Дисертації з теми "Hypoxic exercise"

Aim The aim for this present study was to investigate the acute metabolic response from intermittent resistance exercise during hypoxia, with the following research questions: (1) Are blood levels of lactate and glucose different between hypoxia and normoxia? (2) Does hypoxia induce higher lactate accumulation and pH reduction in the human skeletal muscle? (3) Is there a relationship between plasma-, blood- and muscle lactate? Method Eight healthy males (30 ± 2 years) performed 6 sets of unilateral leg extension on each leg (75% of 1RM) with randomized normoxic (20,9% inspired 𝑂2) and normobaric hypoxic (12% inspired 𝑂2) conditions. A total of 5 muscle biopsies was extracted from m. Vastus Lateralis (pre-, post exercise, 90-, 180min and 24h post exercise) during both normoxia and hypoxia trials, separated by one week for all participants. Blood samples were repeatedly taken with 20 min intervals. Heart Rate (HR) and saturation (𝑆𝑝𝑂2) were measured by a pulsoximeter during resistance exercise. Results No significant main effect was observed for blood lactate and glucose levels as well as the muscle lactate accumulation and pH between normoxia and hypoxia. However, pH in muscle showed a trend between the conditions post exercise where hypoxia reached lower levels in total (P=0.08). Significant correlations were observed for blood- and plasma lactate, where hypoxia showed a stronger relationship than normoxia (r=0.98 compared to r=0.87). Equal findings for the correlation of muscle- and plasma lactate showed an even greater coefficient value for hypoxia compared to normoxia (r=0.860 compared to r=0.59). Conclusion Summarized data indicated that no significant difference between hypoxia and normoxia was evident. Nonetheless, tendencies illustrate that hypoxia may alter the metabolic response slightly. However, further research is needed to draw a conclusion between the conditions.
Syftet med denna studie är att undersöka kroppens akuta metabola svar från intermittent styrketräning under hypoxi, med följande frågeställningar: (1) Skiljer sig nivåerna av laktat och glukos i blodet mellan hypoxi och normoxi? (2) Skapar hypoxi större laktatansamling och pH reduktion i människoskelettmuskeln? (3) Finns det en relation mellan plasma-, blod- och muskellaktat? Metod Åtta friska män (30 ± 2 år) deltog där deltagarna utförde 6 set unilateral benextension för varje ben (75% 1RM). Intermittent styrketräning randomiserades med hypoxi som utfördes med 12% syrgas och normoxi som bibehöll normal syrgasnivå (20,9% syrgas). Under två testdagar togs 5 muskelbiopsier från m. Vastus Lateralis (före-, efter träning, 90-, 180min och 24h efter träning) på vartannat ben per testdag. Hjärtfrekvensen och 𝑆𝑝𝑂2 mättes via pulsoximeter under träningen. Resultat Ingen signifikant huvudeffekt påvisades mellan hypoxi och normoxi för blodlaktat samt glukos, såväl som laktatackumulationen och pH värdet i muskeln. Muskel pH visade en trend där hypoxi efter styrketräning nådde lägre totalnivå än normoxi (P=0,08). Vidare observerades hypoxi att ha starka relationer mellan blod- och plasmalaktat jämfört med normoxi (r=0,98 vs. r=0,87). Större skillnad framgick för korrelationen mellan muskel- och plasmalaktat där hypoxi-försöket utgav starkare koefficient jämfört med normoxi (r=0,86 vs. r=0,59). Konklusion Sammanfattad data visar att hypoxi inte skapar större metabolisk respons vid intermittent styrketräning. Trots detta framkom tendenser som illustrerar att hypoxi kan påverka den metabola stressen under styrketräning. Däremot krävs vidare forskning för att kunna säkerställa effekten av hypoxi på kroppens metabola svar.
Ingår i Marcus Mobergs projekt: ”Resistance exercise under hypoxia and the acute molecular effects in human skeletal muscle

INTRODUCTION: Hypoxia is a potent stimulus that induces neuropsychological and physical impairments in humans. It is documented that ethnic differences exists across various physiological parameters. There appears to be a varying metabolic response across ethnicities, specifically African-Americans and Caucasians. Purpose: To further elucidate physiological and cognitive performance differences between African-American (AA) and Caucasian individuals (CAU) before, during or after hypoxic and normoxic exercise. Methods: Twelve college aged (18-25) apparently healthy African-American (six volunteers) and Caucasian (six subjects) males took part in two trials consisting of normobaric normoxia and normobaric hypoxia (12% oxygen). Each subject cycled at 50% of their altitude adjusted VO2max (-26% of normoxia VO2max) for one hour after a two-hour baseline. Subjects were monitored for cerebral and arterial O2 saturation, as well as the Trail Making Test A and B (TMT) psychomotor performance. Results: Arterial saturation proved to be significantly higher in AA (86.0±4.7) compared to CAU (79.5±4.8) during the first 60 minutes of exposure to hypoxia at rest (p=0.039), but not during exercise. Cerebral oxygenation to the left frontal lobe was decreased near the conclusion and 30 minutes after normoxic exercise. TMT B data revealed that CAU (79±12.7) had faster scores than the AA subjects (98±25.1) at all time points and was significantly different at the 115 minute time point of the hypoxic trial (p=0.024). Conclusion: Data suggests that before, during and after normobaric normoxia and hypoxia trial there is a differential response between AA and CAU in regards to arterial and cerebral oxygenation and psychomotor tests.

Arterial desaturation in fit athletes, during exercise at an intensity greater than or equal to 90% of VO₂ max has been reported by a number of authors yet the etiology of these changes remain obscure. Inadequate pulmonary ventilation due to a blunted respiratory drive, or lung mechanics has been implicated as a factor in the etiology of this phenomenon. It was the purpose of this experiment to investigate the relationship between arterial desaturation and ventilatory response to hypoxia (HVR). Twelve healthy male subjects ( age = 23.8 ± 3.6 yrs., height = 181.6 ±₋₁ 5.6 cms., Weight = 73.7 ± 6.2 kg., VO₂ max = 63.2 ± 2.2 ml .kg . -1 2 .min⁻¹) performed a five minute exercise test on a treadmill at 100% of VO₂ max. Arterial samples for pH, PCO₂, PO₂, and SaO₂ were withdrawn via an indwelling arterial cannula at rest and every 15s throughout the exercise test. The blood gas samples were analyzed with an Instrument Laboratories 1306 blood gas analyzer. Ventilation and VO₂ were measured by a Beckman metabolic measurement cart. On a separate occasion the ventilatory response to hypoxia (HVR) was determined by recording VE as progressive hypoxia was induced by adding N₂ to a mixing chamber. SaO₂ was measured using a Hewlett-Packard ear oximeter; to maintain isocapnia small ammounts of CO₂ were added to the open circuit system. ANOVA for repeated measured was used to evaluate changes in blood gases, ventilation, and VO₂. Simple linear regression and multiple linear regression was used to evaluate the relationship between the changes in SaO₂ and HVR and the descriptive variables. Subjects showed a significant decline in arterial saturation and PO₂ over the course of the test (p < 0.01,and p < 0.01). Four subjects (Mild) exhibited modest decreases in SaO₂ to (94.6 ± 1.9%), three (Moderate) showed an intermediate response (SaO₂ 91.6 ± 0.1%) and five (Marked) demonstrated a marked decrease in arterial saturation (SaO₂ = 90.0 + 1.2%). The differences in PO₂ and SaO₂ between Mild and Marked groups were significant ( p < 0.05, and p < 0.01); there were no significant differences between groups in VE, VO₂, pH or PCO . There was no significant correlation between the lowest SaO₂ reached and HVR, or any of the descriptive variables. Nine subjects did not reach maximal VE (as determined by the VO₂ max test) on the exercise test, two subjects 2 exhibited similar ventilation, and the remaining subject exceeded maximal VE, but fell into the Mild group with respect to desaturation. Oxygen uptake exceeded that recorded for the VO₂ max determination for four of the five subjects in the Marked group; the remaining subjects demonstrated lower or similar values. It was concluded that arterial desaturation was not related to blunted hypoxic drive.
Education, Faculty of
Curriculum and Pedagogy (EDCP), Department of
Graduate

This thesis is concerned with the role of iron in modulating right ventricular (RV) afterload during exercise in healthy people aged between 50 and 80 years. This is predicated on the requirement of the hypoxia-inducible factor (HIF) pathway for ferrous iron. A secondary objective is to examine the reactive oxygen species (ROS) hypothesis in human hypoxic pulmonary vasoconstriction (HPV) using exposure to hyperoxia. Chapters 3 and 4 describe basal relationships that may affect the HIF pathway and exercise capacity during ageing. These were explored in 113 participants using blood tests and exercise tests. Age and inflammatory factors, C-reactive protein, and ferritin were associated with impaired exercise capacity. In addition, ageing did not significantly affect haematological variables or iron status indicators. Chapters 5 and 6 describe the effect of a single intravenous iron infusion on the haematological variables in 32 participants in a randomised, placebo-controlled and double-blinded study. The effects of iron infusion on RV afterload during light exercise, and exercise capacity during heavy exercise, were examined in these participants. With iron infusion, erythropoietin production, and the increase in RV afterload during light exercise were blunted, potentially indicating involvement of the HIF pathway. However, blunting of RV afterload neither influenced the cardiac output during light exercise nor exercise capacity. Chapter 7 describes a study of 11 healthy volunteers, which investigated the ROS hypothesis in HPV using acute isocapnic hypoxia following an 8-hour exposure to hyperoxia. This sustained hyperoxic exposure did not influence the hypoxic behavior of the pulmonary vasculature. This thesis demonstrates the complex relationship between iron status and exercise capacity in older adults. It shows that the decrease in RV afterload during exercise caused by intravenous iron supplementation does not lead to an augmented cardiac output or exercise capacity. Finally, it calls into question the role of ROS in HPV.

