Augmented hypoxic ventilatory response in men at altitude.

To test the hypothesis that the hypoxic ventilatory response (HVR) of an individual is a constant unaffected by acclimatization, isocapnic 5-min step HVR, as delta VI/delta SaO2 (l.min-1.%-1, where VI is inspired ventilation and SaO2 is arterial O2 saturation), was tested in six normal males at sea level (SL), after 1-5 days at 3,810-m altitude (AL1-3), and three times over 1 wk after altitude exposure (PAL1-3). Equal medullary central ventilatory drive was sought at both altitudes by testing HVR after greater than 15 min of hyperoxia to eliminate possible ambient hypoxic ventilatory depression (HVD), choosing for isocapnia a P'CO2 (end tidal) elevated sufficiently to drive hyperoxic VI to 140 ml.kg-1.min-1. Mean P'CO2 was 45.4 +/- 1.7 Torr at SL and 33.3 +/- 1.8 Torr on AL3, compared with the respective resting control end-tidal PCO2 of 42.3 +/- 2.0 and 30.8 +/- 2.6 Torr. SL HVR of 0.91 +/- 0.38 was unchanged on AL1 (30 +/- 18 h) at 1.04 +/- 0.37 but rose (P less than 0.05) to 1.27 +/- 0.57 on AL2 (3.2 +/- 0.8 days) and 1.46 +/- 0.59 on AL3 (4.8 +/- 0.4 days) and remained high on PAL1 at 1.44 +/- 0.54 and PAL2 at 1.37 +/- 0.78 but not on PAL3 (days 4-7). HVR was independent of test SaO2 (range 60-90%). Hyperoxic HCVR (CO2 response) was increased on AL3 and PAL1. Arterial pH at congruent to 65% SaO2 was 7.378 +/- 0.019 at SL, 7.44 +/- 0.018 on AL2, and 7.412 +/- 0.023 on AL3.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determinants of endurance in well-trained cyclists

Fourteen competitive cyclists who possessed a similar maximum O2 consumption (VO2 max; range, 4.6-5.0 l/min) were compared regarding blood lactate responses, glycogen usage, and endurance during submaximal exercise. Seven subjects reached their blood lactate threshold (LT) during exercise of a relatively low intensity (group L) (i.e., 65.8 +/- 1.7% VO2 max), whereas exercise of a relatively high intensity was required to elicit LT in the other seven men (group H) (i.e., 81.5 +/- 1.8% VO2 max; P less than 0.001). Time to fatigue during exercise at 88% of VO2 max was more than twofold longer in group H compared with group L (60.8 +/- 3.1 vs. 29.1 +/- 5.0 min; P less than 0.001). Over 92% of the variance in performance was related to the % VO2 max at LT and muscle capillary density. The vastus lateralis muscle of group L was stressed more than that of group H during submaximal cycling (i.e., 79% VO2 max), as reflected by more than a twofold greater (P less than 0.001) rate of glycogen utilization and blood lactate concentration. The quality of the vastus lateralis in groups H and L was similar regarding mitochondrial enzyme activity, whereas group H possessed a greater percentage of type I muscle fibers (66.7 +/- 5.2 vs. 46.9 +/- 3.8; P less than 0.01). The differing metabolic responses to submaximal exercise observed between the two groups appeared to be specific to the leg extension phase of cycling, since the blood lactate responses of the two groups were comparable during uphill running. These data indicate that endurance can vary greatly among individuals with an equal VO2 max.(ABSTRACT TRUNCATED AT 250 WORDS)     

Live high-train low for 24 days increases hemoglobin mass and red cell volume in elite endurance athletes.

