Cardiovascular responses during hypoventilation at exercise.

This study aimed to determine the cardiovascular responses during a prolonged exercise with voluntary hypoventilation (VH). 7 men performed 3 series of 5-min exercise at 65% of normoxic maximal O (2) uptake under 3 conditions: (1) normal breathing (NB) in normoxia (NB (0.21)), (2) VH in normoxia (VH (0.21)), (3) NB in hypoxia (NB (0.157), inspired oxygen fraction=0.157). In both VH (0.21) and NB (0.157), there was a similar drop in arterial oxygen saturation and arterial O (2) content (CaO (2)) which were lower than in NB (0.21). Heart rate (HR), stroke volume, and cardiac output (-) were higher in VH (0.21) than in NB (0.21) during most parts of exercise whereas there was no difference between NB (0.157) and VH (0.21) or NB (0.21). HR variability analysis suggested an increased sympathetic modulation in VH (0.21) only. O (2) transport and oxygen uptake were generally not different between interventions. Mixed venous O (2) content (C-O (2)) was lower in NB (0.157) than in both VH (0.21) and NB (0.21) and not different between the latter. CaO (2)-C-O (2) was not different between NB (0.157) and NB (0.21) but lower in VH (0.21). This study shows that a prolonged exercise with VH leads to a greater cardiac activity, independent from the hypoxic effect. The greater - in VH compared to normal breathing seems to be the main factor for compensating the drop of arterial oxygen content.

[Adaption to chronic hypoxaemia by populations living at high altitude]. / Adaptation à l'hypoxie chronique des populations de haute altitude.

Permanent life at high altitude induces important physiological stresses linked to the exposure to chronic hypoxia. Various strategies have been adopted by diverse populations living in the Andes, Tibet or East Africa. The main mechanism is an increase in red blood cell production, more marked in Andeans than in Tibetans or Ethiopians. Other changes are observed in the cardiovascular or respiratory systems, as well as in the utero-placental circulation. Sometimes, a de-adaptation process to hypoxia develops, when erythrocytosis becomes excessive and leads to haematological, vascular and cerebral complications (Monge's disease or chronic mountain sickness). Pulmonary hypertension may also appear. Therapeutic options are available but not sufficiently used. Genetic studies have recently been undertaken to try to better understand the evolution of the human genome in populations living in various high altitude regions of the world, as well as the genetic risk factors for chronic diseases. A new model has appeared, intermittent chronic hypoxia, due to the development of economic activities (mainly mining) in desert regions of the Altiplano.

Endothelin receptors blockade blunts hypoxia-induced increase in PAP in humans.

BACKGROUND: Activation of the endothelin-1 (ET-1) pathway may be involved in hypoxia-induced pulmonary vasoconstriction, increase in pulmonary pressure and high altitude pulmonary oedema. Thus, we investigated the effect of the ETA/ETB receptor antagonist, bosentan, on pulmonary artery systolic pressure (PASP) in healthy subjects (n = 10). DESIGN: We used a double-blind, placebo-controlled, randomized, cross-over design to study the effects of a single oral dose of bosentan (250 mg) on PASP after 90-min-exposure to normobaric hypoxia (FiO(2) = 0.12). We measured PASP and cardiac output by echocardiography, systolic arterial blood pressure, arterial O(2) saturation (SaO(2)), and blood gases at rest and during a sub-maximal exercise. RESULTS: PASP in normoxia at rest was 23.5 +/- 2.7 and during exercise 39.8 +/- 11.6 mmHg (P < 0.0001). During the placebo period, hypoxia induced a significant decrease in SaO(2), PaO(2) and PCO(2) and increase in pH. PASP at rest increased significantly: 32.1 +/- 3.5 mmHg (P < 0.001 vs. normoxia). Bosentan significantly blunted the hypoxia-induced increase in PASP: bosentan: 27.0 +/- 3.3 mmHg, P = 0.002 vs. placebo at rest, but not during exercise: bosentan 39.8 +/- 11.6 vs. placebo 43.0 +/- 8.5 mmHg, ns. Bosentan had no effect on the hypoxia-induced changes in blood gases, or on cardiac output and systolic arterial blood pressure, which were not modified by hypoxia. CONCLUSION: A single oral dose of bosentan blunted an acute hypoxia-induced increase in PASP in healthy subjects, without altering cardiac output or systemic blood pressure.