Sodium bicarbonate (NaHCO3) is a pre-exercise alkalotic buffering agent that is ingested to alleviate accumulation of hydrogen anions during exercise. As such, this supplement has been extensively used in scientific literature to assess NaHCO3 ergogenic properties during high intensity exercise. These ergogenic properties are likely to be apparent when exercise perturbs the acid-base balance with excessive H+ accumulation; therefore, the lowest intensity at which NaHCO3 may exert an ergogenic effect is during exercise performed within the severe intensity domain. The physiological characteristics of severe intensity exercise include exacerbated rise in [bla], and therefore acid-base perturbations, until the termination of exercise. The environmental conditions can also have an additive physiological stress to exercise; indeed, acute hypoxia increases the relative energy contribution of anaerobic glycolysis. The resultant effect is an exacerbated rise in H+ during exercise, which may, at least in part, contribute to the ergolytic effect of acute hypoxia on exercise performance and capacity. As such, severe intensity exercise performed in acute hypoxic conditions may benefit from NaHCO3 ingestion to alleviate acidic stress and mitigate for the ergolytic effect of acute hypoxia. The purpose of this thesis was to evaluate the effect of NaHCO3 on severe intensity exercise performed in acute hypoxic conditions. Furthermore, this effect was evaluated through the parameter of the powerduration relationship (i.e. CP and W') during all-out, intermittent and constant load exercise to exhaustion. Together, this series of investigations are the first to demonstrate that NaHCO3 may be an effective ergogenic aid in acute moderate hypoxic conditions. In particular, this effect was observed during exercise in the severe intensity domain, with NaHCO3 enhancing the capacity of W' during all-out and constant load exercise; along with increasing volume of work that can be performed at this intensity during intermittent exercise. Indeed, Chapter six demonstrated that NaHCO3 may accelerate the rate of recovery during intermittent exercise when applied to the W'_bal model. Interestingly, this thesis is the first to identify the presence of an intensity dependant effect, with the magnitude of NaHCO3 ergogenicity diminishing as exercise intensity rises from the severe intensity domain to supra-maximal intensities. Further research should consider testing these hypotheses in alternative ambient conditions to determine the efficacy of NaHCO3 (e.g. in normoxic conditions or in combined extreme environmental conditions).

Strong evidence exists to support the use of a continuous (>8hr/day) hypoxic stimulus (either geographical altitude or simulated hypoxia) for enhancing the physical performance of endurance athletes. However, evidence supporting the use of acutely intermittent hypoxia (<1hr/day) for enhancing performance is less clear. The purpose of this study was to determine the effect of acutely intermittent hypoxic exposure on physiological and physical performance measures in team sport athletes. Using a single-blind controlled design, 14 trained basketball players (HYP = 7, CON = 7) were subjected to 15 days of intermittent hypoxia or normoxia. Each exposure was 37 minutes in duration (four cycles of 7min on, 3min off) and achieved using a nitrogen dilution device (Airo Ltd, Auckland, NZ). Prescribed peripheral oxygen saturation levels (SpO2) were maintained using an automatic biofeedback system and were progressively decreased from 86-89% on Day 1 to 75-78% on Day 15. A range of physiological measures and performance tests were conducted seven and two days before, and ten days after the intervention. The tests were: an incremental treadmill test to establish peak oxygen consumption ( peak) and running economy (RE), Yo-Yo Intermittent Recovery Test (YYIRT), and the Repeated High-Intensity Endurance Test (RHIET). Whole-blood samples were taken to assess a range of haematological measures. At 10 days post-intervention the HYP group, relative to the CON group, exhibited the following percent changes (±90% confidence limits, CL), and effect sizes (ES; ±90% CL); YYIRT running speedpeak (4.8; ± 1.6%, ES: 1.0 ± 0.4; benefit almost certain), RHIET total sprint time (-3.5; ± 1.6%; ES: -0.4 ± 0.2; benefit very likely), RHIET slowest sprint time (-5.0; ± 2.4%; ES: -0.5 ± 0.2; benefit very likely), soluble transferrin receptor (9.2; ± 10.1%; ES: 0.3 ± 0.3; benefit possible) running economy (11km.hr-1) (-9.0; ± 9.7%; ES: -0.7 ± 0.7; benefit likely, probable), and running economy (13km.hr-1) (-8.2; ± 6.9%; ES: -0.7 ± 0.5; benefit likely, probable). Changes to running economy (9km.hr-1), peak, maximum heart rate and lactate and all other blood measures were unclear. In conclusion, acutely intermittent hypoxia resulted in worthwhile changes in physical performance of trained basketball players in tests relevant to competition. However, the lack of clear change in physiological and haematological measures makes it difficult to determine the underlying mechanism for such enhancement.

Altitude training has been the subject of much research over the past forty year. However, research has focused on endurance performance and prolonged exposures to hypoxia have generally been employed to bring about improvements in performance. Few studies have investigated the responses to very short duration altitude exposures and its effects on performance. Moreover, research into the benefits of altitude training for improving the restoration of sprint performance during high intensity intermittent sports remains scarce. Therefore, this thesis aimed to determine the very acute responses to hypoxic exposure and the efficacy of repeated very short duration hypoxic exercise on recovery of sprint performance during intermittent activity. In addition, the thesis also aimed to determine the effect of such a training modality on oxidative stress levels and cellular damage during repeated sprint activity. Study one investigated the acute cerebral and skeletal oxygenation and cardiorespiratory responses to a single bout of very short duration (15 mm) hypoxic exposure (3048 m; F102 = 0.143) at rest and during exercise, and compared these to normoxic values. Both exercise conditions were performed at 65% of AP4lR max. The results of the study found that very short duration, hypoxic training stimulated significantly greater decreases in cerebral TOl over normoxic exercise (55.73 ± 2.77 and 64.02 ± 7.28%, respectively). Cerebral AHHb (31.07 ± 14.20 pmoFL 1 ) was also found to be significantly greater during hypoxic exercise than normoxic exercise (6.42 ± 8.04 pmoFLj and resting hypoxia (19.06 ± 7.40 pmohL 1 ). Skeletal TOI was not significantly different across all test conditions. However, skeletal AHH b (32.22 ± 20.81 pmolL 1 ) was significantly greater during hypoxic exercise than during resting hypoxia (10.23 ± 6.97 pmolL 1 ). Oxygen uptake and respiratory rate were not significantly different between normoxic and hypoxic exercise conditions, with mean V02 being 1.89 ± 0.03 and 1.83 ± 0.34 Lmin 1 for normoxic exercise and hypoxic exercise, respectively. Mean respiratory rates were 27.32 ± 6.27 and 24.63 ± 5.24 breaths.min for normoxic exercise and hypoxic exercise, respectively. These significant differences between conditions suggest greater 02 extraction rates during very short duration hypoxic exercise than during normoxic exercise or resting hypoxia. It was therefore proposed that a short course of very short duration hypoxic exposure may elicit improvements in the efficiency of 02 uptake and utilisation during intermittent exercise and subsequently lead to a reduction in oxidative stress during such activities. Resulting from the findings of study one, study two investigated the cerebral and skeletal oxygenation, cardiorespiratory and haematological changes in response to very short duration (15 mm) hypoxic training (HT) 3 times per week for three weeks compared to comparable normoxic training (NT). In addition, the study also evaluated the effectiveness of the hypoxic training programme on restoring sprint performance during an intermittent performance test (IPT) and the effects this protocol had on oxidative stress levels, as determined by MDA analysis. The results found that very short duration HT significantly increased RBC and F -id postintervention by 8.39% and 5.89% respectively, whilst Hb increase by 5.38% postintervention, though this was not to a level of significance. In contrast the NT group reported non-significant decreases post-intervention for Hb (3.36%) and RBC (0.61%), whilst Hd decreases significantly (5.31%). No significant differences were reported for MDA either pre or post-intervention or between groups. No significant differences were reported between the HT and NT groups or pre and post-intervention for any cerebral or skeletal tissue oxygenation variables. However, the HT showed greater increases in skeletal AHHb over the NT group during the sprint efforts of the IPT (79.99 ± 30.17 and 55.46 ± 29.00 pmolL 1 , respectively). Similar observations were also reported during the IPT's recovery periods, with mean AHHb being 64.53 ± 23.04 and 48.29 ± 28.31 pmoFL 1 , for the HI and NT groups, respectively. Additionally, no significant differences were found for sprint Wmean and Wak between the groups post-intervention. However, the HT group increased Wmean by 11.99% post-intervention compared to the 3.75% increase by the NT group. Comparable increases were also noted for W 3k, with the HT group improving 11.82% post —intervention and the NT group improving only 3.45%. No significant differences were found between the HI and NT groups or pre and post-intervention for V02 or respiratory rate during both sprint and recovery periods. However, the HI group generally showed non-significant decreases in both parameters, whilst the NT group showed no change from pre-intervention levels. This thesis found that despite significant improvements in haematological variables in the HT group over the NT group, very short duration hypoxic training does not improve the restoration of sprint performance during intermittent activity significantly more than comparable normoxic training. However, in general, the hypoxic training group did elicit greater levels of improvement. Thus, the results of this thesis may reflect more, the relatively low number of participants in the studies, and not that the changes reported were meaningless. Improvements of approximately 5% in blood parameters and almost 12% in power output are still likely to be of interest to the intermittent sports performer, as such improvements may make a difference during critical periods of a match or race.

