Systemic hypoxia and vasoconstrictor responsiveness in exercising human muscle.

Exercise blunts sympathetic alpha-adrenergic vasoconstriction (functional sympatholysis). We hypothesized that sympatholysis would be augmented during hypoxic exercise compared with exercise alone. Fourteen subjects were monitored with ECG and pulse oximetry. Brachial artery and antecubital vein catheters were placed in the nondominant (exercising) arm. Subjects breathed hypoxic gas to titrate arterial O2 saturation to 80% while remaining normocapnic via a rebreath system. Baseline and two 8-min bouts of rhythmic forearm exercise (10 and 20% of maximum) were performed during normoxia and hypoxia. Forearm blood flow, blood pressure, heart rate, minute ventilation, and end-tidal CO2 were measured at rest and during exercise. Vasoconstrictor responsiveness was determined by responses to intra-arterial tyramine during the final 3 min of rest and each exercise bout. Heart rate was higher during hypoxia (P < 0.01), whereas blood pressure was similar (P = 0.84). Hypoxic exercise potentiated minute ventilation compared with normoxic exercise (P < 0.01). Forearm blood flow was higher during hypoxia compared with normoxia at rest (85 +/- 9 vs. 66 +/- 7 ml/min), at 10% exercise (276 +/- 33 vs. 217 +/- 27 ml/min), and at 20% exercise (464 +/- 32 vs. 386 +/- 28 ml/min; P < 0.01). Arterial epinephrine was higher during hypoxia (P < 0.01); however, venoarterial norepinephrine difference was similar between hypoxia and normoxia before (P = 0.47) and during tyramine administration (P = 0.14). Vasoconstriction to tyramine (%decrease from pretyramine values) was blunted in a dose-dependent manner with increasing exercise intensity (P < 0.01). Interestingly, vasoconstrictor responsiveness tended to be greater (P = 0.06) at rest (-37 +/- 6% vs. -33 +/- 6%), at 10% exercise (-27 +/- 5 vs. -22 +/- 4%), and at 20% exercise (-22 +/- 5 vs. -14 +/- 4%) between hypoxia and normoxia, respectively. Thus sympatholysis is not augmented by moderate hypoxia nor does it contribute to the increased blood flow during hypoxic exercise.     

Ventilatory flow relative to intrabuccal and intraopercular volumes in the serrasalmid fish Piaractus mesopotamicus during normoxia and exposed to graded hypoxia

Ventilation volume Vg - mlH2O.min-1 ), respiratory frequency (fR - breaths.min-1) and tidal volume (VT - mlH2O.breath-1 ) were measured in a group of Piaractus mesopotamicus (650.4 +/- 204.7 g; n = 10) during normoxia and in response to graded hypoxia. The fR was maintained constant, around 100 breaths.min-1, from normoxia until the O2 tension of the inspired water (PiO2) of 53 mmHg, below which it increased progressively, reaching maximum values (157.6 +/- 6.3 breaths.min-1) at 10 mmHg. The VT rose from 1.8 +/- 0.1 to 6.0 +/- 0.5 and 5.7 +/- 0.4 mlH2O. breath-1 in the PiO2 of 16 and 10 mmHg, respectively. The Vg increased from 169.3 11.0 (normoxia) to 940.1 +/- 85.6 mlH2O. min-1 at the PiO2 of 16 mmHg, below which it also tended to decrease. A second group of fish (29 to 1510.0 g, n = 34) was used for the evaluation of allometric relationships concerning ventilation and dimensions of the buccal and opercular cavities. At maximum Vg, the VT corresponded to 93.2 +/- 2.4% of the buccal volume and 94.9 2.3% of the opercular volume, suggesting that the Vg of P. mesopotamicus is limited by the volumes of buccal and opercular cavities in severe hypoxia.     

Influence of arterial O2 on the susceptibility to posthyperventilation apnea during sleep.

