Training-induced increases in sea-level performance are enhanced by acute intermittent hypobaric hypoxia

The goal of this study was to investigate to what extent intermittent exposure to altitude in a hypobaric chamber can improve performance at sea-level. Over a 10-day period, elite male triathletes trained for 2 h each day on a cycle ergometer placed in a hypobaric chamber. Training intensity was 60–70% of the heart rate reserve. Eight subjects trained at a simulated altitude of 2.500 m (hypoxia group), the other eight remained at sea-level (sea-level group). Baseline measurements were done on a cycle ergometer at sea-level, which included an incremental test until exhaustion and a Wingate Anaerobic Test. Nine days after training in hypoxia, significant increases were seen in all important parameters of the maximal aerobic as well as the anaerobic test. A significant increase of 7.0% was seen in the mean maximal oxygen uptake per kilogram body weight ( ), and the mean maximal power output per kilogram body weight (W _max) increased significantly by 7.4%. The mean values of both mean power per kilogram body weight and peak power per kilogram body weight increased significantly by 5.0%, and the time-to-peak decreased significantly by 37.7%. In the sea-level group, no significant changes were seen in the above-mentioned parameters of both the maximal aerobic and the maximal anaerobic test at the second post-test. The results of this study indicate that intermittent hypobaric training can improve both the aerobic and the anaerobic energy-supply systems. Electronic Publication     

Effects of physical training in a hypobaric chamber on the physical performance of competitive triathletes

The effects of training in a hypobaric chamber on aerobic metabolism were studied in five high performance triathletes. During 3 weeks, the subjects modified their usual training schedule (approximately 30 h a week), replacing three sessions of bicycling exercise by three sessions on a cycle ergometer in a hypobaric chamber simulating an altitude of 4,000 m (462 mm Hg). Prior to and after training in the hypobaric chamber the triathletes performed maximal and submaximal exercise in normoxia and hypoxia (462 mm Hg). Respiratory and cardiac parameters were recorded during exercise. Lactacidaemia was measured during maximal exercise. Blood samples were drawn once a week to monitor blood cell parameters and erythropoetin concentrations. Training in the hypobaric chamber had no effect on erythropoiesis, the concentrations of erythropoetin always remaining unchanged, and no effect on the maximal oxygen uptake ( O_2max) and maximal aerobic capacity measured in normoxia or hypoxia. Submaximal performance increased by 34% during a submaximal exhausting exercise performed at a simulated altitude of 2,000 m. During a submaximal nonexhausting test, ventilation values tended to decrease for similar exercise intensities after training in hypoxia. The changes in these parameters and the improved performance found for submaximal exercise may have been the result of changes taking place in muscle tissue or the result of training the respiratory muscles.     

Ventilatory response to acute hypoxia in transgenic mice over-expressing erythropoietin: effect of acclimation to 3-week hypobaric hypoxia

We used transgenic mice constitutively over-expressing erythropoietin ("tg6" mice) and wild-type (wt) mice to investigate whether the high hematocrit (hct), consequence of Epo over-expression affected: (1) the normoxic ventilation (V (E)) and the acute hypoxic ventilatory response (HVR) and decline (HVD), (2) the increase in ventilation observed after chronic exposure to hypobaric hypoxia (430mmHg for 21 days), (3) the respiratory "blunting", and (4) the erythrocythemic response induced by chronic hypoxia exposure. V (E) was found to be similar in tg6 and wt mice in normoxia (FIO2=0.21). Post-acclimation V (E) was significantly elevated in every time point in wt mice at FIO2=0.10 when compared to pre-acclimation values. In contrast, tg6 mice exhibited a non-significant increase in V (E) throughout acute hypoxia exposure. Changes in V (E) are associated with adjustments in tidal volume (V(T)). HVR and HVD were independent of EE in tg6 and wt mice before chornic hypoxia exposure. HVR was significantly greater in wt than in tg6 mice after chronic hypoxia. After acclimation, HVD decreased in tg6 mice. Chronic hypoxia exposure caused hct to increase significantly in wt mice, while only a marginal increase occurred in the tg6 group. Although pre-existent EE does not appear to have an effect on HVR, the observation of alterations on V(T) suggests that it may contribute to time-dependent changes in ventilation and in the acute HVR during exposure to chronic hypoxia. In addition, our results suggest that EE may lead to an early "blunting" of the ventilatory response.     