Polar Activity Watch 200: a new device to accurately assess energy expenditure.

OBJECTIVES: Energy expenditure (EE) based on movement detection is calculated by a new device, the Activity Watch 200 (AW200). The aim of this study was to validate EE measured by this device against indirect calorimetry (IC) and to assess the reproducibility of AW200 measurements. DESIGN: EE was assessed during a 9.7 km hike. 10 men and 10 women in the age range 35-45 years, and 5 men and 6 women in the age range 50-55 years were tested. One in five participants of each age- and sex-matched group was equipped with a portable metabograph (Oxycon Mobil) for IC measurements. Data were collected every 30 min during the hike, and IC was extrapolated for the remaining four other participants of the group. RESULTS: During the total hike, there was a high correlation between EE obtained from the AW200 and the IC calculation (r = 0.987, p<0.001). Identical values of EE were calculated by both methods during the first 90 min of the hike. However, EE calculated by the AW200 at 120 min and at the end of the hike was lower (p<0.05). Bland-Altman analysis showed limits of agreements between 105 and 279 kJ after 30 and 120 min, respectively. EE measured by the AW200 was well correlated with IC measurements, and limits of agreement between devices were below 10% of the measured values for hike durations longer than 60 min. CONCLUSION: The AW200 appears to be a very useful and accurate device for measuring EE during exercise in recreational hikers and provides a useful tool for keeping track of personal EE.

[Determining factors of pulmonary function in healthy Tunisian children]. / Déterminants de la fonction pulmonaire chez l'enfant sain en Tunisie.

Introduction Pulmonary function parameters are known to vary with age, sex, height and ethnic extraction. No normal values have been reported for pulmonary function in Tunisian children. Moreover, little attention has been paid to the factors affecting the development of lung function in Tunisian healthy children. State of art Birth weight and height, physical activity level, anthropometric, socioeconomic and environmental factors could influence the development of lung function in healthy children. Perspectives The studies conducted by our group have allowed us 1) to set reference values for spirometry in healthy Tunisian children; 2) to indicate that, in Tunisian adolescents, the use of only one morphological parameter such as height, is not sufficient, but the pubertal status could be taken into account to standardize the lung function and 3) to show the main predictive factors for pulmonary development to be the anthropometric factors such as height, weight, maximal inspiratory and expiratory thoracic perimeter, sex and age, and the environmental conditions (type of heating) in our population of healthy Tunisian children. Conclusion These findings should improve medical surveillance of respiratory diseases, stipulation of preventive and therapeutic measures in Tunisian children.

Factors affecting the development of lung function in Tunisian children.

We undertook to evaluate the impacts of morphology at birth, physical activity, anthropometric, socioeconomic and environmental factors on lung function in healthy Tunisian children. Pulmonary function parameters were measured with a Minato portable spirometer in a randomized population of 756 healthy children (388 males and 368 females) aged between 6 and 16. The morphology at birth, the gestational age, the physical activity, the socioeconomic status, the type of habitation, and the environmental factors were all assessed by a standard questionnaire. Using univariate analysis, we found that: (1) morphometric parameters (height, weight, maximal inspiratory, and expiratory perimeter), as well as sex were highly associated with pulmonary function parameters; (2) Height at birth showed strong significant relations with FVC, FEV(1), and FEV(1)/FVC; (3) lung function parameters were influenced by physical training of our children, socioeconomic status, indoor pollution, and passive smoking; and (4) we did not observe any association between the gestational age and the weight at their birth and lung function parameters. Using a general linear model analysis, morphometric parameters, age, sex, type of heating, and maximal inspiratory and expiratory perimeters had significant relation with respiratory parameters. In our population of healthy Tunisian children, the main predictive factors of the pulmonary development were the morphological factors such as height, weight, maximal inspiratory, and expiratory thoracic perimeter, sex and age, and the environmental conditions such as type of heating but not morphology at birth, physical activity, or socioeconomic status.