The purposes of this study were 1) to investigate the release of cardiac biomarkers resulting from acute bouts of maximal intermittent exercise in a laboratory-based setting and set up an exercise-induced cardiac biomarker release (EICBR) model; 2) to compare the changes in cardiac biomarkers in normoxic and hypoxic environments and determine the effects of hypoxia; 3) to investigate the changes in oxidative stress biomarkers resulting from acute bouts of maximal intermittent exercise in normoxic and hypoxic environments at multiple time points; and 4) to observe the relationship between oxidative stress and EICBR and explore the hypothesis that lipid peroxidation triggers the release of cardiac biomarkers from the cytosolic pool. The maximal oxygen consumption (VO2max) and the corresponding velocity of VO2max (vVO2max) of ten well-trained male marathon runners (age 22.1±2.6 y, body mass 64.0±4.9 kg and height 177.3±3.9 cm) was determined under normoxic (FIO2=21.0%, VO2max_N=64.72±5.63 ml∙kg-1∙min-1 and vVO2max_N=18.2±1.0 km∙h-1) and hypoxic (FIO2=14.4%, VO2max_H=62.16±6.74 ml∙kg-1∙min-1 and vVO2max_H=16.7±0.7 km∙h-1) conditions in two experimental trials. One set of conditions was tested in each trial. The order in which each participant faced each trial was selected at random and the trials were separated by 72 h. The ten participants also completed three maximal intermittent exercise protocols, under normoxic (trial N, FIO2=21.0%), absolutely hypoxic (trial AH, FIO2=14.4%) and relatively hypoxic (trial RH, FIO2=14.4%) conditions. The order in which the participants faced the three conditions was once again selected at random and the protocols were separated by at least 7 d. Each bout of maximal intermittent exercise in trials N and AH consisted of a hard run of 16.4±0.9 km∙h-1 (90% vVO2max_N) for 2 min, followed by an easy run of 9.1±0.5 km∙h-1 (50% vVO2max_N) for 2 min with a 2% slope. In trial RH, each bout of exercise consisted of a hard run of 15.0±0.6 km∙h-1 (90% vVO2max_H) for 2 min, followed by an easy run of 8.4±0.3 km∙h-1 (50% vVO2max_H) for 2 min with a 2% slope. Each of the three trials consisted of 23 bouts of maximal intermittent exercise, performed over 92 min. Measurements of the serum of the antecubital venous blood were performed pre- and post- (0 h, 2 h, 4 h and 24 h) exercise. The measurements were taken at five time points for each of the three conditions. The cardiac damage biomarkers of high sensitivity cardiac troponin T (hs-cTnT) and cardiac troponin I (cTnI) and the oxidative stress biomarkers of malondialdehyde (MDA), lipid hydroperoxide (LH), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and total antioxidant capacity (TAOC) were analysed. Heart rate (HR) and arterial oxygen saturation (SaO2) were recorded before and during exercise. Due to the skewed distribution of the data (P<0.05), a non-parametric Friedman’s test was used to compare the differences in the levels of hs-cTnT and cTnI between pre- and post-exercise and at each time point for the three conditions. MDA, LH, SOD, CAT, GSH, TAOC and HR were normally distributed (P>0.05) and were analysed using one-way repeated ANOVA tests. Pearson’s product moment correlation coefficients were used to determine the degree of association between the peak levels of hs-cTnT and cTnI, and MDA, LH, SOD, CAT, GSH and TAOC. In trial N, the level of hs-cTnT was elevated 0 h post-exercise (9.628±3.797 pg∙ml-1 was significantly different from the pre-exercise level of 5.118±1.857 pg∙ml-1, P=0.005), reached its peak level 2 h post-exercise (24.290±18.628 pg∙ml-1 was significantly different from the pre-exercise level, P=0.005) and returned to the baseline level at 24 h post-exercise (5.978±1.849 pg∙ml-1). The peak levels of hs-cTnT (N, AH 37.001±31.995 pg∙ml-1, RH 28.614±23.628 pg∙ml-1) and cTnI (N 0.0375±0.0437 ng∙ml-1, AH 0.0475±0.0533 ng∙ml-1, RH 0.0345±0.0375 ng∙ml-1) did not significantly differ under the three conditions. In trial AH, the peak levels of hs-cTnT (2 h, 4 h) and cTnI (2 h, 4 h) were highly related to the MDA_0h and the TAOC_24h. In trial RH, the peak levels of hs-cTnT (2 h, 4 h) and cTnI (2 h, 4 h) were highly related to the TAOC_4h. It was concluded that maximal intermittent exercise can be used to trigger EICBR. The stimulus of hypoxia did not induce more cardiac damage in this exercise model. Maximal intermittent exercise potentially triggers EICBR through oxidative stress, especially lipid peroxidation. Keywords: cardiac biomarkers, hs-cTnT, cTnI, oxidative stress, hypoxia

Chez l'homme, l'hypoxie correspond à une inadéquation entre les besoins tissulaires et les apports en oxygène. Cet état est une caractéristique commune à l'exposition à l'altitude et au syndrome d'apnées obstructives du sommeil (SAOS), bien que celle-ci soit continue dans le premier cas et intermittente et nocturne dans le second.L'hypoxie d'altitude entraine une altération des performances cognitives et motrices. La réduction de la performance à l'exercice en altitude a longtemps été attribuée à une altération du métabolisme musculaire du fait d'une réduction de l'apport en oxygène. Les perturbations cérébrales induites par l'hypoxie pourraient également avoir un rôle majeur dans cette limitation.Le SAOS, véritable enjeu de santé publique, est associé à des troubles cognitifs pouvant ainsi influencer le fonctionnement quotidien des patients souffrant de ce syndrome et résulter en une somnolence diurne excessive, une baisse de la qualité de vie ou encore une réduction de la productivité au travail et des performances scolaires. Le fait que ces altérations cérébrales puissent influencer les capacités motrices et à l'effort des patients atteints d’apnées obstructives du sommeil reste en revanche à investiguer.Au cours de ce travail de thèse, nous nous sommes intéressés à deux modèles d’exposition hypoxique et à leurs conséquences cérébrales et neuromusculaires. Nous avons tout d’abord étudié l'effet d'une exposition à l'hypoxie d'altitude aigue (quelques heures) et prolongée (plusieurs jours) sur la fonction neuromusculaire et ses répercussions à l'exercice chez le sujet sain. Nous avons ensuite étudié l'influence du modèle d'hypoxie intermittente associé au SAOS sur la fonction neuromusculaire et la tolérance à l'exercice de ces patients. Nous avons ainsi cherché à caractériser les altérations cérébrales à l'exercice en lien avec ce syndrome et leur réversibilité suite à un traitement en ventilation par pression positive continue.Chez le sujet sain, nous avons démontré que la performance à l'exercice impliquant une masse musculaire réduite (fléchisseurs du coude) n'était pas limitée par une fatigue centrale accrue après 1 et 5 jours d'exposition à une altitude de 4350 m. Nous avons mis en évidence que la dysfonction musculaire (force et endurance réduites) observée chez le patient SAOS est associée à un déficit d'activation supraspinal et une augmentation de l'inhibition intracorticale. De plus, nos résultats suggèrent qu'une altération de la réponse cérébrovasculaire à l'exercice puissent impacter négativement la tolérance à l'exercice des patients souffrant d'un SAOS sévère. Ces altérations neuromusculaires et cérébrovasculaires n'étaient pas corrigées après un traitement de huit semaines par ventilation nocturne en pression positive continue soulignant la nature persistante de ces altérations cérébrales
In humans, hypoxia is defined as the mismatch between tissue requirement and oxygen delivery. This condition is a common feature between high-altitude exposure and obstructive sleep apnea syndrome (OSA), although it is continuous in the first instance and intermittent and nocturnal in the second one.High-altitude exposure causes an impairment in cognitive and motor performance. The reduction in exercise performance observed under hypoxic condition has been mainly attributed to altered muscle metabolism due to impaired oxygen delivery. However, hypoxia-induced cerebral perturbations may also play a major role in exercise limitation.OSA, a major public health concern, is associated with cognitive impairment that can alter patients' daytime functioning and result in excessive daytime sleepiness, reduced quality of life and lowered work productivity and school performance. The fact that these cerebral alterations can influence motor and exercise performance in patients with obstructive sleep apnea remains to be investigated.In this thesis, we investigated two different models of hypoxic exposure and their cerebral and neuromuscular consequences. First, we assessed the effect of acute (several hours) and prolonged (several days) high-altitude exposure on the neuromuscular function and its repercussions during exercise in healthy subject. Then, we then investigated the model of intermittent hypoxia associated with OSA and its influence on the neuromuscular function and exercise tolerance in these patients. We seeked to characterize cerebral alterations during exercise associated with this syndrome and their reversibility following continuous positive airway pressure treatment.In healthy subject, we showed that exercise performance involving a small muscle mass (elbow flexors) was not limited by an exacerbated amount of central fatigue after 1 and 5 days of high-altitude exposure (4,350 m). We highlighted that muscle dysfunction (reduced strength and endurance) was associated with a supraspinal activation deficit and an increase in intracortical inhibition. Moreover, our results suggest that an alteration in cerebrovascular response during exercise may contribute to reduced exercise tolerance observed in patients with severe OSA syndrome. The neuromuscular and cerebrovascular abnormalities were not reversed following an eight-week continuous positive airway pressure treatment, highlighting the persistent nature of the cerebral alterations

