Chloride cell responses to ion challenge in two tropical freshwater fish,the erythrinids Hoplias malabaricus and Hoplerythrinus unitaeniatus

Chloride cell (CC) responses to ion challenge and plasma ion concentration were evaluated in two ecologically distinct erythrinids, Hoplias malabaricus, an exclusively water-breathing species, and Hoplerythrinus unitaeniatus, a facultative air-breathing fish, at one, two, seven, and 15 days of exposure to deionized water and to ion-rich water. H. malabaricus displayed high CC proliferation on filament and lamellar epithelium during exposure to deionized water and significant CC proliferation in the filament epithelium on the first day of exposure to water rich in NaCl and Ca2+ and in the lamellar epithelium on the first, second, and seventh day of exposure to such water. CC proliferation in H. unitaeniatus occurred only in the lamellar epithelium of fish exposed to deionized water. CC proliferation on both species was not accompanied by significant increase of CC density in contact with the external medium. The increase in the CC fractional area (CCFA) resulted from the increase of individual CC apical surface area on the first and second days of exposure to deionized water in H. malabaricus and only on the first day in H. unitaeniatus. Plasma ions in both erythrinid species showed transitory changes and, on the fifteenth day of exposure to the two types of experimental water, the plasma ion concentration was similar to the control fish. The CC responses of these erythrinid fish showed that CC proliferation depends on previous CC density in the gill and is not related solely to exposure to ion-poor water. Furthermore, CC proliferation in gill epithelium did not always involve an increase of CC density in contact with the external medium.     

Adenosine A2A-receptor blockade abolishes the roll-off respiratory response to hypoxia in awake lambs

Adenosine (ADO) receptor antagonists (aminophylline, caffeine) blunt the respiratory roll-off response to hypoxia in the newborn. This study was designed to determine the ADO receptor subtype involved in the respiratory depression. Chronically catheterized lambs of 7-16 days of age breathed via face mask a gas mixture with a fraction of inspired O2 of 0.21 (normoxia) or 0.07 (hypoxia), while being infused intravascularly with 9-cyclopentyl-1,3-dipropylxanthine (DPCPX; ADO A1-receptor antagonist, n=8), ZM-241385 (ADO A2A-receptor antagonist, n=7), or vehicle. Ventilation was measured at 20 degrees C by a turbine transducer flowmeter. In normoxia [arterial Po2 (PaO2) of approximately 83 Torr], infusion of vehicle did not alter cardiorespiratory measurements, whereas hypoxia (PaO2 of approximately 31 Torr, 15 min) elicited biphasic effects on mean arterial pressure (transient increase), heart rate (HR; diminishing tachycardia), and minute ventilation. In the latter, hypoxia increased ventilation to a peak value of approximately 2.5 times control within the first 3 min, which was followed by a significant (P<0.05) decline to approximately 50% of the maximum increment over the subsequent 7 min. ZM-241385 abolished the hypoxic ventilatory roll-off and blunted the rate of rise in HR without affecting mean arterial pressure or rectal temperature responses. In normoxia, DPCPX increased ventilation and mean arterial pressure but did not change HR. Compared with vehicle, DPCPX did not significantly affect cardiorespiratory responses to hypoxemia (PaO2 of approximately 31 Torr, 10 min). It is concluded that 1) ADO A2A receptors are critically involved in the ventilatory roll-off and HR responses to hypoxia, and 2) ADO A1 receptors, which are tonically active in cardiorespiratory control in normoxia, appear to have little impact on hypoxic ventilatory depression.     

Ventilatory effects and interactions with change in PaO2 in awake goats.

We utilized selective carotid body (CB) perfusion while changing inspired O2 fraction in arterial isocapnia to characterize the non-CB chemoreceptor ventilatory response to changes in arterial PO2 (PaO2) in awake goats and to define the effect of varying levels of CB PO2 on this response. Systemic hyperoxia (PaO2 greater than 400 Torr) significantly increased inspired ventilation (VI) and tidal volume (VT) in goats during CB normoxia, and systemic hypoxia (PaO2 = 29 Torr) significantly increased VI and respiratory frequency in these goats. CB hypoxia (CB PO2 = 34 Torr) in systemic normoxia significantly increased VI, VT, and VT/TI; the ventilatory effects of CB hypoxia were not significantly altered by varying systemic PaO2. We conclude that ventilation is stimulated by systemic hypoxia and hyperoxia in CB normoxia and that this ventilatory response to changes in systemic O2 affects the CB O2 response in an additive manner.     