Live and/or sleep high:train low, using normobaric hypoxia.

The increase in oxygen transport elicited by several weeks of exposure to moderate to high altitude is used to increase physical performance when returning to sea level. However, many studies have shown that aerobic performance may not increase at sea level after a training block at high altitude. Subsequently, the concept of living high and training low was introduced in the early 1990s and was further modified to include simulated altitude using hypobaric or normobaric hypoxia. Review is given of the main studies that have used this procedure. Hematological changes are limited to insignificant or moderate increase in red cell mass, depending on the "dose" of hypoxia. Maximal aerobic performance is increased when the exposure to hypoxia is at least over 18 days. Submaximal performance and running economy have been found increased in several, but not all, studies. The tolerance (fatigue, sleep, immunological status, cardiac function) is good when the altitude or simulated altitude is not higher than 3000 m. Virtually no data are available about the effect of this procedure upon anaerobic performance. The wide spread of these techniques deserves further investigations.

Brain stem NO modulates ventilatory acclimatization to hypoxia in mice.

The objective of our study was to assess the role of neuronal nitric oxide synthase (nNOS) in the ventilatory acclimatization to hypoxia. We measured the ventilation in acclimatized Bl6/CBA mice breathing 21% and 8% oxygen, used a nNOS inhibitor, and assessed the expression of N-methyl-d-aspartate (NMDA) glutamate receptor and nNOS (mRNA and protein). Two groups of Bl6/CBA mice (n = 60) were exposed during 2 wk either to hypoxia [barometric pressure (PB) = 420 mmHg] or normoxia (PB = 760 mmHg). At the end of exposure the medulla was removed to measure the concentration of nitric oxide (NO) metabolites, the expression of NMDA-NR1 receptor, and nNOS by real-time RT-PCR and Western blot. We also measured the ventilatory response [fraction of inspired O(2) (Fi(O(2))) = 0.21 and 0.08] before and after S-methyl-l-thiocitrulline treatment (SMTC, nNOS inhibitor, 10 mg/kg ip). Chronic hypoxia caused an increase in ventilation that was reduced after SMTC treatment mainly through a decrease in tidal volume (Vt) in normoxia and in acute hypoxia. However, the difference observed in the magnitude of acute hypoxic ventilatory response [minute ventilation (Ve) 8% - Ve 21%] in acclimatized mice was not different. Acclimatization to hypoxia induced a rise in NMDA receptor as well as in nNOS and NO production. In conclusion, our study provides evidence that activation of nNOS is involved in the ventilatory acclimatization to hypoxia in mice but not in the hypoxic ventilatory response (HVR) while the increased expression of NMDA receptor expression in the medulla of chronically hypoxic mice plays a role in acute HVR. These results are therefore consistent with central nervous system plasticity, partially involved in ventilatory acclimatization to hypoxia through nNOS.

Time course of ventilatory acclimatisation to hypoxia in a model of anemic transgenic mice.

We questioned the assumption that polycythemia is essential for adaptation to chronic hypoxia. Thus, the objective of our study was to determine if anemic Epo-TAg(h) mice could survive in hypoxia despite low oxygen carrying capacity. We explored the possibility that ventilatory acclimatisation is involved in the strategy used by anemic transgenic mice to adapt to chronic hypoxia. Epo-TAg(h) and Wild Type mice were exposed during 2 weeks at a barometric pressure of 450 Torr. After 1, 5 and 14 days of exposure, ventilation at different inspired oxygen fraction was measured in both groups. Ventilation during acclimatisation to hypoxia was significantly greater in Epo-TAg(h) than in Wild Type. The difference was mainly due to a higher tidal volume that could explain a higher arterial PO2 in Epo-TAg(h) mice. Epo-Tag(h) mice did not develop right ventricle hypertrophy after 2 weeks of exposure to hypoxia while Wild Type did. Hemoglobin concentration was 60% lower in anemic mice versus Wild Type after acclimatisation. In conclusion, ventilatory acclimatisation contributed to the adaptation of Epo-Tag(h) mice in chronic hypoxia despite low arterial oxygen carrying capacity.