Hypoxia is defined as a deficiency in the amount of oxygen reaching the tissues, and is a common problem in critically ill patients. It is not currently possible to predict how well an individual will adapt to hypoxic conditions, and patients presenting with hypoxia are often treated with supplemental oxygen. However, this blanket-treatment approach is not suitable in all cases and a more personalised approach is required. My thesis project builds on information acquired during the Caudwell Xtreme Everest (CXE 2007) expedition, where over 200 volunteers trekked to Everest Base Camp. CXE uses studies on healthy volunteers exposed to extreme environments to aid in the understanding of the complicated issues concerned with critical illness, and aims to use these findings to improve the treatment of critically ill patients, without putting them directly at risk. My thesis project has combined physiological information acquired during CXE with biochemical information measured in plasma samples taken during CXE. Performance at altitude has been used as a proxy for hypoxia adaptation, with individuals who show a small loss of performance at altitude compared to London assumed to be adapting better compared to individuals who show a larger loss. Analysis of the physiological and biochemical data for a core group of 24 individuals has culminated in the application of multiple linear regression to produce a number of models capable of predicting the key changes in physiological response as a function of a number of biochemical metabolites. These models have been used to identify a set of biochemical metabolites to measure in a further 190 individuals, to allow validation and training of the models on a larger sample size. These models can then be adapted for use in a critical illness environment, to allow the prediction of how well an individual will adapt to hypoxic conditions.

Intermittent hypoxia (IH) is broadly defined as repeatedly breathing decreased amounts of oxygen (hypoxia) interspersed with periods of room air breathing (normoxia). In animal, human diseased, and healthy human models, research has shown IH to negatively affect cerebrovascular vessel dilation. We have previously shown poikilocapnic (uncontrolled carbon dioxide (CO₂)) IH to blunt the vasodilatory response of a cerebral vessel during acute hypoxia. The purpose of this study was to measure the ventilatory, cardiovascular and cerebrovascular responses to: I) acute hypoxia and; II) to submaximal exercise following an isocapnic (controlled CO₂) IH protocol. Healthy males (n = 9) with normal pulmonary function underwent 10 consecutive days of isocapnic IH (oxyhaemoglobin saturation (SaO₂) = 80%, 1 hr/day). Ventilatory, cardiovascular, and cerebrovascular (transcranial Doppler) responses to acute isocapnic hypoxia (SaO₂ = 80%, 5 minutes) were measured before (PRE-IH) and after (POST-IH) IH. Also, ventilatory, cardiovascular, and cerebrovascular parameters were measured during a submaximal cycle exercise test (50, 100, 150 watts) PRE-IH and POST-IH. To further investigate cerebrovascular regulation during exercise, 5% CO₂ was added for two minutes of each exercise stage. Over the 10 days of IH, there was a significant increase in minute ventilation (VE) during the IH bouts (p<0.05). IH did not significantly alter the ventilatory, cardiovascular, and cerebrovascular responses to acute hypoxia. However, there was a significant association (r = 0.86, p<0.05) between the change in the mean arterial blood pressure (MAP) and mean middle cerebral arterial blood flow velocity (MCAVm) responses to acute hypoxia. Exercise caused significant increases in VE , MCAVm, and MAP (p<0.05), but there were no differences in measured variables between PRE-IH and POST-IH exercise trials (p>0.05). Similarly, hypercapnia caused significant increases in VE and MCAVm (p<0.05), although the magnitude of the response did not change following IH. Our results suggest that the effect of IH on ventilatory, cardiovascular, and cerebrovascular regulation during acute hypoxia is individualistic, and changes in the MAP response may strongly influence the changes in cerebral blood flow (CBF). Also, our results suggest that IH does not alter ventilatory, cardiovascular, or cerebrovascular regulation during submaximal exercise or responsiveness to hypercapnia.
Education, Faculty of
Kinesiology, School of
Graduate

Le maintien ou le renforcement de la masse et de la fonction musculaire, altérées chez les patients BPCO, est un objectif primordial pour préserver, voire améliorer leur tolérance à l'effort, leur qualité de vie et leur survie. Afin d'optimiser la prise en charge de cette dysfonction musculaire, la réhabilitation est complétée par des interventions nutritionnelles, encore appelées réhabilitations nutritionnelles. Dans ce contexte, l'apport d'acides gras polyinsaturés de la série n-3, et plus particulièrement d'acide docosahexaénoïque (DHA), pourrait s'avérer intéressant en raison de leurs effets bénéfiques démontrés dans plusieurs pathologies chroniques. L'objectif de ce travail était donc de caractériser les effets d'une supplémentation en DHA sur la tolérance à l'effort et sur le métabolisme énergétique des muscles squelettiques de rats adultes exposés à une hypoxie comme modèle de muscle de patient BPCO au stade de l'insuffisance respiratoire chronique. La tolérance à l'effort est améliorée par le DHA, que les rats soient conditionnés en normoxie ou en hypoxie. En normoxie, les mécanismes impliqués seraient liés à un effet du DHA mimétique de celui d'un exercice d'endurance, avec une activation de l'AMPK et une amélioration de la fonction mitochondriale étudiée sur fibres musculaires perméabilisées. En hypoxie, le DHA agirait différemment, réduisant les effets de l'hypoxie sur le muscle, sans que les mécanismes mimétiques de l'exercice d'endurance ne soient clairement retrouvés. La prise de DHA chez des rats entrainés et conditionnés en hypoxie permet également un gain d'endurance mais les mécanismes à l'origine de cet effet ne sont pas élucidés et nécessitent des travaux complémentaires. Au vu des résultats sur le muscle, la supplémentation en DHA pourrait donc être bénéfique dans la prise en charge de la dysfonction musculaire dans les maladies chroniques telles que la BPCO.

The present study investigated the hypothesis that maximal voluntary contractions (MVC) peak torque, VJ, muscle tenderness, and plasma creatine activity would be significantly less for the condition that subjects were exposed to hypoxic (H) condition for 4 hours after eccentric exercise compared with the normoxic (N) condition.

The present study investigated the hypothesis that maximal voluntary contractions (MVC) peak torque, VJ, muscle tenderness, and plasma creatine activity would be significantly less for the condition that subjects were exposed to hypoxic (H) condition for 4 hours after eccentric exercise compared with the normoxic (N) condition.

This study sought to determine the independent influence of hypoxia on thermoregulatory responses to exercise in compensable and uncompensable hot conditions. Eight participants completed three experimental trials of cycling in either normoxia (21% O2) or hypoxia (13% O2) in order to manipulate relative exercise intensity (%VO2peak), since VO2peak was reduced by ~30% in hypoxia. When trials were matched for %VO2peak, changes in core temperature and local sweat rates (LSR) were significantly lower in the hypoxic trial as a result of a lower rate of metabolic heat production (Hprod) in order to maintain a similar %VO2peak compared to normoxia. However, when Hprod was fixed between normoxic and hypoxic trials the systematic differences in core temperature and LSR were eliminated. Conversely, at a fixed Hprod skin blood flow (SkBF) was greater in hypoxia compared to normoxia by ~40%. Despite improvements in SkBF, the potential for maximum heat loss was unaffected during an incremental humidity ramp protocol, resulting in no difference between normoxia and hypoxia in the critical ambient vapour pressures at which core temperature inflected upwards. These data further demonstrate, using a within-subjects design, that metabolic heat production, irrespective of large differences in %VO2peak, determines thermoregulatory responses during exercise. Furthermore, this study suggests that the influence of large differences in skin blood flow on heat dissipation may be lesser than previously thought.