The effect of live high-train low on hemoglobin mass (Hbmass) and red cell volume (RCV) in elite endurance athletes is still controversial. We expected that Hb(mass) and RCV would increase, when using a presumably adequate hypoxic dose. An altitude group (AG) of 10 Swiss national team orienteers (5 men and 5 women) lived at 2,500 m (18 h per day) and trained at 1,800 and 1,000 m above sea level for 24 days. Before and after altitude, Hbmass, RCV (carbon monoxide rebreathing method), blood, iron, and performance parameters were determined. Seven Swiss national team cross-country skiers (3 men and 4 women) served as "sea level" (500-1,600 m) control group (CG) for the changes in Hbmass and RCV. The AG increased Hbmass (805+/-209 vs. 848+/-225 g; P<0.01) and RCV (2,353+/-611 vs. 2,470+/-653 ml; P<0.01), whereas there was no change for the CG (Hbmass: 849+/-197 vs. 858+/-205 g; RCV: 2,373+/-536 vs. 2,387+/-551 ml). Serum erythropoietin (P<0.001), reticulocytes (P<0.001), transferrin (P<0.001), soluble transferrin receptor (P<0.05), and hematocrit (P<0.01) increased, whereas ferritin (P<0.05) decreased in the AG. These changes were associated with an increased maximal oxygen uptake (3,515+/-837 vs. 3,660+/-770 ml/min; P<0.05) and improved 5,000-m running times (1,098+/-104 vs. 1,080+/-98 s; P<0.01) from pre- to postaltitude. Living at 2,500 m and training at lower altitudes for 24 days increases Hbmass and RCV. These changes may contribute to enhance performance of elite endurance athletes.     

Plasma trace elements levels are not altered by submaximal exercise intensities in well-trained endurance euhydrated athletes

The purpose of this study was to assess the effect of relative exercise intensity on various plasma trace elements in euhydrated endurance athletes.Twenty-seven well-trained endurance athletes performed a cycloergometer test: after a warm-up of 10 min at 2.0 W kg⁻¹, workload increased by 0.5 W kg⁻¹ every 10 min until exhaustion. Oxygen uptake, blood lactate concentration ([La⁻]_b), and plasma ions (Zn, Se, Mn and Co) were measured at rest, at the end of each stage, and 3, 5 and 7 min post-exercise. Urine specific gravity (U_SG) was measured before and after the test, and subjects drank water ad libitum. Fat oxidation (FAT_OXR), carbohydrate oxidation (CHO_OXR), energy expenditure from fat (EE_FAT), from carbohydrates (EE_CHO) and total EE (EE_T) were estimated using stoichiometric equations. A repeated measure (ANOVA) was used to compare plasma ion levels at each exercise intensity level. The significance level was set at P < 0.05.No significant differences were found in U_SG between, before, and after the test (1.014 ± 0.004 vs. 1.014 ± 0.004 g cm⁻³) or in any plasma ion level as a function of intensity. There were weak significant correlations of Zn (r = 0.332, P < 0.001) and Se (r = 0.242, P < 0.01) with [La⁻]_b, but no relationships were established between [La⁻]_b, VO₂, FAT_OXR, CHO_OXR, EE_FAT, EE_CHO, or EE_T and plasma ion levels.Acute exercise at different submaximal intensities in euhydrated well-trained endurance athletes does not provoke a change in plasma trace element levels, suggesting that plasma volume plays an important role in the homeostasis of these elements during exercise.     

Low acute hypoxic ventilatory response and hypoxic depression in acute altitude sickness

Persons with acute altitude sickness hypoventilate at high altitude compared with persons without symptoms. We hypothesized that their hypoventilation was due to low initial hypoxic ventilatory responsiveness, combined with subsequent blunting of ventilation by hypocapnia and/or prolonged hypoxia. To test this hypothesis, we compared eight subjects with histories of acute altitude sickness with four subjects who had been asymptomatic during prior altitude exposure. At a simulated altitude of 4,800 m, the eight susceptible subjects developed symptoms of altitude sickness and had lower minute ventilations and higher end-tidal PCO2's than the four asymptomatic subjects. In measurements made prior to altitude exposure, ventilatory responsiveness to acute hypoxia was reduced in symptomatic compared to asymptomatic subjects, both when measured under isocapnic and poikolocapnic (no added CO2) conditions. Diminution of the poikilocapnic relative to the isocapnic hypoxic response was similar in the two groups. Ventilation fell, and end-tidal PCO2 rose in both groups during 30 min of steady-state hypoxia relative to values observed acutely. After 4.5 h at 4,800 m, ventilation was lower than values observed acutely at the same arterial O2 saturation. The reduction in ventilation in relation to the hypoxemia present was greater in symptomatic than in asymptomatic persons. Thus the hypoventilation in symptomatic compared to asymptomatic subjects was attributable both to a lower acute hypoxic response and a subsequent greater blunting of ventilation at high altitude.     