Characterisation of the ventilatory response to hypoxia in a model of transgenic anemic mice.

Both polycythemia and the increase in hypoxic ventilatory response (HVR) are considered as important factors of acclimatization to hypoxia. The objective of this study was to characterise the ventilation pattern at different inspired oxygen fraction in a model of chronic anemic mice. These mice have a targeted disruption in the 5' untranslated region of the Epo gene that reduces Epo expression such that the homozygous animal is severely anemic. Ventilation in normoxia in Epo-TAg(h) mice was significantly greater than in wild type, and the difference was mainly due to a higher tidal volume. HVR was higher in Epo-TAg(h) mice at every FIO2 suggesting a higher chemosensitivity. Resting oxygen consumption was maintained in anemic mice. Maximal oxygen consumption was 30% lower while hemoglobin was 60% lower in anemic mice compared to wild type. This small decrease in maximal oxygen consumption is probably due a greater cardiac output and/or a better tissue oxygen extraction and would allow these anemic mice to acclimatize to hypoxia in spite of low oxygen carrying capacity. In conclusion, Epo-TAg(h) anemic mice showed increased ventilation and hypoxic ventilatory response. However, whether these adaptations will contribute to acclimatization in chronic hypoxia remains to be determined.

Effects of exercise and training in hypoxia on antioxidant/pro-oxidant balance.

OBJECTIVE: The aim was to investigate the effects of acute exercise under hypoxic condition and the repetition of such exercise in a 'living low-training high' training on the antioxidant/prooxidant balance. DESIGN: Randomized, repeated measures design. SETTING: Faculté de Médecine, Clermont-Ferrand, France. SUBJECTS: Fourteen runners were randomly divided into two groups. A 6-week endurance training protocol integrated two running sessions per week at the second ventilatory threshold into the usual training. INTERVENTION: A 6-week endurance training protocol integrated two running sessions per week at the second ventilatory threshold into the usual training. The first hypoxic group (HG, n=8) carried out these sessions under hypoxia (3000 m simulated altitude) and the second normoxic group (NG, n=6) in normoxia. In control period, the runners were submitted to two incremental cycling tests performed in normoxia and under hypoxia (simulated altitude of 3000 m). Plasma levels of advanced oxidation protein products (AOPP), malondialdehydes (MDA) and lipid oxidizability, ferric-reducing antioxidant power (FRAP), lipid-soluble antioxidants (alpha-tocopherol and beta-carotene) normalized for triacyglycerols and cholesterol were measured before and after the two incremental tests and at rest before and after training. RESULTS: No significant changes of MDA and AOPP level were observed after normoxic exercise, whereas hypoxic exercise induced a 56% rise of MDA and a 44% rise of AOPP. Plasma level of MDA and arterial oxygen hemoglobin desaturations after the acute both exercises were highly correlated (r=0.73). alpha-Tocopherol normalized for cholesterol and triacyglycerols increased only after hypoxic exercise (10-12%, P<0.01). After training, FRAP resting values (-21%, P<0.05) and alpha-tocopherol/triacyglycerols ratio (-24%, P<0.05) were diminished for HG, whereas NG values remained unchanged. CONCLUSIONS: Intense exercise and hypoxia exposure may have a cumulative effect on oxidative stress. As a consequence, the repetition of such exercise characterizing the 'living low-training high' model has weakened the antioxidant capacities of the athletes. SPONSORSHIP: International Olympic Committee and the Direction Régionale de la Jeunesse et des Sports de la Région Auvergne.

Is it more effective for highly trained swimmers to live and train at 1200 m than at 1850 m in terms of performance and haematological benefits?