Introduction: Haemostasis is the arrest of bleeding. In recent years, in-vitro studies have suggested that secondary haemostasis (blood coagulation) is subject to activation by reactive oxygen species (ROS). It is known that patients who suffer from vascular disease are typically hypoxaemic and in the case of peripheral occlusive artery disease (POAD), physical exercise is used to improve symptom free mobility in the affected limbs. Hypoxia and physical exercise are two potent independent and synergistic initiators of ROS. We identified a clear need for in-vivo analysis of this novel area of research. Aims: There were two main aims of this research. 1. To explore the in-vivo influences of inspiratory hypoxia and physical exercise on biomarkers of haemostasis; and in doing so and subsequently carry out a randomised double blind placebo control trial to explore the interaction between oxidative stress (ROS accumulation) and haemostasis. Hypothesis: It was hypothesised that hypoxia and exercise would be independently and synergistically associated with an increase in oxidative stress, resulting in coagulation activation. We hypothesised that intervention with free radical reaction-chain breaking antioxidant vitamins would attenuate oxidative stress and thus attenuate the activation of coagulation. Methods: study 1 - Healthy males were subjected to six hours of normobaric hypoxia (12% inspired oxygen) and then a physical exercise challenge to exhaustion (cycling ramp-test). Citrated plasma was collected pre hypoxic exposure, post six hours of exposure, then immediately post exercise and analysed for routine clinical markers of coagulation (aPTT, PT, TT and fibrinogen) and analysed with and without correction for plasma volume shift. Data were analysed using a one-factor repeated measures ANOVA incorporating one within (condition: time point) subjects factor. Following a significant main effect and interaction, paired samples t-tests were employed to make post hoc comparisons at each level of the within-subjects factor. Study! - Healthy males were subjected to a double blind, randomised, placebo controlled intervention with vitamin C (a water soluble) and vitamin E (a lipid soluble), two ROS-scavenging, chain breaking antioxidants. The intervention lasted eight weeks to insure membrane enrichment with antioxidants. The methods of study one were repeated but with a pre-intervention time point added and the addition of two extra markers of thrombin generation (PF1+2 and T-AT). Data were analysed using a two-factor mixed ANOVA incorporating one between (group: antioxidant intervention vs. placebo control) and one within (condition: time point) subjects factor. Following a significant main effect and interaction, a paired samples t-test was used to make post hoc comparisons at each level of the within-subjects factor, with the alpha level Bonferroni corrected for multiple comparisons Between-group comparisons were assessed using independent samples t-tcsts applied to each level of the between-subjects factor. Results: Study 1 - Hypoxia was not associated with activation of coagulation. Physical exercise increased the activity of contact factor coagulation pathway activation. Study 2 - The intervention increased thrombin generation in the antioxidant group. This was met with an antagonistic antithrombin activation. Hypoxia did not impact the placebo group, but normalised the thrombin generation of the antioxidant group. Physical exercise increased contact factor pathway (CFP) as per study 1, but thrombin generation was unaltered. Hypoxia suppressed fibrinolysis post exercise, which is known to be activated in normoxic exercise. Discussion: hi study one, hypoxia alone did not activate coagulation. We hypothesised that this could be tentative evidence of a ROS concentration threshold for activation since once exercise was superimposed the accumulation of ROS activated the CFP. Correction for changes in plasma volume nullified the increased activity of the CFP. Corrections for shifts in plasma volume are routinely ignored in the literature and this was a novel finding. Study 2 was the first intervention of its kind. The increase in thrombin generation pre-post intervention with antioxidants suggests compelling evidence of in-vivo regulation of coagulation by ROS. But the direction of change was completely contrary to the original hypothesis. The confirmation that hypoxia does not activate coagulation is important, especially given the controversy surrounding long-haul flight deep vein thrombosis. Interestingly, exercise did not increase thrombin generation, despite the increase in the CFP. These findings suggest haemostasis is indeed subject to control by the body's redox state invivo via an as of yet, unknown mechanism.

Muscle mass adapts in response to changing functional and metabolic demands of the organism and its maintenance is important for movement, health and survival. However, many questions remain regarding the acute response of muscle to feeding, exercise and altered environmental conditions. Thus, the aim of the present thesis was to investigate how muscle responds acutely to changes in some of these stimuli in humans.

Les fonctions cardiovasculaires doivent répondre à des stimulations physiologiques importantes et différentes lors de l'exercice physique, de l'exposition à la haute altitude ou de tests de stimulation spécifiques du système nerveux autonome. Nous avons dans ce travail de thèse, étudié les modulations autonomiques consécutives à l'exercice (entraînements / compétition ou réentraînement), à l'hypoxie ou à des tests de stimulation adrénergiques afin de faire le lien avec la fatigue et/ou la limitation à l'effort. Le suivi de coureurs à pieds séniors nous a permis d'observer une majoration de l'activité sympathique ainsi qu'une diminution du tonus parasympathique sous l'effet de l'entraînement, et plus encore de la compétition. Dans un second temps, nous avons analysé les réponses adaptatives de sujets exposés à une hypoxie brutale par le biais de tests d'orthostatisme, et mis en évidence une dysautonomie transitoire les deux premiers jours d'exposition à l'altitude, suivie d'un retour vers des valeurs basales le quatrième jour. Notre troisième protocole a montré que les fibromyalgiques présentent une qualité de vie et une capacité d'exercice altérées ainsi que des réponses autonomiques à l'orthostatisme émoussées comparées à des sujets témoins. Cependant, un entraînement en endurance de 12 semaines à intensité modérée, semble bénéfique sur la qualité de vie des patientes, et améliore les paramètres d'exercice et de modulation de l'activité du système nerveux. Enfin, nous avons confirmé que les sujets trisomiques présentaient une capacité d'exercice ainsi qu'une fonction cardio-respiratoire altérées par rapport à des sujets contrôles appariés en âge. Les tests de stimulations du système nerveux autonome montrent aussi une dysautonomie marquée, avec des réponses autonomiques émoussées qui peuvent être mises en lien avec une capacité d'effort limitée et/ou l'apparition d'une fatigue précoce à l'effort chez les trisomiques 21. Notre travail, par l'analyse de la variabilité cardiaque, a donc permis de mettre en évidence des altérations de l'activité autonomique qui peuvent être durables ou transitoires, selon l'environnement, selon le niveau d'activité ou l'existence de pathologies.

Thesis (Ph. D.)--University of California, San Diego, 2006.
Title from first page of PDF file (viewed June 5, 2006). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.

The central nervous system is highly sensitive to reductions in oxygen availability but the neurophysiological responses in healthy human lowlanders are not well understood. In severe hypoxia, whole-body exercise tolerance is impaired and neuromuscular fatigue, defined as any exercise-induced reduction in the ability of a muscle to generate force or power, reversible by rest, may be largely due to cerebral perturbations. The primary aim of this thesis was to determine the mechanisms of exercise-induced neuromuscular fatigue and the related neurophysiological responses to acute, chronic and intermittent severe hypoxia in healthy humans. In acute severe hypoxia (AH), exercise tolerance was, in part, mediated by a hypoxia-sensitive source of central fatigue, measured as a decrease in voluntary activation (VA) of the knee extensors (Study 1 – 4). This coincided with a significant challenge to systemic (arterial oxygen saturation [SpO2] ≈ 70%, Study 1 - 4) and cerebral oxygen availability at end-exercise (Study 3 - 4). The rate of development of peripheral locomotor muscle fatigue was blunted at task failure in AH in comparison to normoxia (Study 1 – 2). Corticospinal excitability and the neuromuscular mechanisms of fatigue were measured after a prolonged (two-week) exposure to high altitude in Study 3 (5260 m above sea level, Mount Chacaltaya, Bolivia). This was the first study to show that acclimatisation to chronic severe hypoxia (CH) alleviates the development of supraspinal fatigue induced by whole-body exercise in AH. This occurred in parallel to an improved cerebral oxygen delivery and cerebral oxygenation. Interestingly, the neurophysiological responses at rest in CH were characterised by an increased corticospinal and muscle membrane excitability. The peripheral contribution to neuromuscular fatigue was not attenuated following acclimatisation to high altitude. In study 4, a two-week protocol of intermittent hypoxia (IH) attenuated exercise-induced supraspinal fatigue measured in AH and substantially improved constant-power cycling in severe hypoxia. Total haemoglobin mass was unaltered by IH, but arterial oxygen content was improved due to an increase in SpO2, secondary to an enhanced ventilatory response to exercise. Peripheral locomotor muscle fatigue was lower following IH, which may be related to exercise training in hypoxia. Although corticospinal excitability was unchanged following a single 2-h exposure to severe hypoxia, repeated exposures of IH resulted in a transient increase in motor cortex excitability without changes in intracortical inhibition. (Study 5). In conclusion, in acute severe hypoxia, whole-body exercise tolerance is impaired through oxygensensitive mechanisms which exacerbate central fatigue. The acute response can be alleviated following both chronic and intermittent severe hypoxia.