The effect of intermittent training in hypobaric hypoxia on sea-level exercise: a cross-over study in humans

The purpose of this study was to examine the effect of intermittent training in a hypobaric chamber on physical exercise at sea level. Over a 10 day period, 16 male triathletes trained for 2 h each day on a cycle ergometer placed in a hypobaric chamber. Training intensity was at 60%–70% of the heart rate reserve. There were 8 subjects who trained at a simulated altitude of 2,500 m, the other 8 trained at sea level. A year later, a cross-over study took place. Baseline measurements were made on a cycle ergometer at sea level, which included an incremental test until exhaustion and a Wingate Anaerobic Test. Altogether, 12 subjects completed the cross-over study. At 9 days after training in hypoxia, significant increases were seen in maximal power output ( )(5.2%), anaerobic mean power (4.1%), and anaerobic peak power (3.8%). A non-significant increase in maximal oxygen uptake (V˙O_2max) of 1.9% was observed. At 9 days after training at sea level, no significant changes were seen in (2.1%), V˙O_2max (2.0%), anaerobic mean power (0.2%) and anaerobic peak power (0.2%). When comparing the results of the two training regimes, the anaerobic mean power was the only variable that showed a significantly larger increase as a result of training at altitude. And, although the differences in percentage change between the two training protocols were not significant, they were substantial for as well as for anaerobic peak power. The results of this study indicate that intermittent hypobaric training can improve the anaerobic energy supplying system, and also, to a lesser extent, the aerobic system. It can be concluded that the overall results of the cross-over study showed predominantly improvements in the anaerobic metabolism at variance with the previous study of our own group, where the relative V˙O_2max and increased by 7%. Electronic Publication     

Pre-adaptation,adaptation and de-adaptation to high altitude in humans: cardio-ventilatory and haematological changes

The aim of this study was first to investigate cardio-ventilatory and haematological responses induced by intermittent acclimation and second to study de-adaptation from high altitude observed after descent. To achieve these objectives nine subjects were submitted to intermittent acclimation in a low barometric chamber (8 h daily for 5 days, day 1 at 4500 m, day 5 at 8500 m) before an expedition to the Himalayas. Cardio-ventilatory changes were measured during a hypobaric poikilocapnic hypoxic test (4500 m, barometric pressure = 589 hPa) and haematological changes were studied at sea level. These measurements were performed before and after acclimation, after return to sea level, but also 1 and 2 months after the expedition. In addition, partial pressures of oxygen and carbon dioxide in arterial blood (P _aO₂, P _aCO₂) and arterial erythropoietin concentration [EPO] were measured at rest during the hypoxic test. Results suggested the pre-adaptation protocol was efficient since an increased P _aO₂ (+12%, P < 0.05), a smaller difference in alveolo-arterial P0₂ ( –63%, P < 0.05) and a lower P _aCO₂ ( –11%, P < 0.05), subsequent to ventilatory changes, were observed after acclimation with a significant increase in reticulocytes and in sea level [EPO] (+44% and +62% respectively, P < 0.05). Deadaptation was characterized by a loss of these cardioventilatory changes 1 month after descent, whereas the haematological changes (increased red blood cells and packed cell volume, P < 0.05) persisted for 1 month before disappearing 2 months after descent. This study would also suggest that acute hypoxia performed after a sojourn at high altitude could induce significantly depressed EPO responses (P < 0.05).     

Diurnal normobaric moderate hypoxia raises serum erythropoietin concentration but does not stimulate accelerated erythrocyte production

This study was performed to examine the effect of diurnal normobaric hypoxia on hematological parameters. Eleven healthy male volunteers were randomly selected to be in either the hypoxic group (n=6) or the control group (n=5). The hypoxic group was exposed to 8 h of normobaric hypoxia in hypoxic tent systems that elicited a target peripheral O₂ saturation of 81±2% on three consecutive days. The control group spent three consecutive 8-h days in modified tent systems that delivered normoxic air into the tent. Venous blood samples were collected before the exposure (days –5, 0), after each day of the exposure (days 1, 2, 3), and for 3 weeks after the exposure (days 7, 10, 13, 17, 24). Serum erythropoietin concentration significantly increased from 9.1±3.3 U·L⁻¹ to 30.7±8.6 U·L⁻¹ in the hypoxic group. Although there were significant increases in hematocrit (4%), hemoglobin concentration (5%), red blood cell count (4%) on day 7 in the hypoxic group, these observations were likely due to dehydration or biological variation over time. There was no significant change in early erythropoietic markers (reticulocyte counts or serum ferritin concentration), which provided inconclusive evidence of accelerated erythroid differentiation and proliferation. The results suggest that the degree of hypoxia was sufficient to stimulate increased erythropoietin production and release. However, the duration of hypoxic exposure was insufficient to propagate the erythropoietic cascade.     