To investigate the contribution of the peripheral chemoreceptors to the susceptibility to posthyperventilation apnea, we evaluated the time course and magnitude of hypocapnia required to produce apnea at different levels of peripheral chemoreceptor activation produced by exposure to three levels of inspired P(O2). We measured the apneic threshold and the apnea latency in nine normal sleeping subjects in response to augmented breaths during normoxia (room air), hypoxia (arterial O2 saturation = 78-80%), and hyperoxia (inspired O2 fraction = 50-52%). Pressure support mechanical ventilation in the assist mode was employed to introduce a single or multiple numbers of consecutive, sigh-like breaths to cause apnea. The apnea latency was measured from the end inspiration of the first augmented breath to the onset of apnea. It was 12.2 +/- 1.1 s during normoxia, which was similar to the lung-to-ear circulation delay of 11.7 s in these subjects. Hypoxia shortened the apnea latency (6.3 +/- 0.8 s; P < 0.05), whereas hyperoxia prolonged it (71.5 +/- 13.8 s; P < 0.01). The apneic threshold end-tidal P(CO2) (Pet(CO2)) was defined as the Pet(CO2)) at the onset of apnea. During hypoxia, the apneic threshold Pet(CO2) was higher (38.9 +/- 1.7 Torr; P < 0.01) compared with normoxia (35.8 +/- 1.1; Torr); during hyperoxia, it was lower (33.0 +/- 0.8 Torr; P < 0.05). Furthermore, the difference between the eupneic Pet(CO2) and apneic threshold Pet(CO2) was smaller during hypoxia (3.0 +/- 1.0 Torr P < 001) and greater during hyperoxia (10.6 +/- 0.8 Torr; P < 0.05) compared with normoxia (8.0 +/- 0.6 Torr). Correspondingly, the hypocapnic ventilatory response to CO2 below the eupneic Pet(CO2) was increased by hypoxia (3.44 +/- 0.63 l.min(-1).Torr(-1); P < 0.05) and decreased by hyperoxia (0.63 +/- 0.04 l.min(-1).Torr(-1); P < 0.05) compared with normoxia (0.79 +/- 0.05 l.min(-1).Torr(-1)). These findings indicate that posthyperventilation apnea is initiated by the peripheral chemoreceptors and that the varying susceptibility to apnea during hypoxia vs. hyperoxia is influenced by the relative activity of these receptors.     

Shivering and cardiorespiratory responses during normocapnic hypoxia in the pigeon

To study the inhibitory effect of hypoxia on the cold defense mechanism, pigeons were exposed at low ambient temperature (5 degrees C) to various inhaled gas mixtures: normoxia [0.21 fractional concentration of O2 (FIO2)], hypoxia (0.07 FIO2), and normocapnic hypoxia (0.07 FIO2 + 0.045 FICO2). Electromyographic (EMG) activity indicative of shivering thermogenesis was inhibited during hypoxia, and body temperature (Tre) fell by 0.09 degrees C/min. Respiratory frequency (f) and minute ventilation (VE) increased by 143 and 135%, respectively, compared with normoxia, but tidal volume (VT) was not changed. PO2, PCO2, and O2 contents in the arterial and mixed venous blood were decreased and pH was enhanced. During normocapnic hypoxia, shivering EMG was present at approximately 50% of the normoxic intensity; Tre fell by only 0.04 degrees C/min. Arterial and mixed venous PCO2 and pH were the same as during normoxia, but VE increased by 430% because of twofold increases in both f and VT. During normocapnic hypoxia, arterial PO2 and O2 content were higher than during hypoxia alone. We conclude that the persistence of shivering during normocapnic hypoxia is due to maintenance of critical levels of arterial PO2 and O2 content.     