MK-801 alters diaphragmatic activities in unanesthetized rats differently between normoxia and hypoxia

This study was designed to examine how systemic administration of an N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, altered respiratory timing in unanesthetized rats under normoxia and hypoxia. To detect fine changes in inspiratory time (TI) and expiratory time (TE), and cycle duration (TTOT), we prepared a diaphragmatic electromyogram (EMGdia). Diaphragm electrodes and arterial and venous catheters were inserted into Wistar rats (n = 8) under pentobarbital anesthesia. The next day, EMGdia was recorded before and after intravenous administration of MK-801 (3 mg/kg) under normoxia and hypoxia (12% O2) without anesthesia, and the respiratory timing (TI, TE, TTOT), respiratory frequency (fR), and amplitude of the integrated EMGdia were measured. Arterial blood gases (ABGs), mean arterial pressure (MAP), and heart rate (fH) were also measured with the EMGdia. Under normoxia, MK-801 increased fR owing to a significant decrease in TE, and elevated both MAP and fH. Under hypoxia, MK-801 suppressed an increase in fR owing to a significant increase in TI, and did not accelerate fH. In both gaseous conditions, on ABGs, MK-801 did not alter partial pressure of O2 (PaO2) or CO2 (PaCO2), and slightly decreased pH (but not less than 7.4). MK-801 significantly decreased hypoxic response (%change from normoxia) in fR, and increased that in EMGdia amplitude, and did not alter a total ventilatory index (fRxEMGdia amplitude). The results suggest that an NMDA receptor-mediated mechanism partially determines fR through significant alterations in respiratory timing, particularly in which the hypoxic ventilatory response was obtained in unanesthetized rats.     

Ventilation and metabolism in a large semifossorial marsupial: the effect of graded hypoxia and hypercapnia

Metabolic and ventilatory variables were measured in a large semifossorial marsupial, the hairy-nosed wombat (Lasiorhinus latifrons, 21.9 kg). In normoxia, the rate of oxygen consumption was 63% of that predicted for a similar-sized marsupial, and the level of ventilation (V(E)) was such that the convective requirement (V(E)/VO2) was similar to other mammals. Exposure to hypercapnia (5% CO(2)) evoked a hyperventilatory response (3.55 x normoxia) that was no different to that observed for epigeal (surface-dwelling) marsupials; the increase in V(E) was primarily achieved with an increase in tidal volume. Exposure to hypoxia (15% to 8% O(2)) resulted in a hyperventilation (principally through an increase in frequency), although the response was blunted (in 8% O(2), 1.85 x normoxia) and only at the severest levels did hypometabolism contribute. The attenuated response to hypoxia in the wombat is presumably a reflection of a semifossorial lifestyle and a tolerance to this respiratory stimulant.     

Effects of thermal stress on respiratory responses to hypoxia of a South American Prochilodontid fish, Prochilodus scrofa

Oxygen consumption (o₂) and respiratory variables were measured in the Prochilodontid fish, Prochilodus scrofa exposed to graded hypoxia after changes in temperature. The measurements were performed on fish acclimated to 25°C and in four further groups also acclimated to 25°C and then changed to 15, 20, 30 and 35°C. An increase in o₂ occurred with rising temperature, but at each temperature o₂ was kept constant over a wide range of O₂ tensions of inspired water ( Pi o₂). The critical oxygen tensions ( Pc o₂) were Pi o₂= 22 mmHg for 25°C acclimated specimens and after transfer from 25°C to 15, 20, 30 and 35°C the Pc o₂ changed to Pi o₂= 28, 22, 24 and 45 mmHg, respectively. Gill ventilation ( _G ) increased or decreased following the changes in o₂ as the temperature changed and was the result of an accentuated increase in breath frequency. During hypoxia the increases in _G were characterized by larger increases in breath volume. Oxygen extraction was kept almost constant at about 63% regardless of temperature and ambient oxygen tensions in normoxia and moderate hypoxia ( P o₂∼70 mmHg). P. scrofa showed high tolerance to hypoxia after abrupt changes in temperature although its survival upon transfer to 35°C could become limited by the capacity of ventilatory mechanisms to alleviate hypoxic stress.     