Temporal pattern of erythropoietin titers in kidney tissue during hypoxic hypoxia

Plasma titers of erythropoietin (Ep) are known to increase initially during hypoxia and to return then towards prehypoxia values. To find out if this pattern of plasma Ep might be related to changes in the production of the hormone, I have compared plasma with kidney Ep titers in hypoxic rats. Rats were exposed to hypoxia in a hypobaric chamber at 0.42 atm for various time intervals for up to 4 days. Kidney Ep titers were assayed in extracts from kidneys that had been flushed free of blood in situ. It was found that kidneys of normal rats do not store significant amounts of Ep. Kidney Ep titers increased transiently during hypoxia. They reached maximum values after 6h and then declined to almost undetectable levels at continued hypoxia. In the plasma, maximum values were found after 12–18h of hypoxia. Additional studies were done on the effects of discontinuous hypoxia. It was found that, even after 3 days of previous hypoxia exposure, plasma and kidney Ep titers increased again in rats when these were maintained intermittently in normoxia for 18 h.It is concluded that the rise and fall in plasma Ep titers during hypoxia reflect similar changes in kidney Ep production.Supported by grants from the Deutsche Forschungsgemeinschaft (Je 95/3 and SFB 43)     

Demonstration of high levels of erythropoietin in rat kidneys following hypoxic hypoxia

Controversial hypotheses exist as to whether hypoxic kidneys produce biologically active erythropoietin (Ep) or an inactive erythropoietic factor that generates Ep from plasma protein in the blood. To clarify the role of the kidney in Ep production we attempted to extract Ep from kidneys of normal and of hypoxia exposed (6 h at 0.42 atm) Sprague-Dawley rats. Ep was measured in the microsomal fraction of kidney homogenates, using the exhypoxic polycythemic mouse assay for Ep. The Ep content was also determined in kidneys that were flushed free of blood with isotonic phosphate-buffer prior to extirpation.We found 0.04 U Ep/g in blood-depleted kidneys of normal rats. Upon exposure of the animals to hypoxia the Ep level increased to 0.92 U/g kidney. Ep levels were significantly higher in the kidney cortex than in the medulla. The erythropoietic activity in renal extracts was not enhanced after incubation of samples with homologous serum. Ep extracted from hypoxic kidneys behaved identically with plasma-Ep in the following biochemical tests: heat stability, affinity chromatography with wheat germ lectin, ion exchange chromatography, molecular sieve chromatography and neuraminidase inactivation.These studies support the hypothesis that kidney cortex cells are capable of producing biologically active Ep.Supported by grants from the Deutsche Forschungsgemeinschaft (Je 95/3 and SFB 43).Some of the material reported in this paper was presented in preliminary form at the 54. Meeting of the German Physiological Society (Bauer and Jelkmann 1981).     

Erythropoietin protects cultured cortical neurons, but not astroglia, from hypoxia and AMPA toxicity

In addition to its better-known hemopoietic action, erythropoietin (Epo) has neurotrophic properties and neuroprotective effects in some models of hypoxic-ischemic injury. To define further the cellular mechanisms underlying neuroprotection by Epo, we studied the effects of Epo on hypoxia with glucose deprivation in cultured rat cortical neurons and astroglia and on exposure to excitotoxins in cultured rat cortical neurons. Epo (30 pM) reduced neuronal, but not astroglial, cell death from hypoxia with glucose deprivation, and also attenuated the neurotoxic effect of (±)--amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), but not other excitotoxins. Epo appears to protect against cerebral ischemia through a direct effect on neurons that may be mediated in part by AMPA receptors.     