Metabolic and cardiorespiratory responses of summer flounder Paralichthys dentatus to hypoxia at two temperatures

To quantify the tolerance of summer flounder Paralichthys dentatus to episodic hypoxia, resting metabolic rate, oxygen extraction, gill ventilation and heart rate were measured during acute progressive hypoxia at the fish's acclimation temperature (22° C) and after an acute temperature increase (to 30° C). Mean ±s.e. critical oxygen levels (i.e. the oxygen levels below which fish could not maintain aerobic metabolism) increased significantly from 27 ± 2% saturation (2·0 ± 0·1 mg O(2) l(-1) ) at 22° C to 39 ± 2% saturation (2·4 ± 0·1 mg O(2) l(-1) ) at 30° C. Gill ventilation and oxygen extraction changed immediately with the onset of hypoxia at both temperatures. The fractional increase in gill ventilation (from normoxia to the lowest oxygen level tested) was much larger at 22° C (6·4-fold) than at 30° C (2·7-fold). In contrast, the fractional decrease in oxygen extraction (from normoxia to the lowest oxygen levels tested) was similar at 22° C (1·7-fold) and 30° C (1·5-fold), and clearly smaller than the fractional changes in gill ventilation. In contrast to the almost immediate effects of hypoxia on respiration, bradycardia was not observed until 20 and 30% oxygen saturation at 22 and 30° C, respectively. Bradycardia was, therefore, not observed until below critical oxygen levels. The critical oxygen levels at both temperatures were near or immediately below the accepted 2·3 mg O(2) l(-1) hypoxia threshold for survival, but the increase in the critical oxygen level at 30° C suggests a lower tolerance to hypoxia after an acute increase in temperature.     

Time course of muscular blood metabolites during forearm rhythmic exercise in hypoxia

O2 concentration, PO2, PCO2, pH, osmolarity, lactate (LA), and hemoglobin (Hb) concentrations in deep forearm venous blood were repeatedly measured during submaximal exercise of forearm muscles. Concentrations of arterial blood gases were determined at rest and during exercise. Experiments were conducted under normoxia and hypobaric hypoxia (PB = 465 Torr). In arterial blood, data obtained during exercise were the same as those obtained during rest under either normoxia or hypoxia. In venous muscular blood, PO2 and O2 concentration were lower at rest and during exercise in hypoxia. The muscular arteriovenous O2 difference during exercise in hypoxia was increased by no more than 10% compared with normoxia, which implied that muscular blood flow during exercise also increased by the same percentage, if we assume that exercise O2 consumption was not affected by hypoxia. Despite increased [LA], the magnitude of changes in PCO2 and pH in hypoxia were smaller than in normoxia during exercise and recovery; this finding is probably due to the increased blood buffer value induced by the greater amount of reduced Hb in hypoxia. Hence all the changes occurring in hypoxia showed that local metabolism was less affected than we expected from the decrease in arterial PO2. The rise in [Hb] that occurred during exercise was lower in hypoxia. Possible underlying mechanisms of the [Hb] rise during exercise are discussed.     

Hypoxia potentiates exercise-induced sympathetic neural activation in humans.

Our purpose was to test the hypothesis that hypoxia potentiates exercise-induced sympathetic neural activation in humans. In 15 young (20-30 yr) healthy subjects, lower leg muscle sympathetic nerve activity (MSNA, peroneal nerve; microneurography), venous plasma norepinephrine (PNE) concentrations, heart rate, and arterial blood pressure were measured at rest and in response to rhythmic handgrip exercise performed during normoxia or isocapnic hypoxia (inspired O2 concn of 10%). Study I (n = 7): Brief (3-4 min) hypoxia at rest did not alter MSNA, PNE, or arterial pressure but did induce tachycardia [17 +/- 3 (SE) beats/min; P less than 0.05]. During exercise at 50% of maximum, the increases in MSNA (346 +/- 81 vs. 207 +/- 14% of control), PNE (175 +/- 25 vs. 120 +/- 11% of control), and heart rate (36 +/- 2 vs. 20 +/- 2 beats/min) were greater during hypoxia than during normoxia (P less than 0.05), whereas the arterial pressure response was not different (26 +/- 4 vs. 25 +/- 4 mmHg). The increase in MSNA during hypoxic exercise also was greater than the simple sum of the separate responses to hypoxia and normoxic exercise (P less than 0.05). Study II (n = 8): In contrast to study I, during 2 min of exercise (30% max) performed under conditions of circulatory arrest and 2 min of postexercise circulatory arrest (local ischemia), the MSNA and PNE responses were similar during systemic hypoxia and normoxia. Arm ischemia without exercise had no influence on any variable during hypoxia or normoxia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventilatory response to moderate and severe hypoxia in adult dogs: role of endorphins