Human hypoxic ventilatory response with blood dopamine content under intermittent hypoxic training

Adaptation to intermittent hypoxia can enhance a hypoxic ventilatory response (HVR) in healthy humans. Naturally occurring oscillations in blood dopamine (DA) level may modulate these responses. We have measured ventilatory response to hypoxia relative to blood DA concentration and its precursor DOPA before and after a 2-week course of intermittent hypoxic training (IHT). Eighteen healthy male subjects (mean 22.8+/-2.1 years old) participated in the study. HVRs to isocapnic, progressive, hypoxic rebreathing were recorded and analyzed using piecewise linear approximation. Rebreathing lasted for 5-6 min until inspired O2 reached 8 to 7%. IHT consisted of three identical daily rebreathing sessions separated by 5-min breaks for 14 consecutive days. Before and after the 2-week course of IHT, blood was sampled from the antecubital vein to measure DA and DOPA content. The investigation associated pretraining high blood DA and DOPA values with low HVR (r = -0.66 and -0.75, respectively), elevated tidal volume (r = 0.58 and 0.37) and vital capacity (r = 0.69 and 0.58), and reduced respiratory frequency (r = -0.89 and -0.82). IHT produced no significant change in ventilatory responses to mild hypoxic challenge (Peto2 from 110 to 70-80 mm Hg; 1 mm Hg = 133.3 Pa) but elicited a 96% increase in ventilatory response to severe hypoxia (from 70-80 to 45 mm Hg). Changes in HVRs were not accompanied by statistically significant shifts in blood DA content (24% change), although a twofold increase in DOPA concentration was observed. Individual subject's changes in DA and DOPA content were not correlated with HVR changes when these two parameters were evaluated in relation to the IHT. We hypothesize that DA flowing to the carotid body through the blood may provoke DA autoreceptor-mediated inhibition of endogenous DA synthesis-release, as shown in our baseline data.     

Mediation of reduced ventilatory response to exercise after endurance training

To investigate the mechanism by which ventilatory (VE) demand is modulated by endurance training, 10 normal subjects performed cycle ergometer exercise of 15 min duration at each of four constant work rates. These work rates represented 90% of the anaerobic threshold (AT) work rate and 25, 50, and 75% of the difference between maximum O2 consumption and AT work rates for that subject (as determined from previous incremental exercise tests). Subjects then underwent 8 wk of strenuous cycle ergometer exercise for 45 min/day. They then repeated the four constant work rate tests at work rates identical to those used before training. During tests before and after training, VE and gas exchange were measured breath by breath and rectal temperature (Tre) was measured continuously. A venous blood sample was drawn at the end of each test and assayed for lactate (La), epinephrine (EPI), and norepinephrine (NE). We found that the VE for below AT work was reduced minimally by training (averaging 3 l/min). For the above AT tests, however, training reduced VE markedly, by an average of 7, 23, and 37 l/min for progressively higher work rates. End-exercise La, NE, EPI, and Tre were all lower for identical work rates after training. Importantly, the magnitude of the reduction in VE was well correlated with the reduction in end-exercise La (r = 0.69) with an average decrease of 5.8 l/min of VE per milliequivalent per liter decrease in La. Correlations of VE with NE, EPI, and Tre were much less strong (r = 0.49, 0.43, and 0.15, respectively).     

"Living high-training low" altitude training improves sea level performance in male and female elite runners.

