Teresa Pagès

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.

Muscle myoglobin and flying habits in birds

Abstract 1. 1. The myoglobin (Mb) content of different muscles (heart, pectoral, wing, thigh and gastrocnemius) in chickens (New Hampshire strain), quail (Wild quail, Coturnix coturnix coturnix; and farm quail, Coturnix c. japonica), urban pigeons (Columbia livia), starling (Sturnus vulgaris) and seagulls (Larus argentatus and L ridibundus) have been analyzed. 2. 2. Differences in Mb in the same muscle from different species, have been statistically demonstrated. The Mb concentration data (0.59–6.8 mg Hb/g wet muscle) from these species, fits in well with the range in birds, compiled from the literature. 3. 3. Differences in Mb content in the same muscle, from different species, have been statistically shown. However, it is difficult to establish a relationship with flight habits. 4. 4. After only a 2 week captivity in pigeons, the myoglobin content was already significantly reduced in heart, pectoral and wing muscles, but not in the leg muscle.

Seasonal changes in hematology and blood chemistry of the freshwater turtle Mauremys caspica leprosa

Abstract 1. 1. Hematological and some plasma chemistry values were studied in adult stripe-necked terrapins (Mauremys caspica leprosa) in summer and autumn. 2. 2. Differences were detected in hematocrit, red cell count and hemoglobin concentration. However, hematimetric indexes remain unchanged. 3. 3. The erythrocyte dimensions do not change but the nucleus size was significantly lower in autumn turtles. 4. 4. Plasma concentrations of glucose, calcium and magnesium were lower in summer, whereas inorganic phosphorus was higher. 5. 5. Slight variations were also observed in total plasma protein concentration and their fractional composition, and in plasma osmolarity.

Oxidative Stress Status in Rats After Intermittent Exposure to Hypobaric Hypoxia

OBJECTIVE Programs of intermittent hypobaric hypoxia (IHH) exposure are used to raise hemoglobin concentration and erythrocyte mass. Although acclimation response increases blood oxygen transport capacity leading to a VO(2max) increase, the effects of reactive oxygen species (ROS) might determine the behavior of erythrocytes and plasma, thus causing a worse peripheral blood flow. The goals of the study were to establish the hematological changes and to discern whether an IHH protocol modifies the antioxidant/pro-oxidant balance in laboratory rats. METHODS Male rats were subjected to an IHH program consisting of a daily 4-hour session for 5 days/week until completing 22 days of hypoxia exposure in a hypobaric chamber at a simulated altitude of 5000 m. Blood samples were taken at the end of the exposure period (H) and at 20 (P20) and 40 (P40) days after the end of the program, and compared to control (C), maintained at sea-level pressure. Hematological parameters were measured together with several oxidative stress indicators: plasma thiobarbituric acid reactive substances (TBARS) and erythrocyte catalase (CAT) and superoxide dismutase (SOD). RESULTS Red blood cell (RBC) count, hemoglobin concentration and hematocrit were higher in H group as compared to all the other groups (p < 0.001). However, there were no significant differences between the 4 groups in any of the oxidative stress-related parameters. CONCLUSIONS The absence of significant differences between groups indicates that our IHH program has little impact on the general redox status, even in the laboratory rat, which is more sensitive to hypoxia than humans. We conclude that IHH does not increase oxidative stress.

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.

A method for sampling representative muscular venous blood during exercise in rats

A technique for chronic cannulation of the muscular branch of the femoral vein in the rat is described. The method was validated by the application of vascular corrosion casts and comparative analysis of lactate concentration with mixed venous blood and arterial samples taken through the cannulas during lower hindlimb muscle contraction in anaesthetized rats.

Blood Rheology Adjustments in Rats after a Program of Intermittent Exposure to Hypobaric Hypoxia

Intermittent hypobaric hypoxia (IHH) exposure induces a rise in hemoglobin concentration and an increase in erythrocyte mass in both rats and humans. Although this response increases blood oxygen transport capacity, paradoxically, it could impair blood flow and gas exchange because of the blood viscosity alterations associated with the rising hematocrit. In the present study, male rats were subjected to an IHH program consisting of a daily 4-h session for 5 days/week until they had completed 22 days of hypoxia exposure in a hypobaric chamber at a simulated altitude of 5000 m. Blood samples were taken at the end of the exposure period (H) and at 20 (P20) and 40 (P40) days after the end of the program and were compared to control (C) maintained at sea- level pressure. Apparent blood viscosity (eta(a)) and plasma viscosity (eta(p)) were measured in a cone-plate microviscometer. Although the hematocrit significantly increased in the H group, blood apparent viscosity did not differ among groups, ranging from 7.67 to 6.57 mPa*sec at a shear rate of 90 sec(-1). Relative blood viscosity showed a clear increase (about 27%) in H rats, mainly due to the significant decrease in plasma viscosity. This finding could be interpreted as a compensatory response, which reduced the effect of increased erythrocyte mass volume on whole-blood viscosity. Oxygen delivery index and blood oxygen potential transport capacity remained unchanged in all groups. These data indicate that the IHH program has a deep but transitory effect on red cell parameters and a moderate effect on blood rheological behavior.

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.