Cod (Gadus morhua) cardiorespiratory physiology and hypoxia tolerance following acclimation to low-oxygen conditions

Previous research has shown that hypoxia-acclimated Atlantic cod (Gadus morhua) have significantly reduced cardiac function but can consume more oxygen for a given cardiac output (Q). However, it is not known (1) which physiological changes permit a greater "oxygen pulse" (oxygen consumed per mL of blood pumped) in hypoxia-acclimated individuals or (2) whether chronic exposure to low-oxygen conditions improves the hypoxia tolerance of cod. Thus, we exposed normoxia- and hypoxia-acclimated (> 6 wk at a water oxygen partial pressure [P(w)O(2)] ~8-9 kPa) cod to a graded normoxia challenge until loss of equilibrium occurred while recording the following cardiorespiratory variables: oxygen consumption (MO(2)), ventilatory rate, cardiac function (Q, heart rate f(H), and stroke volume S(V)), ventral aortic blood pressure (P(VA)), venous oxygen partial pressure (P(v)O(2)) and oxygen content (C(v)O(2)), plasma catecholamines, and blood hemoglobin ([Hb]) and hematocrit (Hct). In addition, we performed in vitro hemoglobin oxygen binding curves to examine whether hypoxia acclimation influences hemoglobin functional properties. Numerous physiological adjustments occurred in vivo during the > 6 wk of hypoxia acclimation: that is, increased f(H), decreased S(V) and Q, elevated [Hb], enhanced tissue oxygen extraction (by 10% at a P(w)O(2) of 20 kPa), and a more robust stress response as evidenced by circulating catecholamine levels that were two to eight times higher when fish were acutely exposed to severe hypoxia. In contrast, chronic hypoxia had no significant effect on the affinity of hemoglobin for oxygen, on in vitro hemoglobin oxygen carrying capacity, or on the cod's hypoxia tolerance (H(crit); the P(w)O(2) at which the fish lost equilibrium, which was 4.3 ± 0.2 and 4.8 ± 0.3 kPa in normoxia- and hypoxia-acclimated fish, respectively). These data suggest that while chronic hypoxia results in numerous physiological adjustments, these changes do not improve the cod's capacity to tolerate low-oxygen conditions.     

Effects of acute hypoxia and CO2 inhalation on systemic and peripheral oxygen uptake and circulatory responses during moderate exercise

The effect of acute hypoxia and CO2 inhalation on leg blood flow (LBF), on leg vascular resistance (LVR) and on oxygen supply to and oxygen consumption in the exercising leg was studied in nine healthy male subjects during moderate one-leg exercise. Each subject exercised for 20 min on a cycle ergometer in four different conditions: normoxia, normoxia + 2% CO2, hypoxia corresponding to an altitude of 4000 m above sea level, and hypoxia + 1.2% CO2. Gas exchange, heart rate (HR), arterial blood pressure, and LBF were measured, and arterial and venous blood samples were analysed for PCO2, PO2, oxygen saturation, haematocrit and haemoglobin concentration. Systemic oxygen consumption was 1.83 l.min-1 (1.48-2.59) and was not affected by hypoxia or CO2 inhalation in hypoxia. HR was unaffected by CO2, but increased from 136 beat.min-1 (111-141) in normoxia to 155 (139-169) in hypoxia. LBF was 6.5 l.min-1 (5.4-7.6) in normoxia and increased significantly in hypoxia to 8.4 (5.9-10.1). LVR decreased significantly from 2.23 kPa.l-1.min (1.89-2.99) in normoxia to 1.89 (1.53-2.52) in hypoxia. The increase in LBF from normoxia to hypoxia correlated significantly with the decrease in LVR. When CO2 was added in hypoxia a significant correlation was also found between the decrease in LBF and the increase in LVR. In normoxia, the addition of CO2 caused a significant increase in mean blood pressure. Oxygen consumption in the exercising leg (leg VO2) in normoxia was 0.97 l.min-1 (0.72-1.10), and was unaffected by hypoxia and CO2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory responses of the air-breathing fish Hoplosternum littorale to hypoxia and hydrogen sulfide