OBJECTIVES: The effects of living and training have not been compared at different altitudes in well trained subjects. METHODS: Nine international swimmers lived and trained for 13 days similarly at 1200 m (T1200) and 1850 m (T1850). The two altitude training periods were separated by six weeks of sea level training. Before and after each training trip, subjects performed, at an altitude of 1200 m, an incremental exercise test to exhaustion of 5 x 200 m swims and a maximal test over 2000 m. RESULTS: There was no difference in Vo(2)max after each training trip: the before values were 58.5 (5.6) and 60.4 (6.7) ml/kg/min and the after values were 56.2 (5.2) and 57.1 (4.7) ml/kg/min for T1200 and T1850 respectively. The 2000 m performance had improved during T1200 (1476 (34) to 1448 (45) seconds) but not during T1850 (1458 (35) v 1450 (33) seconds). Mean cell volume increased during T1850 (86.6 (2.8) to 88.7 (2.9) microm(3)) but did not change during T1200 (85.6 (2.9) v 85.7 (2.9) microm(3)). The proportion of reticulocytes decreased during T1200 (15.2 (3.8)% to 10.3 (3.4)%) and increased during T1850 (9.3 (1.6)% to 11.9 (3.5)%). CONCLUSIONS: The short term effects of 13 days of training at 1200 m on swimming performance appear to be greater than the same type of training for the same length of time at 1850 m. As mean cell volume and proportion of reticulocytes only increased during training at 1850 m, the benefits of training at this altitude may be delayed and appear later on.

Specificity of VO2MAX and the ventilatory threshold in free swimming and cycle ergometry: comparison between triathletes and swimmers.

OBJECTIVES: To compare maximal heart rate (HRmax), maximal oxygen consumption (VO2MAX), and the ventilatory threshold (VT; %VO2MAX) during cycle ergometry and free swimming between swimmers and triathletes. METHODS: Nine swimmers and ten triathletes completed an incremental swimming and cycling test to exhaustion. Whole body metabolic responses were determined in each test. RESULTS: The swimmers exhibited a significantly higher VO2MAX in swimming than in cycling (58.4 (5.6) v 51.3 (5.1) ml/kg/min), whereas the opposite was found in the triathletes (53.0 (6.7) v 68.2 (6.8) ml/kg/min). HRmax was significantly different in the maximal cycling and swimming tests for the triathletes (188.6 (7.5) v 174.8 (9.0) beats/min). In the maximal swimming test, HRmax was significantly higher in the swimmers than in the triathletes (174.8 (9.0) v 184.6 (9.7) beats/min). No significant differences were found for VT measured in swimming and cycling in the triathletes and swimmers. CONCLUSION: This study confirms that the exercise testing mode affects the VO2MAX value, and that swimmers have very specific training adaptations even compared with triathletes. This may be a function of acute physiological responses combined with the specialist training status of the different athletes influencing maximal cardiac output or oxygen extraction. In contrast, the different training regimens do not seem to influence the VT, as this variable did not differ between the two testing modes in either group.

MIBG scintigraphic assessment of cardiac adrenergic activity in response to altitude hypoxia.

High altitude hypoxia induces a decrease in the cardiac chronotropic function at maximal exercise or in response to isoproterenol infusion, suggesting an alteration in the cardiac sympathetic activation. Iodine-123 metaiodobenzylguanidine [( 123I]MIBG) was used to map scintigraphically the cardiac sympathetic neuronal function in six male subjects (aged 32 +/- 7 yr) after an exposure to high altitude that created hypoxic conditions. Results obtained just after return to sea level (RSL) were compared with the normal values obtained after 2 or 3 mo of normoxia (N). A static image was created as the sum of the 16-EKG gated images recorded for 10 min in the anterior view of the chest at 20, 60, 120, and 240 min after injection. Regions of interest were located over the heart (H), lungs (L), and mediastinum (M) regions. There was a significant decrease in the H/M and the L/M ratios in RSL compared to N condition. Plasma norepinephrine concentration was elevated during the stay at altitude but not significantly different in RSL compared to N. In conclusion, cardiac [123I]MIBG uptake is reduced after an exposure to altitude hypoxia, supporting the hypothesis of an hypoxia-induced reduction of adrenergic neurotransmitter reserve in the myocardium. Furthermore, the observed significant decrease in pulmonary MIBG uptake suggests an alteration of endothelial cell function after exposure to chronic hypoxia.

Hypoxia-induced differential modulation of adenosinergic and muscarinic receptors in rat heart.