Acclimatization to moderate high altitude accompanied by training at low altitude (living high-training low) has been shown to improve sea level endurance performance in accomplished, but not elite, runners. Whether elite athletes, who may be closer to the maximal structural and functional adaptive capacity of the respiratory (i.e., oxygen transport from environment to mitochondria) system, may achieve similar performance gains is unclear. To answer this question, we studied 14 elite men and 8 elite women before and after 27 days of living at 2,500 m while performing high-intensity training at 1,250 m. The altitude sojourn began 1 wk after the USA Track and Field National Championships, when the athletes were close to their season's fitness peak. Sea level 3,000-m time trial performance was significantly improved by 1.1% (95% confidence limits 0.3-1.9%). One-third of the athletes achieved personal best times for the distance after the altitude training camp. The improvement in running performance was accompanied by a 3% improvement in maximal oxygen uptake (72.1 +/- 1.5 to 74.4 +/- 1.5 ml x kg(-1) x min(-1)). Circulating erythropoietin levels were near double initial sea level values 20 h after ascent (8.5 +/- 0.5 to 16.2 +/- 1.0 IU/ml). Soluble transferrin receptor levels were significantly elevated on the 19th day at altitude, confirming a stimulation of erythropoiesis (2.1 +/- 0.7 to 2.5 +/- 0.6 microg/ml). Hb concentration measured at sea level increased 1 g/dl over the course of the camp (13.3 +/- 0.2 to 14.3 +/- 0.2 g/dl). We conclude that 4 wk of acclimatization to moderate altitude, accompanied by high-intensity training at low altitude, improves sea level endurance performance even in elite runners. Both the mechanism and magnitude of the effect appear similar to that observed in less accomplished runners, even for athletes who may have achieved near maximal oxygen transport capacity for humans.     

Role of glutamate as the central neurotransmitter in the hypoxic ventilatory response.

Recent data suggest that the increase in ventilation during hypoxia may be related to the release of the excitatory amino acid neurotransmitter glutamate centrally. To further investigate this, we studied the effects of MK-801, a selective noncompetitive N-methyl-D-aspartate receptor antagonist, on the hypoxic ventilatory response in lightly anesthetized spontaneously breathing intact dogs. The cardiopulmonary effects of sequential ventriculocisternal perfusion (VCP) at the rate of 1 ml/min with mock cerebrospinal fluid (CSF, control) and MK-801 (2 mM) were compared during normoxia and 8 min of hypoxic challenge with 12% O2. Minute ventilation (VE), tidal volume (VT), and respiratory frequency (f) were recorded continuously, and hemodynamic parameters [heart rate (HR), blood pressure (MAP), cardiac output (CO), pulmonary arterial pressure, and pulmonary capillary wedge pressure] were measured periodically. Each dog served as its own baseline control before and after each period of sequential VCP under the two different O2 conditions. During 15 min of normoxia, there were no significant changes in the cardiopulmonary parameters with mock CSF VCP, whereas with MK-801 VCP for 15 min, VE decreased by approximately 27%, both by reductions in VT and f (17 and 9.5%, respectively). HR, MAP, and CO were unchanged. During 8 min of hypoxia with mock CSF VCP, VE increased by 171% associated with increased VT and f (25 and 125%, respectively). HR, MAP, and CO were likewise augmented. In contrast, the hypoxic response during MK-801 VCP was characterized by an increased VE of 84%, mainly by a rise in f by 83%, whereas the VT response was abolished. The cardiovascular excitation was also inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influences of gender and sex hormones on hypoxic ventilatory response in cats.

Hypoxic ventilatory response (HVR) is known to be increased by female as well as male sex hormones, but whether there are differences in HVR between men and women remains unclear. To determine whether gender differences exist in HVR, we undertook systematic comparisons of resting ventilation and HVR in awake male and female cats. Furthermore to explore the potential contribution of sex hormones to gender differences observed, we compared neutered and intact cats of both sexes. Resting ventilation differed among the four groups, but differences disappeared with correction for body weight. Intact females had a lower end-tidal PCO2 than intact male cats (females: 31.6 +/- 0.4 Torr vs. males: 33.6 +/- 0.4 Torr, P less than 0.05), indicating an increased alveolar ventilation per unit CO2 production. HVR expressed as the shape parameter A was similar among the four groups of animals. However, baseline (hyperoxic; end-tidal PO2 greater than 200 Torr) minute ventilation [VI(PO2 greater than 200)] differed among the groups. Therefore we normalized HVR by dividing the shape parameter A by VI(PO2 greater than 200) to compare the relative hypoxic chemosensitivity among the various groups of animals. In addition, we further normalized HVR for body weight, because body size influences ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Time domains of the hypoxic ventilatory response in ectothermic vertebrates