The present study analyzes the respiratory responses of the neotropical air-breathing fish Hoplosternum littorale to graded hypoxia and increased sulfide concentrations. The oxygen uptake (VO2), critical O2 tension (PcO2), respiratory (fR) and air-breathing (fRA) frequencies in response to graded hypoxia were determined for fish acclimated to 28 degrees C. H. littorale was able to maintain a constant VO2 down to a PcO2 of 50 mm Hg, below which fish became dependent on the environmental O2 even with significant increases in fR. The fRA was kept constant around 1 breath h(-1) above 50 mm Hg and increased significantly below 40 mm Hg, reaching maximum values (about 4.5 breaths h(-1)) at 10 mm Hg. The lethality to sulfide concentrations under normoxic and hypoxic conditions were also determined along with the fRA. For the normoxic fish the sulfide lethal limit was about 70 microM, while in the hypoxic ones this limit increased to 87 muM. The high sulfide tolerance of H. littorale may be attributed to the air-breathing capability, which is stimulated by this compound.     

Exercise training in normobaric hypoxia in endurance runners. I. Improvement in aerobic performance capacity.

This study investigates whether a 6-wk intermittent hypoxia training (IHT), designed to avoid reductions in training loads and intensities, improves the endurance performance capacity of competitive distance runners. Eighteen athletes were randomly assigned to train in normoxia [Nor group; n = 9; maximal oxygen uptake (VO2 max) = 61.5 +/- 1.1 ml x kg(-1) x min(-1)] or intermittently in hypoxia (Hyp group; n = 9; VO2 max = 64.2 +/- 1.2 ml x kg(-1) x min(-1)). Into their usual normoxic training schedule, athletes included two weekly high-intensity (second ventilatory threshold) and moderate-duration (24-40 min) training sessions, performed either in normoxia [inspired O2 fraction (FiO2) = 20.9%] or in normobaric hypoxia (FiO2) = 14.5%). Before and after training, all athletes realized 1) a normoxic and hypoxic incremental test to determine VO2 max and ventilatory thresholds (first and second ventilatory threshold), and 2) an all-out test at the pretraining minimal velocity eliciting VO2 max to determine their time to exhaustion (T(lim)) and the parameters of O2 uptake (VO2) kinetics. Only the Hyp group significantly improved VO2 max (+5% at both FiO2, P < 0.05), without changes in blood O2-carrying capacity. Moreover, T(lim) lengthened in the Hyp group only (+35%, P < 0.001), without significant modifications of VO2 kinetics. Despite similar training load, the Nor group displayed no such improvements, with unchanged VO2 max (+1%, nonsignificant), T(lim) (+10%, nonsignificant), and VO2 kinetics. In addition, T(lim) improvements in the Hyp group were not correlated with concomitant modifications of other parameters, including VO2 max or VO2 kinetics. The present IHT model, involving specific high-intensity and moderate-duration hypoxic sessions, may potentialize the metabolic stimuli of training in already trained athletes and elicit peripheral muscle adaptations, resulting in increased endurance performance capacity.     