INTRODUCTION It is well established that both hypoxia and metaboreflex have a great impact on the cardiovascular system, exerting both contrasting and complementary effects on heart rate (HR), cardiac output (CO), ventilation (VE), stroke volume (SV) and systemic vascular resistance (SVR). However, evidence on the interaction between hypoxia and metaboreflex when concomitantly active is still lacking. The aim of my study was to better elucidate this topic, focusing on hemodynamic parameters that have never been studied in the past in this context (like SV, BP, and SVR). To reach this goal, I performed 2 series of experiments in which were evaluated the effects of a previous dynamic exercise bout in hypoxia (Experiment 1) and the simultaneous exposure to hypoxia (Experiment 2) on metaboreflex activation. MATERIALS AND METHODS Experiment 1 was conducted recruiting 17 well-trained subjects (7 females, 10 males) that underwent a cardiopulmonary exercise test (CPET) to asses their fitness. Then, the athletes performed a 10-minute rectangular exercise bout on a cycle ergometer in normoxia and in normobaric hypoxia at two different levels of fraction of inspired oxygen (15,5% and 13,5 % of FiO2 ) in three separate days after randomization. Each exercise session was followed by a metaboreflex-activating protocol in normoxia that consisted of 2 sessions called post-exercise muscle ischemia (PEMI) and control exercise recovery (CER). PEMI and CER both included 3 minutes of rest and 3 minutes of exercise at 30% of the maximum wattage (Wmax) reached during the CPET. After the exercise, PEMI was followed by a 3-minute application of an inflatable thigh cuff to induce a temporary occlusion of the arterial and venous vascular bed and 3 minutes of rest. Regarding CER, the exercise was followed by 6 minutes of resting without occlusion and was used as control. In experiment 2, 11 moderately-fit male subjects were recruited. After CPET, the subjects underwent a PEMI/CER session in normoxia and hypoxia (13,5 % of FiO2 ) in 2 separate days. The variables analyzed in experiment 1 and 2 were SV, CO, HR, ventricular filling rate (VFR, a measure of cardiac diastolic function/preload) and ventricular ejection rate (VER a measure of cardiac inotropism) by means of impedance cardiography, mean BP by manual sphygmomanometer and SVR indirectly from CO and BP according to Poiseuille's law. Moreover, I measured cerebral tissue oxygenation (COX) and peripheral hemoglobin saturation (SPO2) by means of near-infrared spectroscopy (NIRS) throughout all the experimental sessions to check if the hypoxia was effective.    RESULTS In both experiments 1 and 2, I evidenced a significant reduction of SV, CO and VFR response during metaboreflex activation when the hypoxic stimulus was applied while SVR response was increased preventing BP from dropping as a consequence of SV reduction. DISCUSSION My results demonstrate that hypoxia can impair SV response to metaboreflex activation. This mechanism is likely related to a reduced left ventricular (LV) preload as VFR decreased when the hypoxic stimulus was applied. Two possible explanations could be proposed to explain my results. Firstly, hypoxia could have stimulated nitric oxide (NO) production in the venous vascular bed with a consequent venodilation and reduced venous return to the heart, impairing the recruitment of the Frank-Starling mechanism to increase SV. Secondly, hypoxia has a vasoconstrictor effect on the pulmonary arterial bed that could have increased right ventricular (RV) afterload, reducing the amount of blood returning to the LV from the pulmonary vascular bed and impairing LV preload. Moreover, SVR response increased both in experiments 1 and 2, counterbalancing the potential BP drop that could have taken place as a consequence of SV reduction. Thus, it can be speculated that metaboreflex activation overcame the vasodilatory effect of hypoxia-mediated NO production on peripheral arteries.​

Fatigue is defined as an exercise-induced decrease in maximal voluntary force produced by a muscle. Fatigue may arise from central and/or peripheral mechanisms. Supraspinal fatigue (a component of central fatigue) is defined as a suboptimal output from the motor cortex and measured using transcranial magnetic stimulation (TMS). Reductions in O2 supply (hypoxia) exacerbate fatigue and as the severity of hypoxia increases, central mechanisms of fatigue are thought to contribute more to exercise intolerance. In study 1, the feasibility of TMS to measure cortical voluntary activation and supraspinal fatigue of human knee-extensors was determined. TMS produced reliable measurements of cortical voluntary activation within- and between-days, and enabled the assessment of supraspinal fatigue. In study 2, the mechanisms of fatigue during single-limb exercise in normoxia (arterial O2 saturation [SaO2] ~98%), and mild to severe hypoxia (SaO2 93-80%) were determined. Hypoxia did not alter neuromuscular function or cortical voluntary activation of the knee-extensors at rest, despite large reductions in cerebral oxygenation. Maximal force declined by ~30% after single-limb exercise in all conditions, despite reduced exercise time in severe-hypoxia compared to normoxia (15.9 ± 5.4 vs. 24.7 ± 5.5 min; p < 0.05). Peripheral mechanisms of fatigue contributed more to the reduction in force generating capacity of the knee-extensors following single-limb exercise in normoxia and mild- to moderate-hypoxia, whereas supraspinal fatigue played a greater role in severe-hypoxia. In study 3, the effect of constant-load cycling exercise to the limit of tolerance in hypoxia (SaO2 ~80%) and normoxia was investigated. Time to the limit of tolerance was significantly shorter in hypoxia compared to normoxia (3.6 ± 1.3 vs. 8.1 ± 2.9 min; p < 0.001). The reductions in maximal voluntary force and knee-extensor twitch force at task-failure were not different in hypoxia compared to normoxia. However, the level of supraspinal fatigue was exacerbated in hypoxia, and occurred in parallel with reductions in cerebral oxygenation and O2 delivery. Supraspinal fatigue contributes to the decrease in whole-body exercise tolerance in hypoxia, presumably as a consequence of inadequate O2 delivery to the brain.

We tested the hypothesis that decrements in arterial oxyhaemoglobin saturation could be related to elevations in circulating endothelin-1 following 30 minutes of exercise at ventilatory threshold. Eight aerobically trained males (mean ± SEM: age 26.14 ± 1.77 years, height 182.36 ± 1 . 5 1 cm, mass 72.89 ± 2.62 kg) completed 2 maximal exercise tests (mean ± SEM: normoxia (n) 68.56 ± 2.06 mL.kg-¹min-¹; hypoxia (Fi02 0.14)(h) 53.88 ± 1.35 mL.kg-¹.min-¹), and two 30-minute steady state exercise protocols at the power achieved at threshold during maximal exercise tests (mean ± SEM: power (Watts) 257.14 ± 21.57 (n) 191.25 ± 10.79 (Fi02 0.14)(h); HR (bpm) 161.7 ± 5.34 (n) 156.6 ± 3.45 (h)). When participants exercised for 30 minutes at ventilatory threshold inspiring 14%02, a significant decrease in oxygen saturation (as measured by pulse oximetry) was observed, when compared to values in normoxia (80.2 ± 1.17 % (h) vs 94.12 ± 0.24 % (n); p<0.001). This desaturation was not accompanied by significant changes in plasma endothelin-1 (ET-1), big endothelin-1 (BigET-1) or nitric oxide (NO). Both pulmonary artery pressure (PAP) and oscillatory compliance (OC) were significantly greater following exercise (F[superscript omitted] = 4.74 p< 0.05), compared to pre-exercise values. These outcome variables were not different between normoxia and hypoxia. Plasma ET-1 or BigET-1 levels did not differ significantly over time or across conditions F[superscript omitted] = 4.74 p> 0.05). In conclusion, plasma ET-1 levels following 30-minutes of steady state exercise at ventilatory threshold are unrelated to decrements in oxyhaemoglobin saturation.
Education, Faculty of
Kinesiology, School of
Graduate

Previous research suggests that physical activity may result in to decreases in arterial saturation (SaO2) and cerebral blood flow when exposed to a low oxygen environment between aerobically fit and unfit males. Purpose: The purpose of this study was to determine differences in SaO2, cerebral blood flow, minute ventilation (VE), and blood lactate between fit and unfit young males during exercise in hypoxia compared to normoxia. Methods: Apparently healthy college age males took part in two trials consisting of normobaric normoxia and normobaric hypoxia (12% oxygen). Fit (n = 3; VO _2max = 51.5 ml • kg^-1 • min^-1 ± 3.1) and Unfit (n = 3; VO_2max = 34.4 ml • kg ^-1 • min^-1 ± 5.6) males cycled at 50% of their altitude adjusted VO_2max (-26% of normoxia VO_2max) for one hour after a two-hour baseline. Results: SaO ₂, cerebral blood flow, and RER were significantly decreased during hypoxia in all subjects (P < 0.05), but did not differ between groups. An interaction showed that Fit subjects had a higher SaO₂ during exercise in hypoxia (P < 0.05). V_E and lactate was greater during hypoxia (P < 0.05). The Fit group demonstrated a higher V _E during exercise in hypoxia (P < 0.05). No differences in blood lactate were found between the two groups. Conclusion: The data suggests that when exposed to hypoxia aerobically unfit males may demonstrate decrements in oxygen utilization which may lead to decreases in physical activity and/or performance.