Venous but not skeletal muscle interstitial nitric oxide is increased during hypobaric hypoxia

Systemic hypoxia leads to peripheral vasodilation that serves to counteract the decrease in peripheral oxygen (O₂) delivery. Skeletal muscle vasodilation associated with hypoxia is due to release of vasodilator substances such as adenosine and/or nitric oxide (NO). We hypothesized that skeletal muscle may act as a source of NO during exposure to hypoxia. Therefore, we measured NO in forearm venous plasma and in skeletal muscle interstitial dialysate in seven healthy young men during exposure to simulated altitude of 2,438 and 4,877 m (20 min at each level) in a hypobaric chamber. O₂ saturation (mean ± SEM) fell from 98.0 ± 0.2% at ambient conditions to 91.0 ± 0.4% at 2,438 m and to 73.2 ± 4.4% at 4,877 m (P < 0.05). While blood pressure remained unchanged, heart rate increased in a graded fashion (P < 0.05). Plasma NO (chemiluminescence method) rose from 11.6 ± 1.3 to 16.9 ± 2.9 μM at 2,438 m (P < 0.05) but remained similar at 16.4 ± 2.3 μM at 4,877 m (NS). In contrast, skeletal muscle microdialysate NO levels were lower than plasma NO (P < 0.01) and did not change during simulated altitude. Thus, hypoxia produced by simulated high altitude exposure leads to an increase in plasma but not skeletal muscle interstitial NO. These data support an important role of NO in the peripheral vascular responses to hypoxia. The differential responses of plasma vs. interstitial NO during hypoxia suggest an endothelial or intravascular source of NO.     

Erythropoietin response to acute hypobaric or anaemic hypoxia in gentamicin-administered rats

In an attempt to assess the erythropoietin (Epo) production site(s) in rat kidney, Epo response to hypoxia and renal histopathological changes were studied in rats administered with graded doses of gentamicin. Male Sprague-Dawley rats of 9 to 11 weeks old were used. Following a 14-day subcutaneous administration (67.5 or 33.8 mg kg^-1 day^-1) of gentamicin, a nephrotoxic aminoglycoside, selective proximal tubular lesions were produced. These gentamicin-administered rats were compared with normal rats with respect to Epo response to hypoxia. Two different kinds of hypoxic load, either 0.35 atm hypobaric hypoxia (P_IO2= 46 torr) or acute anaemia (Ht: 29.3 ± 0.2% and [Hb]: 9.7 ± 0.3 g dl^-1) by withdrawing of blood corresponding to 1–2% of body weight was used. During the hypoxic period of up to 48 h, the peak renal venous plasma Epo titres of 3.1 ± 0.6 and 4.3 ± 0.6 U ml^-1 was observed at the 6th h in normal hypobaric hypoxic and anaemic rats, compared with the prehypoxic value of 0.7 ± 0.1 U ml^-1. The Epo titres then declined gradually. In the rats which were administered gentamicin, Epo response pattern was the same as that observed in the normal rats, but the peak value decreased significantly to 0.8 ± 0.3 and 1.1 ± 0.4 U ml^-1 in hypoxic and anaemic rats (P < 0.05). Histological examination revealed the selective damage to renal proximal convoluted tubules. The Epo response was reduced by the tissue damages, and restoration of the gentamicin-induced tissue injury was accompanied with restored Epo response to hypoxia. The results suggest that renal proximal convoluted tubules are involved in Epo production under hypoxia.     

Maximal oxygen uptake and erythropoietic responses after training at moderate altitude