Circulation and respiratory control in millimetre-sized animals (Daphnia magna, Folsomia candida ) studied by optical methods

During hypoxia, oxyregulating water-breathers usually control O₂ uptake by changing ventilatory convection. Using optical techniques we studied ventilation, circulation and respiratory control in small animals, a millimetre in size, which were more or less pronounced oxyregulators (Daphnia magna, Folsomia candida). In Daphnia we found no adaptive changes in the ventilatory water flow rate during hypoxia. Frequency and amplitude of the movements of the thoracic limbs remained constant during this environmental condition. During anoxia there was a reduction in both. In contrast to ventilatory convection, the circulatory blood flow rate adapted to hypoxia. At low oxygen partial pressures, the heart frequency strongly increased (compensatory tachycardia) in Daphnia, whereas the stroke volume remained constant. Accordingly, there was an increase in cardiac output during hypoxia. Folsomia also showed a marked increase of heart frequency during severe hypoxia. The adaptive changes in blood flow rate should help to maintain sufficient partial pressure differences between medium, blood and tissues and should help to avoid anoxic zones in the animal. During anoxia, the heart continued to beat in Daphnia (at a rate more or less similar to normoxia, but with a reduced stroke volume) for periods of many hours. The heart frequency showed typical courses during anoxia and subsequent normoxia, which are probably related to energy metabolism. Accepted: 28 February 1997     

Ventilatory and metabolic responses to cold and hypoxia in intact and carotid body-denervated rats.

The effects of hypoxia on thermoregulation and ventilatory control were studied in conscious rats before and after carotid denervation (CD). Measurements of metabolic rate (VO2), ventilation (V), shivering intensity (SI), and colonic temperature (Tc) were made in groups of eight rats subjected to three protocols. In protocols 1 and 2, at ambient temperature (Ta) of 25 and 5 degrees C, respectively, rats were exposed to normoxia and hypoxia [inspired O2 fraction (FIO2) 0.13-0.11]. In protocol 3, Ta was decreased from 25 to 5 degrees C in 30-min steps of 5 degrees C. Recordings were made in normoxia and hypoxia (FIO2 0.12). The results show that in both intact and CD rats 1) in normoxia, cold exposure increased VO2, V, and SI, and these increases were proportional to the decrease in Ta; 2) hypoxia induced only a transient decrease in SI, and, for a given Ta, VO2 was reduced whereas V and SI were increased; and 3) in CD rats, V increased less during cold exposure in both normoxia and hypoxia; VO2 and Tc were more depressed during hypoxia. It is concluded that 1) the interaction between Ta and FIO2 in the control of V is partly dependent on the carotid body afferents, 2) shivering thermogenesis may be transiently affected by hypoxia independently of the carotid body afferents, and 3) nonshivering thermogenesis may be directly inhibited by hypoxia, especially during cold exposure.     

Determinants of maximal oxygen uptake in severe acute hypoxia

To unravel the mechanisms by which maximal oxygen uptake (VO2 max) is reduced with severe acute hypoxia in humans, nine Danish lowlanders performed incremental cycle ergometer exercise to exhaustion, while breathing room air (normoxia) or 10.5% O2 in N2 (hypoxia, approximately 5,300 m above sea level). With hypoxia, exercise PaO2 dropped to 31-34 mmHg and arterial O2 content (CaO2) was reduced by 35% (P < 0.001). Forty-one percent of the reduction in CaO2 was explained by the lower inspired O2 pressure (PiO2) in hypoxia, whereas the rest was due to the impairment of the pulmonary gas exchange, as reflected by the higher alveolar-arterial O2 difference in hypoxia (P < 0.05). Hypoxia caused a 47% decrease in VO2 max (a greater fall than accountable by reduced CaO2). Peak cardiac output decreased by 17% (P < 0.01), due to equal reductions in both peak heart rate and stroke VOlume (P < 0.05). Peak leg blood flow was also lower (by 22%, P < 0.01). Consequently, systemic and leg O2 delivery were reduced by 43 and 47%, respectively, with hypoxia (P < 0.001) correlating closely with VO2 max (r = 0.98, P < 0.001). Therefore, three main mechanisms account for the reduction of VO2 max in severe acute hypoxia: 1) reduction of PiO2, 2) impairment of pulmonary gas exchange, and 3) reduction of maximal cardiac output and peak leg blood flow, each explaining about one-third of the loss in VO2 max.     