Physiological adaptation to environmental stressors is often studied in isolation, but these stressors are frequently combined outside of laboratory settings, for example cold and hypoxia at altitude. There is also limited information about the effect that adaptation to one environment has on exposure to another. The five studies in this thesis were conducted in humans to assess the effect cold habituation has on the response to a simulated hypoxic exposure, and also to investigate a possible mechanism through which any change may occur. A possible site for the 'cross-adaptation' between cold habituation and hypoxia is the autonomic nervous system. Heart rate variability (HRV) is an non-invasive measurement technique which has been used to quantify autonomic activity. The two main frequency bands of interest when using HRV are referred to as the Low-Frequency (LF) band (the power found between 0.04 and 0.15 Hz) and the High-Frequency (HF) band (the power found between 0.15 and 0.4 Hz). Study One assessed the reliability of heart rate variability as a technique to indicate autonomic activity during both paced (breathing in time to a standard audible signal) and spontaneous breathing conditions, and at different cycling exercise intensities in a thermoneutral environment. It was hypothesised that within each condition HRV indices would be reliable between repeated recordings, which were separated by 96 hours. Eight participants performed each condition on the two occasions. Analysis of the data (coefficients of variation [CV] and intraclass correlation coefficients [ICC]) showed that the paced breathing condition was the most reliable condition, and time domain HRV indices were reliable, whilst not all frequency domain HRV indices were. Normalising and log transforming the raw data did improve reliability and log transformed total and high frequency (Ln HF) power and low:high frequency ratio (Ln LF:HF) met the a priori criteria (CV <10 % and ICC > r=0.8). It was concluded that most log transformed HRV indices were reliable at rest, during paced breathing and during moderate intensity exercise. Thus, the hypothesis was accepted, but caution was advised as several of the indices were close to exceeding the reliability criteria (Ln total power, Ln HF and Ln LF:HF) and a second autonomic measurement technique may be considered to substantiate its use. The previous study identified that Ln HF power increased when breathing frequency was reduced at rest. Study Two investigated the effect that alterations in breathing patterns had on HRV indices during rest and unloaded seated cycle ergometery (0 Watts) in 16 male participants. It was hypothesised that breathing which was externally paced would increase HF power compared to spontaneous breathing conditions. HF power was elevated during the paced breathing conditions in comparison to spontaneous breathing at rest and during unloaded exercise. Consequently, the hypothesis was accepted. Thus, ventilatory variables should be recorded in following studies as there may be links between ventilation and HRV indices. The previous studies used participants' freely chosen cadence when cycling, this may have influenced the HRV. The third study tested the hypothesis that cycling cadence affected HRV indices. HRV indices from 16 male participants were analysed when cycling at 40, 60, 80 and 100 revs.min-1 on an unloaded (0 Watts) and loaded (100 Watts) seated cycle ergometer. HRV indices declined as cadence was increased. Thus, the hypothesis was accepted. If HRV indices were to be calculated during subsequent experiments, both cadence and power output would have to be standardised. The first three studies provided information on the conditions which must be present to produce reliable HRV data during moderate intensity exercise. These studies also indicated that an additional means of measuring autonomic activity should be included. Study Four was designed to establish if one hypoxic exposure would influence a second exposure, if there was no effect the model could be adopted for the final experiment. This study also examined the effect of hypoxia on HRV indices at rest and during exercise. It was hypothesised that exercise and hypoxia would exert separate and additive effects on HRV indices and catecholamine concentrations. Twelve male participants rested and exercised on a loaded cycle ergometer (100 Watts) in normoxic (faction of inspired Oxygen, FIo2 0.2093) and hypoxic conditions (FIo2 0.15) on two occasions, separated by 96 hours. HRV and catecholamine concentrations were similar between the normoxic and hypoxic resting conditions. During exercise in normoxia catecholamine concentrations increased and Ln HF power was reduced, further increases in catecholamine concentrations and a reduction in Ln HF power were found during exercise in hypoxic conditions. The hypothesis was rejected for resting conditions, and accepted for the exercise conditions. It was also found that the first hypoxic exposure did not influence the HRV indices and catecholamine concentrations of the second hypoxic exposure and this model could therefore be used for the final experiment. The final study (Study Five) tested for the presence of a 'cross-adaptation' response in cold habituated humans to hypoxic exposures during rest and moderate intensity exercise. This study was designed on the basis of the information obtained from the previous four experiments and tested the hypothesis that cold habituation by repeated cold-water immersions would reduce the sympathetic activity and cardio-respiratory responses during loaded cycling (100 W) in hypoxic conditions (FIo2 0.12). Thirty-two male participants underwent six, five minute immersions in either cold (12 °C) or thermoneutral (35 °C) water over a three day period. The normoxic and hypoxic exposures were performed before and after the water immersions. It was established that cold habituation attenuated the sympathetic response to loaded exercise during an acute hypoxic exposure and reduced the number and severity of acute mountain sickness (AMS) symptoms. The study provides the first evidence of a cross-adaptation between cold habituation and hypoxic exposure in humans. This was not found in participants who performed thermoneutral water immersions. Therefore, the hypothesis was accepted. In conclusion, in four of four participants whose catecholamine concentrations were analysed and eight from 16 volunteers whose HRV was analysed, showed that cold habituation reduces the sympathetic response to an acute hypoxic stimulus during loaded cycling. However, it is not known if this cross-adaptation provides an adaptive or maladaptive response to prolonged exposure to hypoxia or altitude. Additionally, the permanence of the cross-adaptation also requires further investigation.

The current work is novel in that it investigated in vivo analysis of glucose metabolism during and following hypoxic exposure in type 2 diabetics. Using moderate levels of hypoxia, study one found that 60 min of resting hypoxic (Hy Rest) exposure reduced blood glucose concentrations in type 2 diabetics. Insulin sensitivity was also found to be significantly greater following hypoxic exposure when compared to the normoxic control. The second study showed that exercise under hypoxic (Hy Ex) conditions acutely reduced arterialised blood glucose concentrations. The total area under the curve for insulin was also significantly lower subsequent to an intravenously administered glucose load (IVGTT) in the 4 hr following Hy Ex versus normoxic exercise. The third study demonstrated that glucose disposal was acutely enhanced in exercise bouts lasting 60 and 40 min (of equal work) in hypoxia.

The reduction in O2peak at altitude is well documented. Maximal exercise in hypoxia is accelerated through a reduction in O2 supply with contributions from central and peripheral origins of fatigue. Changes in cerebral and muscle oxygenation have not been well characterised during incremental exercise in hypoxia. It is possible attainment of O2peak is driven by the oxygenation profile of these tissues whilst changes in molecular biomarkers of endothelial function could provide some insight into the mechanisms driving systemic and regional O2 delivery and vascular hypoxic sensing capabilities. The first study of this thesis examined the impact of acute hypoxia (FIO2 = 0.12) on the cerebral and muscle oxygenation response to incremental cycling exercise using NIRS (n = 14; age: 23 ± 5yr; height: 1.80 ± 0.07m; weight: 84 ± 8kg). The profiles were characterised at equivalent relative and absolute exercise intensities and molecular blood-borne markers of O2 sensing and function were measured before and immediately after maximal exercise for changes in oxidative stress (A• and 3-NT), NO metabolites (NOx, NO3•, NO2• and RSNO) and cell adhesion molecules (sICAM-1 and sVCAM-1). The key observations from this study were: 1) O2peak decreased by 22% and the magnitude of cerebral and muscle deoxygenation (↓O2Hb and ↑HHb) was greater in hypoxia, 2) the slope for the relative HHb response was similar between conditions whereas there was an accelerated slope across the absolute workloads in hypoxia implying cycling performance was driven by a premature attainment of maximal O2 extraction capacity of the muscle, 3) there was no evidence suggesting cerebral O2 metabolism was impaired in hypoxia however since SaO2 was 78 ± 4% at PPO it is possible the reduction in systemic O2 delivery could have influenced central fatigue, 4) there was a tendency for a rightward shift in the cerebral THb profile in hypoxia and although muscle THb peaked at 80% PPO in both trials, the response also tended to be lower in hypoxia, 5) there was no change in oxidative stress markers and NOx after exercise, 6) RSNO increased and NO2• decreased after maximal exercise. The decline in NO2• was attenuated in hypoxia possibly due to a blunted NO2•-HHb-NO pathway and may explain the systemic hypoperfusion response, 7) The increase in sICAM-1 and sVCAM-1 after exercise was augmented in normoxia, 8) Only when normoxia and hypoxia data was pooled was there a correlation between sVCAM-1 pre-post exercise and O2peak. Intermittent hypoxia (IH) may be used to improve the efficiency of exercise training and as a pre-acclimatisation strategy prior to high altitude ascent. The purpose of the second study was to evaluate the efficacy of a 10 day IH regime consisting of 9x 5 min daily exposures of 9.5% O2 breathing followed by equal periods of normoxia on submaximal and maximal cardiorespiratory responses to exercise in hypoxia. Additionally, cerebral and muscle oxygenation was monitored throughout incremental cycling to exhaustion and changes in NO metabolites (NO3•, NO2• and RSNO) and CAMs (sICAM-1 and sVCAM-1) were measured before and immediately after maximal exercise. The key observations from this study were: 1) a tendency for IH to reduce submaximal O2 and increase O2peak in hypoxia, 2) IH increased the muscle THb response to exercise due an increased intercept for both the muscle O2Hb and HHb in the absence of any change in slope, 4) cerebral oxygenation increased (↑O2Hb) at rest and during exercise, 4) the reduction in nitrite was attenuated in the IH group whilst resting sICAM-1 decreased and the pre-post maximal exercise increase in sICAM-1 was augmented after IH. It is concluded that exercise performance in acute hypoxia is driven by the magnitude of hypoxaemia and an accelerated rate of cerebral and muscle deoxygenation. Molecular biomarkers of endothelial function in particular, NO2• and CAMs, are also influenced by hypoxia and may contribute to the reduction in O2peak. IH may be used to improve exercise economy and O2peak in hypoxia by improving cerebral and muscle oxygenation in the absence of any change in central O2 delivery. It is possible a recalibration of mechanisms that affect NO bioactivation could have enhanced vascular hypoxic sensitivity, O2 delivery and adaptation within brain and muscle tissue which ultimately translated to an improved hypoxic exercise performance. These results give motivation for athletes and mountaineers to incorporate an IH strategy prior to athletic performance at altitude.

On sait depuis longtemps que l’exposition à l’altitude est associée à une réduction de l’aptitude aérobie. Différentes hypothèses ont été posées pour expliquer cette limitation à l’effort en hypoxie (une limitation ventilatoire ou diaphragmatique, une altération de la diffusion pulmonaire et une disconcordance entre de la perfusion et la diffusion tissulaire, etc.) mais généralement, la limitation de l’effort aérobie en hypoxie est attribuée à une diminution du transport sanguin de l’O2 (TO2) parc convection vers les muscles. Le TO2 dépend du débit cardiaque (Q) et du contenu artériel en O2 (CaO2).