To better understand the decreased chronotropic response to catecholamines in chronic hypoxia, we compared the inhibitory pathways regulating adenylate cyclase in rats exposed for 30 days to hypobaric hypoxia (380 Torr; HX) with those in control rats (CT) by the analysis of adenosinergic A1-receptors (8-cyclopentyl-1,3-[3H]dipropylxanthine) and muscarinic M2-receptors ([3H]quinuclidinyl benzilate). A1-receptor density was decreased by 46% in sarcolemmal preparations without a change in the affinity for agonist [(R)-phenylisopropyladenosine]. M2-receptor density was increased (HX: 280 +/- 16 fmol/mg, CT: 188 +/- 15 fmol/mg; n = 7; P < 0.001) without a change in dissociation constant. Displacement of [3H]quinuclidinyl benzilate by carbachol indicated significant decreases in the dissociation constants of both superhigh- (HX: 73 +/- 19 nM, CT: 182 +/- 42 nM; P < 0.001) and high-affinity binding sites (HX: 4 +/- 1 microM, CT: 12 +/- 3 microM; P < 0.001). Our data show that chronic hypoxia leads to differential modulation of cardiac receptors with a downregulation of adenosine receptors and increases in muscarinic receptor affinity and density, which may contribute to the blunted responsiveness of the heart to catecholamines.

Peripheral chemoreflex function in hyperoxia following ventilatory acclimatization to altitude.

After a period of ventilatory acclimatization to high altitude (VAH), a degree of hyperventilation persists after relief of the hypoxic stimulus. This is likely, in part, to reflect the altered acid-base status, but it may also arise, in part, from the development during VAH of a component of carotid body (CB) activity that cannot be entirely suppressed by hyperoxia. To test this hypothesis, eight volunteers undergoing a simulated ascent of Mount Everest in a hypobaric chamber were acutely exposed to 30 min of hyperoxia at various stages of acclimatization. For the second 10 min of this exposure, the subjects were given an infusion of the CB inhibitor, dopamine (3 microg. kg(-1). min(-1)). Although there was both a significant rise in ventilation (P < 0.001) and a fall in end-tidal PCO(2) (P < 0.001) with VAH, there was no progressive effect of dopamine infusion on these variables with VAH. These results do not support a role for CB in generating the persistent hyperventilation that remains in hyperoxia after VAH.

Increasing maximal heart rate increases maximal O2 uptake in rats acclimatized to simulated altitude.

Maximal exercise heart rate (HRmax) is reduced after acclimatization to hypobaric hypoxia. The low HRmax contributes to reduce maximal cardiac output (Qmax) and may limit maximal O2 uptake (VO2max). The objective of these experiments was to test the hypothesis that the reduction in Qmax after acclimatization to hypoxia, due, in part, to the low HRmax, limits VO2max. If this hypothesis is correct, an increase in Qmax would result in a proportionate increase in VO2max. Rats acclimatized to hypobaric hypoxia [inspired PO2 (PIO2) = 69.8 +/- 3 Torr for 3 wk] exercised on a treadmill in hypoxic (PIO2 = 71.7 +/- 1.1 Torr) or normoxic conditions (PIO2 = 142.1 +/- 1.1 Torr). Each rat ran twice: in one bout the rat was allowed to reach its spontaneous HRmax, which was 505 +/- 7 and 501 +/- 5 beats/min in hypoxic and normoxic exercise, respectively; in the other exercise bout, HRmax was increased by 20% to the preacclimatization value of 600 beats/min by atrial pacing. This resulted in an approximately 10% increase in Qmax, since the increase in HRmax was offset by a 10% decrease in stroke volume, probably due to shortening of diastolic filling time. The increase in Qmax was accompanied by a proportionate increase in maximal rate of convective O2 delivery (Qmax x arterial O2 content), maximal work rate, and VO2max in hypoxic and normoxic exercise. The data show that increasing HRmax to preacclimatization levels increases VO2max, supporting the hypothesis that the low HRmax tends to limit VO2max after acclimatization to hypoxia.

Hypoxia-induced downregulation of beta-adrenergic receptors in rat heart.