To determine the role of opioids in modulating the ventilatory response to moderate or severe hypoxia, we studied ventilation in six chronically instrumented awake adult dogs during hypoxia before and after naloxone administration. Parenteral naloxone (200 micrograms/kg) significantly increased instantaneous minute ventilation (VT/TT) during severe hypoxia, (inspired O2 fraction = 0.07, arterial PO2 = 28-35 Torr); however, consistent effects during moderate hypoxia (inspired O2 fraction = 0.12, arterial PO2 = 40-47 Torr) could not be demonstrated. Parenteral naloxone increased O2 consumption (VO2) in severe hypoxia as well. Despite significant increases in ventilation post-naloxone during severe hypoxia, arterial blood gas tensions remained the same. Control studies revealed that neither saline nor naloxone produced a respiratory effect during normoxia; also the preservative vehicle of naloxone induced no change in ventilation during severe hypoxia. These data suggest that, in adult dogs, endorphins are released and act to restrain ventilation during severe hypoxia; the relationship between endorphin release and moderate hypoxia is less consistent. The observed increase in ventilation post-naloxone during severe hypoxia is accompanied by an increase in metabolic rate, explaining the isocapnic response.     

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)     

Evidence of sustained forearm vasodilatation after brief isocapnic hypoxia.

Healthy subjects exposed to 20 min of hypoxia increase ventilation and muscle sympathetic nerve activity (MSNA). After return to normoxia, although ventilation returns to baseline, MSNA remains elevated for up to an hour. Because forearm vascular resistance is not elevated after hypoxic exposure, we speculated that the increased MSNA might be a compensatory response to sustained release of endogenous vasodilators. We studied the effect of isocapnic hypoxia (mean arterial oxygen saturation 81.6 +/- 4.1%, end-tidal Pco2 44.7 +/- 6.3 Torr) on plethysmographic forearm blood flow (FBF) in eight healthy volunteers while infusing intra-arterial phentolamine to block local alpha-receptors. The dominant arm served as control. Forearm arterial vascular resistance (FVR) was calculated as the mean arterial pressure (MAP)-to-FBF ratio. MAP, heart rate (HR), and FVR were reported at 5-min intervals at baseline, then while infusing phentolamine during room air, isocapnic hypoxia, and recovery. Despite increases in HR during hypoxia, there was no change in MAP throughout the study. By design, FVR decreased during phentolamine infusion. Hypoxia further decreased FVR in both forearms. With continued phentolamine infusion, FVR after termination of the exposure (17.47 +/- 6.3 mmHg x min x ml(-1) x 100 ml of tissue) remained lower than preexposure baseline value (23.05 +/- 8.51 mmHg x min x ml(-1) x 100 ml of tissue; P < 0.05). We conclude that, unmasked by phentolamine, the vasodilation occurring during hypoxia persists for at least 30 min after the stimulus. This vasodilation may contribute to the sustained MSNA rise observed after hypoxia.     