Effects of acute hypobaric hypoxia on the appearance of ingested deuterium from a deuterium oxide-labelled carbohydrate beverage in body fluids of humans during prolonged cycling exercise

To determine whether or not acute hypobaric hypoxia alters the rate of water absorption from a carbohydrate beverage ingested during exercise, six men cycled for 80 min on three randomly assigned different occasions. In one trial, exercise was performed in hypoxia (barometric pressure, P(B) = 594 hPa, altitude 4,400 m) at an exercise intensity selected to elicit 75% of the individual's maximal oxygen uptake (VO2max) previously determined in such conditions. In the two other experiments, the subjects cycled in normoxia (P(B) = 992 hPa) at the same absolute and the same relative intensities as in hypoxia, which corresponded to 55% and 75%, respectively, of their VO2max determined in normoxia. The subjects consumed 400 ml of a 12.5% glucose beverage just prior to exercise, and 250 ml of the same drink at 20, 40 and 60 min from the beginning of exercise. The first drink contained 20 ml of deuterium oxide to serve as a tracer for the entry of water into body fluids. The heart rate (HR) during exercise was higher in hypoxia than in normoxia at the same absolute exercise intensity, whereas it was similar to HR measured in normoxia at the same relative exercise intensity. Both in normoxia and hypoxia, plasma noradrenaline concentrations were related to the relative exercise intensity up to 40 min of exercise. Beyond that duration, when exercise was performed at the highest absolute power in normoxia, the noradrenaline response was higher than in hypoxia at the same relative exercise intensity. No significant differences were observed among experimental conditions, either in temporal profiles of plasma D accumulation or in elimination of water ingested in sweat. Conversely, elimination in urine of the water ingested appeared to be related to the severity of exercise, either high absolute power or the same relative power combined with hypoxia. We concluded that water absorption into blood after drinking a 12.5% glucose beverage is not altered during cycling exercise in acute hypobaric hypoxia. It is suggested that the elimination of water ingested in sweat and urine may be dependent on local circulatory adjustments during exercise.     

The ergogenic effect of recombinant human erythropoietin on VO2max depends on the severity of arterial hypoxemia

Treatment with recombinant human erythropoietin (rhEpo) induces a rise in blood oxygen-carrying capacity (CaO(2)) that unequivocally enhances maximal oxygen uptake (VO(2)max) during exercise in normoxia, but not when exercise is carried out in severe acute hypoxia. This implies that there should be a threshold altitude at which VO(2)max is less dependent on CaO(2). To ascertain which are the mechanisms explaining the interactions between hypoxia, CaO(2) and VO(2)max we measured systemic and leg O(2) transport and utilization during incremental exercise to exhaustion in normoxia and with different degrees of acute hypoxia in eight rhEpo-treated subjects. Following prolonged rhEpo treatment, the gain in systemic VO(2)max observed in normoxia (6-7%) persisted during mild hypoxia (8% at inspired O(2) fraction (F(I)O(2)) of 0.173) and was even larger during moderate hypoxia (14-17% at F(I)O(2) = 0.153-0.134). When hypoxia was further augmented to F(I)O(2) = 0.115, there was no rhEpo-induced enhancement of systemic VO(2)max or peak leg VO(2). The mechanism highlighted by our data is that besides its strong influence on CaO(2), rhEpo was found to enhance leg VO(2)max in normoxia through a preferential redistribution of cardiac output toward the exercising legs, whereas this advantageous effect disappeared during severe hypoxia, leaving augmented CaO(2) alone insufficient for improving peak leg O(2) delivery and VO(2). Finally, that VO(2)max was largely dependent on CaO(2) during moderate hypoxia but became abruptly CaO(2)-independent by slightly increasing the severity of hypoxia could be an indirect evidence of the appearance of central fatigue.     