Summary Six well-trained male cross-country skiers trained for 7 days at 2700 m above sea level, their accommodation being at 1695 m. Blood samples for haemoglobin concentration [Hb], erythropoietin concentration [EPO] and reticulocyte count were collected before, during and after altitude exposure. Packed cell volume (PCV), red blood cell count (RBC), transferrin-iron saturation, mean red cell volume (MCV), mean corpuscular haemoglobin concentration (MCHC), maximal oxygen uptake, maximal achieved ventilation and heart rate were determined pre- and postaltitude exposure. The [EPO] increased significantly from prealtitude (mean 36 mU·ml^–1, SD 5) to maximal altitude values (mean 47 mU·ml^–1, SD 3). The [Hb] had increased significantly above pre-altitude values (mean 8.8 mmol·l^–1, SD 0.5) on day 2 (mean 9.1 mmol·l^–1, SD 0.4) and day 7 (mean 9.4 mmol·l^–1, SD 0.4) at altitude and on day 4 postaltitude (mean 9.2 mmol·l^–1, SD 0.4). The reticulocyte counts had increased significantly above pre-altitude values (mean 6, SD 3) on day 3 at altitude (mean 12, SD 8) and day 4 postaltitude (mean 10, SD 5). The RBC counts had increased on the 4th postaltitude day. The transferrin-iron saturation had decreased below pre-altitude values (mean 23%, SD 4%) on day 4 postaltitude (mean 14%, SD 5%) and had increased on day 11 postaltitude (mean 22%, SD 7%). There were no significant changes in MCV, MCHC, PCV, maximal oxygen uptake and maximal achieved ventilation, and heart rate pre- to postaltitude. These observations demonstrated an erythropoietic response to the altitude training which was not sufficient to increase the postaltitude maximal oxygen uptake.     

Human erythropoietin response to hypocapnic hypoxia,normocapnic hypoxia,and hypocapnic normoxia

This study investigated the human erythropoietin (EPO) response to short-term hypocapnic hypoxia, its relationship to a normoxic or hypoxic increase of the haemoglobin oxygen affinity, and its suppression by the addition of CO₂ to the hypoxic gas. On separate days, eight healthy male subjects were exposed to 2 h each of hypocapnic hypoxia, normocapnic hypoxia, hypocapnic normoxia, and normal breathing of room air (control experiment). During the control experiment, serum-EPO showed significant variations (ANOVAP = 0.047) with a 15% increase in mean values. The serum-EPO measured in the other experiments were corrected for these spontaneous variations in each individual. At 2 h after ending hypocapnic hypoxia (10% O₂ in nitrogen), mean serum-EPO increased by 28% [baseline 8.00 (SEM 0.84) U · 1⁻¹, post-hypoxia 10.24 (SEM 0.95) U · 1⁻¹, P = 0.005]. Normocapnic hypoxia was produced by the addition of CO₂ (10% Co₂ with 10% O₂) to the hypoxic gas mixture. This elicited an increased ventilation, unaltered arterial pH and haemoglobin oxygen affinity, a lower degree of hypoxia than during hypocapnic hypoxia, and no significant changes in serum-EPO (ANOVAP > 0.05). Hypocapnic normoxia, produced by hyperventilation of room air, elicited a normoxic increase in the haemoglobin oxygen affinity without changing serum-EPO. Among the measured blood gas and acid-base parameters, only the partial pressures of oxygen in arterial blood during hypocapnic hypoxia were related to the peak values of serum-EPO (r = −0.81,P = 0.01). The present human EPO responses to hypoxia were lower than those which have previously been reported in rodents and humans. In contrast with the earlier rodent studies, it was found that human EPO production could not be triggered by short-term increases in pH and haemoglobin oxygen affinity per se, and the human EPO response to hypoxia could be suppressed by concomitant normocapnia without acidosis.     

Metabolic response during intermittent graded sprint running in moderate hypobaric hypoxia in competitive middle-distance runners

The purpose of this study was to determine whether the metabolic response and running performance during intermittent graded sprint running were affected by moderate hypobaric hypoxia (H; 2,500 m above sea level) in competitive middle-distance runners. Nine male runners performed intermittent graded sprint running until exhaustion, to evaluate the metabolic response and running performance in H and normobaric normoxia (N). The test constructed of incremental (25 m min⁻¹) 20 s running bouts (4° inclination) interspaced with 100 s recovery periods. Maximal running speed was not different between conditions [453 (7) m min⁻¹ vs. 458 (4) m min⁻¹ in N vs. H]. at each speed was lower in H than N (ANOVA; P < 0.05). Although, oxygen deficit at each speed was not different between N and H (ANOVA; P = 0.1), total accumulated in all bouts was significantly higher in H than N [165 (10) ml kg⁻¹ in N and 173 (10) ml kg⁻¹ in H]. The ratio of was similar in all bouts, but higher in H than N. These results suggest that intermittent graded sprint running performance is not affected by moderate hypobaria despite a reduction in the energy supplied by aerobic metabolism due to a compensatory increase in the energy supplied by the anaerobic metabolism in competitive middle-distance runners.     