Brain glutamate metabolism during hypoxia and peripheral chemodenervation

Glutamate stimulates resting ventilation by altering neural excitability centrally. Hypoxia increases central ventilatory drive through peripheral chemoreceptor stimulation and may also alter cerebral perfusion and glutamate metabolism locally. Therefore the effect of hypoxia and peripheral chemodenervation on cerebrospinal fluid (CSF) transfer rate of in vivo tracer amidated central nervous system glutamate was studied in intact and chemodenervated pentobarbital-anesthetized dogs during normoxia and after 1 h of hypoxia induced with 10 or 12% O2 in N2 breathing at constant expired ventilation and arterial CO2 tension. Chemodenervation was performed by bilateral sectioning of the carotid body nerves and cervical vagi. CSF transfer rates of radiotracer 13NH4+ and [13N]glutamine synthesized via the reaction, glutamate + NH4(+)----glutamine, in brain glia were measured during normoxia and after 1 h of hypoxia. At normoxia, maximal glial glutamine efflux rate jm = 103.3 +/- 11.2 (SE) mumol.l-1.min-1 in all animals. After 1 h of hypoxia in intact animals, jm = 78.4 +/- 10.0 mumol.l-1.min-1. In denervated animals, jm was decreased to 46.3 +/- 4.3 mumol.l-1.min-1. During hypoxia, mean cerebral cortical glutamate concentration was higher in denervated animals (9.98 +/- 1.43 mumol/g brain tissue) than in intact animals (7.63 +/- 1.82 mumol/g brain tissue) and corresponding medullary glutamate concentration tended to be higher in denervated animals. There were no differences between mean glutamine and gamma-aminobutyric acid concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventilation-perfusion inequality during normoxic and hypoxic exercise in the emu.

Many avian species exhibit an extraordinary ability to exercise under hypoxic condition compared with mammals, and more efficient pulmonary O(2) transport has been hypothesized to contribute to this avian advantage. We studied six emus (Dromaius novaehollandaie, 4-6 mo old, 25-40 kg) at rest and during treadmill exercise in normoxia and hypoxia (inspired O(2) fraction approximately 0.13). The multiple inert gas elimination technique was used to measure ventilation-perfusion (V/Q) distribution of the lung and calculate cardiac output and parabronchial ventilation. In both normoxia and hypoxia, exercise increased arterial Po(2) and decreased arterial Pco(2), reflecting hyperventilation, whereas pH remained unchanged. The V/Q distribution was unimodal, with a log standard deviation of perfusion distribution = 0.60 +/- 0.06 at rest; this did not change significantly with either exercise or hypoxia. Intrapulmonary shunt was <1% of the cardiac output in all conditions. CO(2) elimination was enhanced by hypoxia and exercise, but O(2) exchange was not affected by exercise in normoxia or hypoxia. The stability of V/Q matching under conditions of hypoxia and exercise may be advantageous for birds flying at altitude.     

Cerebral oxygen availability by NIR spectroscopy during transient hypoxia in humans

The effects of mild hypoxia on brain oxyhemoglobin, cytochrome a,a3 redox status, and cerebral blood volume were studied using near-infrared spectroscopy in eight healthy volunteers. Incremental hypoxia reaching 70% arterial O2 saturation was produced in normocapnia [end-tidal PCO2 (PETCO2) 36.9 +/- 2.6 to 34.9 +/- 3.4 Torr] or hypocapnia (PETCO2 32.8 +/- 0.6 to 23.7 +/- 0.6 Torr) by an 8-min rebreathing technique and regulation of inspired CO2. Normocapnic hypoxia was characterized by progressive reductions in arterial PO2 (PaO2, 89.1 +/- 3.5 to 34.1 +/- 0.1 Torr) with stable PETCO2, arterial PCO2 (PaCO2), and arterial pH and resulted in increases in heart rate (35%) systolic blood pressure (14%), and minute ventilation (5-fold). Hypocapnic hypoxia resulted in progressively decreasing PaO2 (100.2 +/- 3.6 to 28.9 +/- 0.1 Torr), with progressive reduction in PaCO2 (39.0 +/- 1.6 to 27.3 +/- 1.9 Torr), and an increase in arterial pH (7.41 +/- 0.02 to 7.53 +/- 0.03), heart rate (61%), and ventilation (3-fold). In the brain, hypoxia resulted in a steady decline of cerebral oxyhemoglobin content and a decrease in oxidized cytochrome a,a3. Significantly greater loss of oxidized cytochrome a,a3 occurred for a given decrease in oxyhemoglobin during hypocapnic hypoxia relative to normocapnic hypoxia. Total blood volume response during hypoxia also was significantly attenuated by hypocapnia, because the increase in volume was only half that of normocapnic subjects. We conclude that cytochrome a,a3 oxidation level in vivo decreases at mild levels of hypoxia. PaCO is an important determinant of brain oxygenation, because it modulates ventilatory, cardiovascular, and cerebral O2 delivery responses to hypoxia.     