Oxygen uptake, acid-base status, and performance with varied inspired oxygen fractions

Six subjects rode a bicycle ergometer on three occasions breathing 17, 21, or 60% oxygen. In addition to rest and recovery periods, each subject worked for 10 min at 55% of maximal oxygen uptake (VO2 max) and then to exhaustion at approximately 90% VO2 max. Performance time, inspired and expired gas fractions, ventilation, and arterialized venous oxygen tension (PO2), carbon dioxide tension (PCO2), lactate, and pH were measured. VO2, carbon dioxide output, [H+]a, and [HCO3-]a were calculated. Performance times were longer in hyperoxia than in normoxia or hypoxia. However, VO2 was not different at exhaustion in normoxia compared with hypoxia or hyperoxia. During exercise, hypoxia was associated with increased lactate levels and decreased [H+]a, PCO2, and [HCO3-]a. The opposite trends were generally associated with hyperoxia. At exhaustion, [H+]a was not different under any inspired oxygen fraction. These results support the contention that oxygen is not limiting for exercise of this intensity and duration. The results also suggest that [H+] is a possible limiting factor and that the effect of oxygen on performance is perhaps related to control of [H+].     

Performance of runners and swimmers after four weeks of intermittent hypobaric hypoxic exposure plus sea level training.

This double-blind, randomized, placebo-controlled trial examined the effects of 4 wk of resting exposure to intermittent hypobaric hypoxia (IHE, 3 h/day, 5 days/wk at 4,000-5,500 m) or normoxia combined with training at sea level on performance and maximal oxygen transport in athletes. Twenty-three trained swimmers and runners completed duplicate baseline time trials (100/400-m swims, or 3-km run) and measures for maximal oxygen uptake (VO(2max)), ventilation (VE(max)), and heart rate (HR(max)) and the oxygen uptake at the ventilatory threshold (VO(2) at VT) during incremental treadmill or swimming flume tests. Subjects were matched for sex, sport, performance, and training status and divided randomly between hypobaric hypoxia (Hypo, n = 11) and normobaric normoxia (Norm, n = 12) groups. All tests were repeated within the first (Post1) and third weeks (Post2) after the intervention. Time-trial performance did not improve in either group. We could not detect a significant difference between groups for a change in VO(2max), VE(max), HR(max), or VO(2) at VT after the intervention (group x test interaction P = 0.31, 0.24, 0.26, and 0.12, respectively). When runners and swimmers were considered separately, Hypo swimmers appeared to increase VO(2max) (+6.2%, interaction P = 0.07) at Post2 following a precompetition taper and increased VO(2) at VT (+8.9 and +12.1%, interaction P = 0.007 and 0.006, at Post1 and Post2). We conclude that this "dose" of IHE was not sufficient to improve performance or oxygen transport in this heterogeneous group of athletes. Whether there are potential benefits of this regimen for specific sports or training/tapering strategies may require further study.     

Exercise-induced hypoxaemia in highly trained cyclists at 40% peak oxygen uptake

A group of 15 competitive male cyclists [mean peak oxygen uptake, VO2peak 68.5 (SEM 1.5 ml x kg(-1) x min(-1))] exercised on a cycle ergometer in a protocol which began at an intensity of 150 W and was increased by 25 W every 2 min until the subject was exhausted. Blood samples were taken from the radial artery at the end of each exercise intensity to determine the partial pressures of blood gases and oxyhaemoglobin saturation (SaO2), with all values corrected for rectal temperature. The SaO2 was also monitored continuously by ear oximetry. A significant decrease in the partial pressure of oxygen in arterial blood (PaO2) was seen at the first exercise intensity (150 W, about 40% VO2peak). A further significant decrease in PaO2 occurred at 200 W, whereafter it remained stable but still significantly below the values at rest, with the lowest value being measured at 350 W [87.0 (SEM 1.9) mmHg]. The partial pressure of carbon dioxide in arterial blood (PaCO2) was unchanged up to an exercise intensity of 250 W whereafter it exhibited a significant downward trend to reach its lowest value at an exercise intensity of 375 W [34.5 (SEM 0.5) mmHg]. During both the first (150 W) and final exercise intensities (VO2peak) PaO2 was correlated significantly with both partial pressure of oxygen in alveolar gas (P(A)O2, r = 0.81 and r = 0.70, respectively) and alveolar-arterial difference in oxygen partial pressure (P(A-a)O2, r = 0.63 and r = 0.86, respectively) but not with PaCO2. At VO2peak PaO2 was significantly correlated with the ventilatory equivalents for both oxygen uptake and carbon dioxide output (r = 0.58 and r = 0.53, respectively). When both P(A)O2 and P(A-a)O2 were combined in a multiple linear regression model, at least 95% of the variance in PaO2 could be explained at both 150 W and VO2peak. A significant downward trend in SaO2 was seen with increasing exercise intensity with the lowest value at 375 W [94.6 (SEM 0.3)%]. Oximetry estimates of SaO2 were significantly higher than blood measurements at all times throughout exercise and no significant decrease from rest was seen until 350 W. The significant correlations between PaO2 and P(A)O2 with the first exercise intensity and at VO2peak led to the conclusion that inadequate hyperventilation is a major contributor to exercise-induced hypoxaemia.     