To test the desensitization hypothesis of cardiac beta-adrenergic receptors (beta-AR) in chronic hypoxia, the effect of 1, 3, 7, 15, and 21 days of exposure to hypobaric hypoxia (380 Torr) was evaluated in Wistar rats. Exposure to hypoxia for 1-15 days did not induce any change in right and left ventricular beta-AR density (Bmax) determined with [125I]iodocyanopindolol or in antagonist affinity. After 21 days, Bmax decreased by 24% in the left ventricle. In contrast, no change in beta-AR was shown in the right hypertrophied ventricle. Agonist affinity in the left ventricle was not altered, as shown by the analysis of displacement curves of isoproterenol (normoxia 185 +/- 26 nM, hypoxia 170 +/- 11 nM). Moreover, there was no significant decrease in adenylate cyclase activity (pmol.mg-1.min-1) in the left ventricle. In the right ventricle, a 21-day exposure to hypoxia led to a decrease in basal and maximal activity when stimulated by isoproterenol. A decrease in tissue norepinephrine content was observed after 7 days of hypoxia. In conclusion, these data support the beta-AR downregulation hypothesis as one of the mechanisms of myocardial adaptation to high altitude occurring after 2-3 wk of exposure to hypoxia. The regulation pathways of beta-AR may differ between left nonhypertrophied and right hypertrophied ventricles. No evidence of profound abnormality of signal transduction was shown.

Water balance and acute mountain sickness before and after arrival at high altitude of 4,350 m.

The present study is a first attempt to measure water balance and its components at altitude by using labeled water and bromide dilution and relating the results with acute mountain sickness (AMS). Water intake, total water output, and water output in urine and feces were measured over a 4-day interval before and a subsequent 4-day interval after transport to 4,350 m. Total body water and extracellular water were measured at the start and at the end of the two intervals. There was a close relationship between energy intake and water intake, and the relationship was unchanged by the altitude intervention. Subjects developing AMS reduced energy intake and water intake cor respondingly. The increase in total body water (TBW) in subjects developing AMS was accompanied by a reduction in total water loss. They did not show the increased urine output, compensating for the reduced evaporative water loss at altitude. Subjects showed a significant increase in TBW after 4 days at altitude. Subjects with AMS showed the biggest shifts in extracellular water relative to TBW. In conclusion, fluid retention in relation to AMS is independent of a change in water requirements due to altitude exposure. Subjects developing AMS were those showing a fluid shift of at least 1 liter from the intracellular to the extracellular compartment or from the extracellular to the intracellular compartment.

Exercise training alters the effect of chronic hypoxia on myocardial adrenergic and muscarinic receptor number.

Chronic hypoxic exposure results in elevated sympathetic activity leading to downregulation of myocardial alpha(1)- and beta-adrenoceptors (alpha(1)-AR, beta-AR). On the other hand, it has been shown that sympathetic activity is reduced by exercise training. The objective of this study was to determine whether exercise training could modify the changes in receptor expression associated with acclimatization. Four groups of rats were studied: normoxic sedentary rats (NS), rats living and training in normoxia (NTN), sedentary rats living in hypoxia (HS, inspired PO(2) = 110 Torr), and rats living and training in hypoxia (HTH, inspired PO(2) = 110 Torr). Training consisted of running in a treadmill at 80% of maximal O(2) uptake during 10 wk. Myocardial receptor density was measured by radioactive ligand binding. Right ventricular (RV) hypertrophy occurred in HS but not in HTH. No effect of exercise was detected in RV weight of normoxic rats. Acclimatization to hypoxia (HS vs. NS) resulted in a decrease in both alpha(1)- and beta-AR density, whereas muscarinic receptor (M-Ach) expression increased. Hypoxic exercise training (HS vs. HTH) moderated beta-AR downregulation and M-Ach upregulation and prevented the fall in alpha(1)-AR density. Normoxic training (NS vs. NTN) did not change beta-AR density. On the other hand, densities of alpha(1)-AR in both ventricles as well as RV M-Ach increased in NTN vs. NS. The data show that exercise training in hypoxia 1) prevents RV hypertrophy, 2) suppresses the downregulation of alpha(1)-AR in the left ventricle (LV) and RV, and 3) attenuates the changes in both beta-AR and M-Ach receptor density in LV and RV. Exercise training in normoxia increases M-Ach receptor expression in the RV.