Over a decade has passed since Powell et al. (Respir Physiol 112:123–134, 1998) described and defined the time domains of the hypoxic ventilatory response (HVR) in adult mammals. These time domains, however, have yet to receive much attention in other vertebrate groups. The initial, acute HVR of fish, amphibians and reptiles serves to minimize the imbalance between oxygen supply and demand. If the hypoxia is sustained, a suite of secondary adjustments occur giving rise to a more long-term balance (acclimatization) that allows the behaviors of normal life. These secondary responses can change over time as a function of the nature of the stimulus (the pattern and intensity of the hypoxic exposure). To add to the complexity of this process, hypoxia can also lead to metabolic suppression (the hypoxic metabolic response) and the magnitude of this is also time dependent. Unlike the original review of Powell et al. (Respir Physiol 112:123–134, 1998) that only considered the HVR in adult animals, we also consider relevant developmental time points where information is available. Finally, in amphibians and reptiles with incompletely divided hearts the magnitude of the ventilatory response will be modulated by hypoxia-induced changes in intra-cardiac shunting that also improve the match between O₂ supply and demand, and these too change in a time-dependent fashion. While the current literature on this topic is reviewed here, it is noted that this area has received little attention. We attempt to redefine time domains in a more ‘holistic’ fashion that better accommodates research on ectotherms. If we are to distinguish between the genetic, developmental and environmental influences underlying the various ventilatory responses to hypoxia, however, we must design future experiments with time domains in mind.     

A low carbohydrate-protein supplement improves endurance performance in female athletes

The purpose of this study was to investigate if a low mixed carbohydrate (CHO) plus moderate protein (PRO) supplement, provided during endurance exercise, would improve time to exhaustion (TTE) in comparison to a traditional 6% CHO supplement. Fourteen (n = 14) trained female cyclists and triathletes cycled on 2 separate occasions for 3 hours at intensities varying between 45 and 70% VO2max, followed by a ride to exhaustion at an intensity approximating the individual's ventilatory threshold average 75.06% VO2max. Supplements (275 mL) were provided every 20 minutes during exercise and were composed of a CHO mixture (1% each of dextrose, fructose, and maltodextrin) + 1.2% PRO (CHO + PRO) or 6% dextrose only (CHO). The TTE was significantly greater with CHO + PRO in comparison to with CHO (49.94 ± 7.01 vs. 42.36 ± 6.21 minutes, respectively, p < 0.05). Blood glucose was significantly lower during the CHO + PRO trial (4.07 ± 0.12 mmol · L(-1)) compared to during the CHO trial (4.47 ± 0.12 mmol · L(-1)), with treatment × time interactions occurring from 118 minutes of exercise until exhaustion (p < 0.05). Results from the present study suggest that the addition of a moderate amount of PRO to a low mixed CHO supplement improves endurance performance in women above that of a traditional 6% CHO supplement. Improvement in performance occurred despite CHO + PRO containing a lower CHO and caloric content. It is likely that the greater performance seen with CHO + PRO was a result of the CHO-PRO combination and the use of a mixture of CHO sources.     