Peripheral chemoreflex responsiveness is increased at elevated levels of carbon dioxide after episodic hypoxia in awake humans.

We hypothesized that the acute ventilatory response to hypoxia is enhanced after exposure to episodic hypoxia in awake humans. Eleven subjects completed a series of rebreathing trials before and after exposure to eight 4-min episodes of hypoxia. During the rebreathing trials, subjects initially hyperventilated to reduce the partial pressure of carbon dioxide (Pet(CO(2))) below 25 Torr. Subjects then breathed from a bag containing normocapnic (42 Torr), low (50 Torr), or high oxygen (140 Torr) gas mixtures. During the trials, Pet(CO(2)) increased while a constant oxygen level was maintained. The point at which ventilation began to rise in a linear fashion as Pet(CO(2)) increased was considered to be the ventilatory recruitment threshold. The ventilatory response below and above the recruitment threshold was determined. Ventilation did not persist above baseline values immediately after exposure to episodic hypoxia; however, Pet(CO(2)) levels were reduced compared with baseline. In contrast, compared with baseline, the ventilatory response to progressive increases in carbon dioxide during rebreathing trials in the presence of low but not high oxygen levels was increased after exposure to episodic hypoxia. This increase occurred when carbon dioxide levels were above but not below the ventilatory recruitment threshold. We conclude that long-term facilitation of ventilation (i.e., increases in ventilation that persist when normoxia is restored after episodic hypoxia) is not expressed in awake humans in the presence of hypocapnia. Nevertheless, despite this lack of expression, the acute ventilatory response to hypoxia in the presence of hypercapnia is increased after exposure to episodic hypoxia.     

Hypoxic depression of circadian rhythms in adult rats.

Because the circadian rhythms of oxygen consumption (VO(2)) and body temperature (T(b)) could be contributed to by differences in thermogenesis and because hypoxia depresses thermogenesis in its various forms, we tested the hypothesis that hypoxia blunts the normal daily oscillations in VO(2) and T(b). Adult rats were instrumented for measurements of T(b) and activity by telemetry; VO(2) was measured by an open-flow method. Animals were exposed to normoxia (21% O(2)), hypoxia (10.5% O(2)), and normoxia again, each 1 wk in duration, in either a 12:12-h light-dark cycle ("synchronized") or constant light ("free running"). In this latter case, the period of the cycle was approximately 25 h. In synchronized conditions, hypoxia almost eliminated the T(b) circadian oscillation, because of the blunting of the T(b) rise during the dark phase. On return to normoxia, T(b) rapidly increased toward the maximum normoxic values, and the normal cycle was then reestablished. In hypoxia, the amplitude of the activity and VO(2) oscillations averaged, respectively, 37 and 56% of normoxia. In free-running conditions, on return to normoxia the rhythm was reestablished at the expected phase of the cycle. Hence, the action of hypoxia was not on the clock itself but probably at the hypothalamic centers of thermoregulation. Hyperoxia (40% O(2)) or hypercapnia (3% CO(2)) had no significant effects on circadian oscillations, indicating that the effects of hypoxia did not reflect an undifferentiated response to changes in environmental gases. Modifications of the metabolism and T(b) rhythms during hypoxia could be at the origin of sleep disturbances in cardiorespiratory patients and at high altitude.