensidad 65% del ATvent, ind, mientras que la carga para el segundo escalón era la misma que la del primer escalón en normoxia (85% del ATvent, ind). Durante el test IE, la [NH3]b y [la−]b son significativamente mayores en hipoxia que en normoxia, con estrecho paralelismo entre ambos metabolitos tanto en normoxia como en hipoxia. El inicio de la acumulación de [NH3]b y [la−]b ocurre a intensidades de ejercicio diferentes en normoxia (181 W para el lactato y 222 W para el amonio) e hipoxia (100 W para el lactato y 140 W para el amonio). Durante el test CE, la [NH3]b aumenta de forma significativa y gradual durante cada uno de los dos escalones, mientras que [la−]b aumenta sólo ligeramente durante el primer escalón, seguido de un marcado aumento, por encima de los 4 mM·L−1, durante el primer escalón, seguido de un marcado aumento, por encima de los 4 mM·L−1, durante el segundo, en normoxia e hipoxia. Aunque la intensidad del ejercicio es menor en hipoxia que en normoxia, la [NH3]b es siempre superior en hipoxia, de modo que, a igual carga, la [NH3]b en hipoxia es significativamente mayor (p<0,05) que en normoxia. Nuestros datos sugieren la existencia de una estrecha relación entre [NH3]b y [la−]b en normoxia e hipoxia para ejercicios de intensidad progresiva, mientras que la [NH3]b es independiente de [la−]b durante un ejercicio intenso y constante. La hipoxia incrementa la concentración de amonio en sangre durante el ejercicio.

Diabetic Retinopathy at High Altitude

The objective of this study was to determine whether altitude hypoxia favors the development of diabetic retinopathy (DR) in healthy type 1 diabetic climbers with tight glycemia control. The retinas of 7 type 1 diabetic climbers with a history of stays at high altitude were studied through nonmydriatic chamber retinography (Ffo-CNM). The retinographies were performed before and after a 7,143 m peak expedition. One of the subjects presented evidence of DR prior to the ascent, in addition to a microhemorrhage afterward; the rest of the retinographies were normal. Fine glycemia management and adequate acclimatization are not the only cautions for diabetics going to altitude; an ophthalmologic exam beforehand is also recommended.

Combined intermittent hypobaric hypoxia and muscle electro-stimulation: a method to increase circulating progenitor cell concentration?

BackgroundOur goal was to test whether short-term intermittent hypobaric hypoxia (IHH) at a level well tolerated by healthy humans could, in combination with muscle electro-stimulation (ME), mobilize circulating progenitor cells (CPC) and increase their concentration in peripheral circulation.MethodsNine healthy male subjects were subjected, as the active group (HME), to a protocol involving IHH plus ME. IHH exposure consisted of four, three-hour sessions at a barometric pressure of 540 hPa (equivalent to an altitude of 5000 m). These sessions took place on four consecutive days. ME was applied in two separate 20-minute periods during each IHH session. Blood samples were obtained from an antecubital vein on three consecutive days immediately before the experiment, and then 24 h, 48 h, 4 days, 7 days and 14 days after the last day of hypoxic exposure. Four months later a control study was carried out involving seven of the original subjects (CG), who underwent the same protocol of blood samples but without receiving any special stimulus.ResultsIn comparison with the CG the HME group showed only a non-significant increase in the number of CPC CD34+ cells on the fourth day after the combined IHH and ME treatment.ConclusionCPC levels oscillated across the study period and provide no firm evidence to support an increased CPC count after IHH plus ME, although it is not possible to know if this slight increase observed is physiologically relevant. Further studies are required to understand CPC dynamics and the physiology and physiopathology of the hypoxic stimulus.

Age and sex differences in perioperative myocardial infarction after cardiac surgery

We investigate age and sex differences in acute myocardial infarction (AMI) after cardiac surgery in a prospective study of 2038 consecutive patients undergoing cardiac surgery with cardiopulmonary bypass. An age of ≥ 70 years implied changes in the type of AMI from the ST-segment elevation myocardial infarction (STEMI) to non-ST-segment elevation myocardial infarction (non-STEMI). Men were more likely than women to suffer from AMI after cardiac surgery (11.8% vs. 5.6%), as a result of the higher frequency of STEMI (6% of men vs. 1.8% of women; P < 0.001) in both age groups. A troponin-I (Tn-I) peak was significantly higher in patients ≥ 70 years old. In-hospital mortality was higher in patients ≥ 70 (7.3%) than in those < 70 years old (3.3%), because of the increased mortality observed in men with non-AMI (2.1% vs. 6.3%) and women with STEMI (0% vs. 28.6%) and non-STEMI (0% vs. 36.8%, P < 0.05). Old age was associated with a higher frequency of non-STEMI, Tn-I peak, mortality and length of stay in the intensive care unit (ICU). Regardless of age, men more often suffer from AMI (particularly STEMI). AMI in women had a notable impact on excess mortality and ICU stay observed in patients ≥ 70 years of age. Clinical and Tn-I peak differences are expected in relation to age and gender after AMI post-cardiac surgery.