Decreased feeding associated with acute hypoxia in rats

Rats obtained less food than normal on a cyclic-ratio schedule during brief, 1-hr exposure to either moderate hypobaric hypoxia (BP=435 Torr, PO₂≈91 Torr) or to hypoxic hypoxia (BP=750 Torr, PO₂≈90 Torr), but not during hypobaric exposure with 36.5% oxygen (BP=435 Torr, PO₂≈159 Torr). The depressed rate of feeding associated with hypoxia was nevertheless well regulated. Interpreted in terms of a regulatory model, these results suggest that hypoxia suppresses eating because it degrades the taste of food, not because it impairs feeding regulation or general activity.     

Hemodynamic responses to hypoxia and hyperoxia in calves at sea level and altitude

Summary Hemodynamic studies were done in nine male Holstein calves, born at sea level, at 250 m (P _B 740 mm Hg) and in eight of these calves after 2 and 4 weeks at 3400 m altitude (P _B 510 mm Hg). Cardiac index (CI) decreased significantly as compared to sea level after 2 weeks at altitude and it was further decreased after 4 weeks. This reduction in CI resulted from decreased stroke index (SI) with unchanged heart rate (HR). Mean pulmonary arterial pressure (PAM) rose from 26 mm Hg at sea level to 63 and 74 mm Hg after 2 and 4 weeks at 3400 m, respectively. Both pulmonary arterial systolic and diastolic pressures were substantially increased at altitude, the diastolic relatively more than the systolic pressure (4.5 fold increase vs. 2.5 fold). Aortic blood pressures (systolic, diastolic and mean) did not change significantly at 3400 m. Right ventricular (systolic) and atrial (mean) pressures increased at altitude.During acute severe hypoxia (P _{IO 2} 55 mm Hg) at sea level CI remained essentially unchanged, while SI and HR, respectively, decreased and rose significantly; PAM was double the normoxic value. Acute hypoxia after 4 weeks at 3400 m did not elicit significant changes in blood gases and pH, CI, SI and HR while PAM increased by 25 mm Hg. There were slight reductions in CI, SI, HR and PAM during acute hyperoxia at sea level. Hyperoxia after 4 weeks at altitude did not change CI, while SI rose significantly; PAM decreased by 30 mm Hg. Apparently, the Holstein calf has a highly reactive pulmonary vascular bed to acute and chronic hypoxia which could make this cattle breed more susceptible to right heart failure during exposure to chronic hypoxia at high altitude.     

Enzymatic responses and adaptations to swimming training and hypobaric hypoxia in postnatal rats

Twenty four male Sprague-Dawley rats, 35 days old, were randomly assigned to one of four groups: 2 resting control groups and 2 swimming groups. The sea level-control and the sea level-swimming groups were housed 5 weeks at 1,011 hPa (760 mmHg) while the hypoxic control and swimming groups were housed for 1 week at 678 hPa, followed by 4 weeks at 611 hPa. The swimming rats were subjected to a swimming program of 30 min, 6 days/week for 5 weeks. Both hypoxia groups developed significantly higher Hb and Hct levels than the sea level groups. The glycogen content in the extensor digitorum longus (EDL) and the deep portion of the vastus lateralis (DVL) muscles of the sea level-swimming group were significantly greater as compared to the hypoxia swimming group. The succinate dehydrogenase (SDH) activity in the sea level-control group was significantly lower in the EDL muscle than in the 3 other groups, and in the DVL muscle lower than that of the sea level-swimming group. Histochemically, hypoxia and swimming training induced significant increases in the fast-twitch-oxidative-glycolytic (FOG) fibers (6-11%) in soleus muscle, and decreases in the slow-twitch-oxidative (SO) fibers. The EDL muscles had significantly higher percentages of FOG fibers in the hypoxia and swimming groups than in the sea level-control group. On the basis of the present study it seems probable that hypoxia is a triggering factor for the conversions of muscle fiber types and the increase in oxidative capacity.     