Sustained isocapnic hypoxia suppresses the perception of the magnitude of inspiratory resistive loads.

The sensation of increased respiratory resistance or effort is likely to be important for the initiation of alerting or arousal responses, particularly in sleep. Hypoxia, through its central nervous system-depressant effects, may decrease the perceived magnitude of respiratory loads. To examine this, we measured the effect of isocapnic hypoxia on the ability of 10 normal, awake males (mean age = 24.0 +/- 1.8 yr) to magnitude-scale five externally applied inspiratory resistive loads (mean values from 7.5 to 54.4 cmH(2)O. l(-1). s). Each subject scaled the loads during 37 min of isocapnic hypoxia (inspired O(2) fraction = 0.09, arterial O(2) saturation of approximately 80%) and during 37 min of normoxia, using the method of open magnitude numerical scaling. Results were normalized by modulus equalization to allow between-subject comparisons. With the use of peak inspiratory pressure (PIP) as the measure of load stimulus magnitude, the perception of load magnitude (Psi) increased linearly with load and, averaged for all loaded breaths, was significantly lower during hypoxia than during normoxia (20.1 +/- 0.9 and 23.9 +/- 1.3 arbitrary units, respectively; P = 0. 048). Psi declined with time during hypoxia (P = 0.007) but not during normoxia (P = 0.361). Our result is remarkable because PIP was higher at all times during hypoxia than during normoxia, and previous studies have shown that an elevation in PIP results in increased Psi. We conclude that sustained isocapnic hypoxia causes a progressive suppression of the perception of the magnitude of inspiratory resistive loads in normal subjects and could, therefore, impair alerting or arousal responses to respiratory loading.     

Inspiratory muscle work in acute hypoxia influences locomotor muscle fatigue and exercise performance of healthy humans

Our aim was to isolate the independent effects of 1) inspiratory muscle work (W(b)) and 2) arterial hypoxemia during heavy-intensity exercise in acute hypoxia on locomotor muscle fatigue. Eight cyclists exercised to exhaustion in hypoxia [inspired O(2) fraction (Fi(O(2))) = 0.15, arterial hemoglobin saturation (Sa(O(2))) = 81 +/- 1%; 8.6 +/- 0.5 min, 273 +/- 6 W; Hypoxia-control (Ctrl)] and at the same work rate and duration in normoxia (Sa(O(2)) = 95 +/- 1%; Normoxia-Ctrl). These trials were repeated, but with a 35-80% reduction in W(b) achieved via proportional assist ventilation (PAV). Quadriceps twitch force was assessed via magnetic femoral nerve stimulation before and 2 min after exercise. The isolated effects of W(b) in hypoxia on quadriceps fatigue, independent of reductions in Sa(O(2)), were revealed by comparing Hypoxia-Ctrl and Hypoxia-PAV at equal levels of Sa(O(2)) (P = 0.10). Immediately after hypoxic exercise potentiated twitch force of the quadriceps (Q(tw,pot)) decreased by 30 +/- 3% below preexercise baseline, and this reduction was attenuated by about one-third after PAV exercise (21 +/- 4%; P = 0.0007). This effect of W(b) on quadriceps fatigue occurred at exercise work rates during which, in normoxia, reducing W(b) had no significant effect on fatigue. The isolated effects of reduced Sa(O(2)) on quadriceps fatigue, independent of changes in W(b), were revealed by comparing Hypoxia-PAV and Normoxia-PAV at equal levels of W(b). Q(tw,pot) decreased by 15 +/- 2% below preexercise baseline after Normoxia-PAV, and this reduction was exacerbated by about one-third after Hypoxia-PAV (-22 +/- 3%; P = 0.034). We conclude that both arterial hypoxemia and W(b) contribute significantly to the rate of development of locomotor muscle fatigue during exercise in acute hypoxia; this occurs at work rates during which, in normoxia, W(b) has no effect on peripheral fatigue.     