Metabolic response of endurance athletes to training with added load

Endurance athletes were divided into experimental (n = 12) and control (n = 12) groups to investigate the effects of extra-load training on energy metabolism during exercise. A vest weighing 9%-10% body weight was worn every day from morning to evening for 4 weeks including every (n = 6) or every other (n = 6) training session. After 4 weeks the control group had a lower blood lactate concentration during submaximal running, whereas the experimental group had significantly higher blood lactate and oxygen uptake (p less than 0.01--p less than 0.05), and a lower 2 mmol lactate threshold (p less than 0.05) and an increased blood lactate concentration after a short running test to exhaustion (p less than 0.05). Those experimental subjects (n = 6) who used the added load during every training session had a lower 2 mmol lactate threshold, improved running time to exhaustion, improved vertical velocity when running up stairs and an increased VO2 during submaximal running after the added load increased anaerobic metabolism in the leg muscle during submaximal and maximal exercise. An increased recruitment and adaptation of the fast twitch muscle fibres is suggested as the principal explanation for the observed changes.     

Acute lung injury augments hypoxic ventilatory response in the absence of systemic hypoxemia.

The objective of the present study was to examine the impact of early stages of lung injury on ventilatory control by hypoxia and hypercapnia. Lung injury was induced with intratracheal instillation of bleomycin (BM; 1 unit) in adult, male Sprague-Dawley rats. Control animals underwent sham surgery with saline instillation. Five days after the injections, lung injury was present in BM-treated animals as evidenced by increased neutrophils and protein levels in bronchoalveolar lavage fluid, as well as by changes in lung histology and computed tomography images. There was no evidence of pulmonary fibrosis, as indicated by lung collagen content. Basal core body temperature, arterial Po(2), and arterial Pco(2) were comparable between both groups of animals. Ventilatory responses to hypoxia (12% O(2)) and hypercapnia (7% CO(2)) were measured by whole body plethysmography in unanesthetized animals. Baseline respiratory rate and the hypoxic ventilatory response were significantly higher in BM-injected compared with control animals (P = 0.003), whereas hypercapnic ventilatory response was not statistically different. In anesthetized, spontaneously breathing animals, response to brief hyperoxia (Dejours' test, an index of peripheral chemoreceptor sensitivity) and neural hypoxic ventilatory response were augmented in BM-exposed relative to control animals, as measured by diaphragmatic electromyelograms. The enhanced hypoxic sensitivity persisted following bilateral vagotomy, but was abolished by bilateral carotid sinus nerve transection. These data demonstrate that afferent sensory input from the carotid body contributes to a selective enhancement of hypoxic ventilatory drive in early lung injury in the absence of pulmonary fibrosis and arterial hypoxemia.     

Effect of brain blood flow on hypoxic ventilatory response in humans

To assess the effect of brain blood flow on hypoxic ventilatory response, we measured arterial and internal jugular venous blood gases and ventilation simultaneously and repeatedly in eight healthy male humans in two settings: 1) progressive and subsequent sustained hypoxia, and 2) stepwise and progressive hypercapnia. Ventilatory response to progressive isocapnic hypoxia [arterial O2 partial pressure 155.9 +/- 4.0 (SE) to 46.7 +/- 1.5 Torr] was expressed as change in minute ventilation per change in arterial O2 saturation and varied from -0.16 to -1.88 [0.67 +/- 0.19 (SE)] l/min per % among subjects. In the meanwhile, jugular venous PCO2 (PjCO2) decreased significantly from 51.0 +/- 1.1 to 47.3 +/- 1.0 Torr (P less than 0.01), probably due to the increase in brain blood flow, and stayed at the same level during 15 min of sustained hypoxia. Based on the assumption that PjCO2 reflects the brain tissue PCO2, we evaluated the depressant effect of fall in PjCO2 on hypoxic ventilatory response, using a slope for ventilation-PjCO2 line which was determined in the second set of experiments. Hypoxic ventilatory response corrected with this factor was -1.31 +/- 0.33 l/min per %, indicating that this factor modulated hypoxic ventilatory response in humans. The ventilatory response to progressive isocapnic hypoxia did not correlate with this factor but significantly correlated with the withdrawal test (modified transient O2 test), which was performed on a separate day. Accordingly we conclude that an increase in brain blood flow during exposure to moderate hypoxia may substantially attenuate the ventilatory response but that it is unlikely to be the major factor of the interindividual variation of progressive isocapnic hypoxic ventilatory response in humans.