Epo deficiency alters cardiac adaptation to chronic hypoxia

The involvement of erythropoietin in cardiac adaptation to acute and chronic (CHx) hypoxia was investigated in erythropoietin deficient transgenic (Epo-TAg^h) and wild-type (WT) mice. Left (LV) and right ventricular functions were assessed by echocardiography and hemodynamics. HIF-1α, VEGF and Epo pathways were explored through RT-PCR, ELISA, Western blot and immunocytochemistry. Epo gene and protein were expressed in cardiomyocytes of WT mice in normoxia and hypoxia. Increase in blood hemoglobin, angiogenesis and functional cardiac adaptation occurred in CHx in WT mice, allowing a normal oxygen delivery (O₂T). Epo deficiency induced LV hypertrophy, increased cardiac output (CO) and angiogenesis, but O₂T remained lower than in WT mice. In CHx Epo-TAg^h mice, LV hypertrophy, CO and O₂T decreased. HIF-1α and Epo receptor pathways were depressed, suggesting that Epo-TAg^h mice could not adapt to CHx despite activation of cardioprotective pathways (increased P-STAT-5/STAT-5). HIF/Epo pathway is activated in the heart of WT mice in hypoxia. Chronic hypoxia induced cardiac adaptive responses that were altered with Epo deficiency, failing to maintain oxygen delivery to tissues.     

Normo or hypobaric hypoxic tests: propositions for the determination of the individual susceptibility to altitude illnesses

Assessment of individual susceptibility to altitude illnesses and more particularly to acute mountain sickness (AMS) by means of tests performed in normobaric hypoxia (NH) or in hypobaric hypoxia (HH) is still debated. Eighteen subjects were submitted to HH and NH tests (PIO₂=120 hPa, 30 min) before an expedition. Maximal and mean acute mountain sickness scores (AMSmax and mean) were determined using the self-report Lake Louise questionnaire scored daily. Cardio-ventilatory (f, V_T, PetO₂ and PetCO₂, HR and finger pulse oxymetry SpO₂) were measured at times 5 and 30 min of the tests. Arterial (PaO₂, PaCO₂, pH, SaO₂) and capillary haemoglobin (Hb) measurements were performed at times 30 min. Hypoxic ventilatory (HVR) and cardiac (HCR) responses, peripheral O₂ blood content (CpO₂) were calculated. A significant time effect is found for ΔSpO₂ (P = 0.04). Lower PaCO₂ (P = 0.005), SaO₂ (P = 0.07) and higher pH (P = 0.02) are observed in HH compared to NH. AMSmax varied from 3 to12 and AMSmean between 0.6 and 3.5. In NH at 30 min, AMSmax is related to PetO₂ (R = 0.61, P = 0.03), CpO₂ (R = −0.53, P = 0.02) and in HH to CpO₂ (R = −0.57, P = 0.01). In NH, AMSmean is related to Δf (R = 0.46, P = 0.05), HCR (R = 0.49, P = 0.04), CpO₂ (R = −0.51, P = 0.03) and, in HH at 30 min, to V_T (R = 0.69, P = 0.01) and a tendency for CpO₂ (R = −0.43, P = 0.07). We conclude that HH and NH tests are physiologically different and they must last 30 min. CpO₂ is an important variable to predict AMS. For practical considerations, NH test is proposed to quantify AMS individual susceptibility using the formulas: AMSmax = 9.47 + 0.104PetO₂(hPa)–0.68CpO₂ (%), (R = 0.77, P = 0.001); and AMSmean = 3.91 + 0.059Δf + 0.438HCR–0.135CpO₂ (R = 0.71, P = 0.017).     

Haematopoietic and right ventricular response to intermittent hypobaric hypoxia in meat-type chickens

The purpose of this study was to examine the effect of simulated high altitude (2054 m) on erythropoiesis and pulmonary hypertension-induced right ventricular hypertrophy. Broiler chickens were reared at atmospheric pressure (altitude 295 m) or in a hypobaric chamber at an atmospheric pressure of 592 mmHg (calculated partial pressure of oxygen: 124 mmHg; calculated altitude and O(2) equivalents: 2054 m and 16.3%) for 2-, 4-, 8- or 16-h periods out of each 24 h. Hypoxia of 2 and 4 h per day had little effect on blood parameters although there was some indication of right ventricular hypertrophy. Hypoxia of 8 or 16 h produced significantly higher haematocrit and haemoglobin levels than controls, and there was moderate to marked right ventricular hypertrophy. The relationship between right ventricular hypertrophy and duration of hypoxia was greater than between polycythaemia and duration of hypoxia.