Ventilatory acclimatization to hypoxia is not dependent on arterial hypoxemia

Goats were prepared so that one carotid body (CB) could be perfused with blood in which the gas tensions could be controlled independently from the blood perfusing the systemic arterial system, including the brain. Since one CB is functionally adequate, the nonperfused CB was excised. To determine whether systemic arterial hypoxemia is necessary for ventilatory acclimatization to hypoxia (VAH), the CB was perfused with hypoxic normocapnic blood for 6 h [means +/- SE: partial pressure of carotid body O2 (PcbO2), 40.6 +/- 0.3 Torr; partial pressure of carotid body CO2 (PcbCO2), 38.8 +/- 0.2 Torr] while the awake goat breathed room air to maintain systemic arterial normoxia. In control periods before and after CB hypoxia the CB was perfused with hyperoxic normocapnic blood. Changes in arterial PCO2 (PaCO2) were used as an index of changes in ventilation. Acute hypoxia (0.5 h of hypoxic perfusion) resulted in hyperventilation sufficient to reduce average PaCO2 by 6.7 Torr from control (P less than 0.05). Over the subsequent 5.5 h of hypoxic perfusion, average PaCO2 decreased further, reaching 4.8 Torr below that observed acutely (P less than 0.05). Acute CB hyperoxic perfusion (20 min) following 6 h of hypoxia resulted in only partial restoration of PaCO2 toward control values; PaCO2 remained 7.9 Torr below control (P less than 0.05). The progressive hyperventilation that occurred during and after 6 h of CB hypoxia with concomitant systemic normoxia is similar to that occurring with total body hypoxia. We conclude that systemic (and probably brain) hypoxia is not a necessary requisite for VAH.     

Oxygen transport to exercising leg in chronic hypoxia

Residence at high altitude could be accompanied by adaptations that alter the mechanisms of O2 delivery to exercising muscle. Seven sea level resident males, aged 22 +/- 1 yr, performed moderate to near-maximal steady-state cycle exercise at sea level in normoxia [inspired PO2 (PIO2) 150 Torr] and acute hypobaric hypoxia (barometric pressure, 445 Torr; PIO2, 83 Torr), and after 18 days' residence on Pikes Peak (4,300 m) while breathing ambient air (PIO2, 86 Torr) and air similar to that at sea level (35% O2, PIO2, 144 Torr). In both hypoxia and normoxia, after acclimatization the femoral arterial-iliac venous O2 content difference, hemoglobin concentration, and arterial O2 content, were higher than before acclimatization, but the venous PO2 (PVO2) was unchanged. Thermodilution leg blood flow was lower but calculated arterial O2 delivery and leg VO2 similar in hypoxia after vs. before acclimatization. Mean arterial pressure (MAP) and total peripheral resistance in hypoxia were greater after, than before, acclimatization. We concluded that acclimatization did not increase O2 delivery but rather maintained delivery via increased arterial oxygenation and decreased leg blood flow. The maintenance of PVO2 and the higher MAP after acclimatization suggested matching of O2 delivery to tissue O2 demands, with vasoconstriction possibly contributing to the decreased flow.     

Effect of hypoxia on arterial and venous blood levels of oxygen, carbon dioxide, hydrogen ions and lactate during incremental forearm exercise

The purpose of the present study was to investigate whether, in humans, hypoxia results in an elevated lactate production from exercising skeletal muscle. Under conditions of both hypoxia [inspired oxygen fraction (F1O2): 11.10%] and normoxia (F1O2: 20.94%), incremental exercise of a forearm was performed. The exercise intensity was increased every minute by 1.6 kg.m.min-1 until exhaustion. During the incremental exercise the partial pressure of oxygen (PO2) and carbon dioxide (PCO2), oxygen saturation (SO2), pH and lactate concentration [HLa] of five subjects, were measured repeatedly in blood from the brachial artery and deep veins from muscles in the forearm of both the active and inactive sides. The hypoxia (arterial SO2 approximately 70%) resulted in (1) the difference in [HLa] in venous blood from active muscle (values during exercise-resting value) often being more than twice that for normoxia, (2) a significantly greater difference in venous-arterial (v-a) [HLa] for the exercising muscle compared to normoxia, and (3) a difference in v-a [HLa] for non-exercising muscle that was slightly negative during normoxia and more so with hypoxia. These studies suggest that lower O2 availability to the exercising muscle results in increased lactate production.     

Effects of temperature and oxygen availability on circulating catecholamines in the toad Bufo marinus.

The release of catecholamines during hypoxia has received limited attention in amphibians and the adrenergic regulation of cardio-pulmonary functions is, therefore, not well understood at the organismic level. To describe the changes in plasma catecholamine concentrations, we exposed toads (Bufo marinus) to different levels of hypoxia at two temperatures (15 and 25 degrees C). In addition, blood oxygen binding properties were determined in vitro at 15 and 25 degrees C at two different pH values. Hypoxia elicited a significant increase in plasma catecholamines (adrenaline and noradrenaline) at both temperatures, in spite of a respiratory alkalosis. At 15 degrees C, the increase was from 2.6+/-1.0 in normoxia to 4.8+/-1.4 ng ml(-1) at an inspired oxygen fraction of 0.05. At 25 degrees C, the hypoxic release of catecholamines was significantly higher (maximum levels of 44.8+/-11.6 ng ml(-1)). Plasma noradrenaline concentration was elevated at the most severe hypoxic levels, suggestive of an adrenal release. The arterial oxygen threshold for catecholamine release were approximately 1.0 mmol O(2) l(-1) blood or a PaO(2) of 30 mmHg. The P(50) values at 15 degrees C were 23.5+/-0.7 and 28.9+/-1.0 mmHg at pH 7.98+/-0.01 and 7.62+/-0.02, respectively, and increased to 36.5+/-0.6 and 43.0+/-1.1 mmHg at pH 8.04+/-0.04 and 7.67+/-0.05, respectively, at 25 degrees C. The oxygen equilibrium curves were linear when transformed to Hill-plots and Hills n (the haemoglobin subunit co-operativity) ranged between 2.24 and 2.75. The in vitro blood O(2) binding properties corresponded well with in vivo data.     

Anaerobic energy provision does not limit Wingate exercise performance in endurance-trained cyclists.

The aim of this study was to evaluate the effects of severe acute hypoxia on exercise performance and metabolism during 30-s Wingate tests. Five endurance- (E) and five sprint- (S) trained track cyclists from the Spanish National Team performed 30-s Wingate tests in normoxia and hypoxia (inspired O(2) fraction = 0.10). Oxygen deficit was estimated from submaximal cycling economy tests by use of a nonlinear model. E cyclists showed higher maximal O(2) uptake than S (72 +/- 1 and 62 +/- 2 ml x kg(-1) x min(-1), P < 0.05). S cyclists achieved higher peak and mean power output, and 33% larger oxygen deficit than E (P < 0.05). During the Wingate test in normoxia, S relied more on anaerobic energy sources than E (P < 0.05); however, S showed a larger fatigue index in both conditions (P < 0.05). Compared with normoxia, hypoxia lowered O(2) uptake by 16% in E and S (P < 0.05). Peak power output, fatigue index, and exercise femoral vein blood lactate concentration were not altered by hypoxia in any group. Endurance cyclists, unlike S, maintained their mean power output in hypoxia by increasing their anaerobic energy production, as shown by 7% greater oxygen deficit and 11% higher postexercise lactate concentration. In conclusion, performance during 30-s Wingate tests in severe acute hypoxia is maintained or barely reduced owing to the enhancement of the anaerobic energy release. The effect of severe acute hypoxia on supramaximal exercise performance depends on training background.