Le CaO2 est diminué en altitude à cause d’une diminution de la pression partielle inspirée en O2. Cependant, le chémoréflexe hypoxique tente de contrebalancer cet effet en élevant la ventilation et en diminuant la pression alvéolaire en CO2 afin de maintenir la pression alvéolaire en O2 constante. De plus, avec l’acclimatation, le rein produit de l’érythropoïétine permettant au taux d’hémoglobine d’augmenter. Ces deux principales adaptations à l’altitude ramènent le CaO2 à sa valeur de base du niveau de la mer en 2 à 3 semaines passées à 5000 m d’altitude mais sans amélioration de l’aptitude à l’effort aérobie.

L’exposition à l’altitude est aussi associée à une diminution du Q maximal. Les mécanismes à l’origine de cette limitation du Q maximal restent, à l’heure actuelle, incompris. Les principales explications évoquées sont, une diminution de la réserve chronotrope, une diminution de la commande nerveuse centrale vers le cœur ou une diminution de la demande périphérique. Récemment, des études sur des sujets sains en hypoxie suggérèrent qu’au moins une partie de la limitation du Q maximal à l’effort est liée à une élévation de la postcharge ventriculaire droite suite à l’hypertension pulmonaire induite par l’hypoxie. C’est cette hypothèse que nous avons voulu vérifier dans une première étude.

Nous avons étudié l’effet d’une inhibition de l’hypertension pulmonaire d’altitude par le sildénafil, un inhibiteur de la phosphodiestrérase-5, chez des sujets sains, en normoxie, en hypoxie aiguë et en hypoxie chronique. Les résultats de cette étude ont confirmé l’effet vasodilatateur pulmonaire du sildénafil et une augmentation de la VO2max en hypoxie aiguë. Cependant, la prise de ce dernier était couplée à une amélioration de l’oxygénation, si bien que l’élévation de la performance aérobie observée en hypoxie aiguë sous sildénafil ne pouvait être entièrement attribuée à une réduction de l’hypertension pulmonaire.

Nous conclurent que cette amélioration de la performance était probablement d’avantage liée à une amélioration de l'oxygénation qu’à un effet vasodilatateur pulmonaire.

Les résultats équivoques obtenus lors de cette première étude nous ont incité à tester les effets d’une amélioration de l’oxygénation sur la performance aérobie en haute altitude. Pour ce faire, quinze sujets sains ont été testés au niveau de la mer et après acclimatation à 4700 m d’altitude soit sous placebo, soit sous acétazolamide, un inhibiteur de l’anhydrase carbonique augmentant l’oxygénation par stimulation ventilatoire en réponse à une acidose métabolique. La prise d’acétazolamide n’eut aucun effet sur l’hémodynamique pulmonaire et sur la VO2max et la charge maximale. Nous avons toutefois observé qu’une amélioration de l’oxygénation durant l’effort retarde l’apparition du seuil ventilatoire améliorant ainsi la phase aérobie de l’effort. Cette étude confirme donc qu’une élévation du CaO2 permet une amélioration de l’aptitude aérobie.

Finalement, la dernière étude a pour but d’étudier les effets isolés d’une vasodilatation pulmonaire sur la performance aérobie en altitude. Les résultats d’une étude préliminaire montrent que l’inhibition de la vasoconstriction hypoxique par un agent pharmacologique antagoniste des récepteurs de l’endothéline ETA et ETB, le bosentan, permet une élévation de l’aptitude aérobie en hypoxie aiguë, sans effets sur l’oxygénation, confirmant ainsi notre hypothèse initiale qu’une postcharge ventriculaire droite augmentée en hypoxie peut contribuer à une limitation de l’aptitude à l’effort aérobie en hypoxie.

Conclusions :

L’ensemble de nos résultats suggère que l’aptitude aérobie en altitude est déterminée par le transport d’O2 qui peut être augmenté par manipulation pharmaceutique du débit ventriculaire droit maximal après inhibition de la vasoconstriction pulmonaire hypoxique (bosentan), amélioration de l’oxémie (acétazolamide) ou des deux (sildénafil).

Agrégation de l'enseignement supérieur en kinésithérapie et réadaptation
info:eu-repo/semantics/nonPublished

The purpose of the current study was to test the hypothesis that chronic hypoxia associated with sleep-disordered breathing relates to abnormal Nitric Oxide (NO) production and vascular endothelial growth factor (VEGF) expression patterns that contribute to aberrancy of specific determinates of cardiovascular and cardiopulmonary function before, during, and after graded exercise. These patterns may further reflect pathologic alteration of signaling within the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt-1) transduction network. To this end, 7 medically diagnosed OSA patients (3 male, 4 female), mean age 48 years and 7 apparently healthy control subjects (3 male, 4 female), mean age 42 years, underwent baseline venous blood draws and maximal bicycle ergometry. Mononuclear cells isolated from peripheral blood were utilized as reporter cells for measurement of VEGF, Akt-1, hypoxia inducible factor-1 alpha (HIF-1 alpha), and vascular endothelial growth factor receptor-2 (VEGFR2) gene expression by redundant oligonucleotide DNA microarray and real-time PCR technologies. Circulating angiogenic progenitor cells expressing VEGFR2 were profiled by flow cytometry. Plasma and serum concentrations of VEGF, nitrates/nitrites, catecholamines, and dopamine were measured by enzyme-linked immunosorbent assay (ELISA) and high performance liquid chromatography (HPLC). Arterial blood pressure, cardiac output, oxygen consumption and total peripheral resistance were determined at Baseline, 100W, and peak ergometric stress by standard techniques. There were no apparent differences (p < .05) observed in biochemical markers relating to vascular function and adaptation including, serum nitrates/nitrites, norepinephrine, dopamine, and plasma VEGF. No differences were found relative to cardiac output, stroke volume, cardiopulmonary or myocardial oxygen consumption, expired ventilation, heart rate, arteriovenous oxygen difference, total peripheral resistance, and mean arterial pressure. Due to methodological issues related to the redundant oligonucleotide DNA microarray and real-time PCR gene expression analyses, results of these experiments were uninterpretable. Thus, the research hypothesis was rejected. Conversely, significant (p < .05) differences were observed in waist: hip ratios, recovery: peak systolic blood pressure ratio at 1 minute post-exercise and %VEGFR2 expression. OSA was associated with elevations in both waist: hip ratios and recovery: peak systolic blood pressure ratio at 1 minute post-exercise as well as significant depression of %VEGFR2 profiles. Moreover, significant negative correlations were found regarding waist: hip ratios and %VEGFR2 expression (r = -.69;p =.005) and recovery: peak systolic blood pressure ratio at 1 minute post-exercise and %VEGFR2 expression (r = -.65;p =.01). These findings did not provide evidence that NO-dependent vasoactive mechanisms are suppressed nor did they support the supposition that angiogenic mechanisms are pathologically activated in sleep-disordered breathing.
Ph. D.

Ce travail a été consacré à l’étude non invasive de la circulation pulmonaire normale par mise en œuvre de l’échocardiographie Doppler.

En intégrant les mesures obtenues dans une approche physiopathologique, et en exploitant les nouvelles possibilités d’échocardiographes portables, techniquement performants, nous avons analysé les effets d’un inhibiteur de la phosphodiestérase-5 et d’une prostacycline, pour tenter d’en identifier d’éventuels effets introtropes intrinsèques, nous avons exploré le concept de réserve vasculaire pulmonaire comme facteur limitant de l’aptitude aérobie et indice potentiel d’une atteinte vasculaire pulmonaire précoce, et obtenu des résultats préliminaires permettant d’identifier une hypertension artérielle pulmonaire (HTAP) latente. Nos principaux résultats peuvent être résumés comme suit :

1. Chez le sujet sain, en normoxie ou dans un modèle expérimental d’HTAP induite par l’inhalation d’un mélange gazeux hypoxique, le sildenafil per os ou l’epoprostenol par voie intraveineuse, à des doses utilisées en clinique pour le traitement de l’HTAP, améliorent les indices de la fonction ventriculaire droite en proportion de leurs effets vasodilatatoires pulmonaires, sans effets inotropes intrinsèques détectables.

2. La consommation d’oxygène maximale du sujet sain augmente en raison directe de son volume capillaire pulmonaire (calculé à partir de sa capacité de diffusion pour l’oxyde nitrique et le monoxyde de carbone) et en raison inverse de sa résistance vasculaire pulmonaire, non seulement en altitude, mais aussi au niveau de la mer. Ce résultat suggère qu’une plus grande réserve vasculaire pulmonaire est propice aux efforts aérobiques intenses, probablement par moindre postcharge ventriculaire droite.

3. Des mesures réalisées chez un petit nombre de sujets suggèrent que la distensibilité vasculaire pulmonaire, calculée à partir d’une relation débit-pression vasculaire pulmonaire, est typiquement réduite chez des porteurs asymptomatiques de la mutation BMPR2, qui est actuellement le facteur de risque le plus élevé connu de l’HTAP. La mutation BMPR2 pourrait aussi être associée à une réactivité vasculaire pulmonaire accrue à l’hypoxie.

Nos résultats suggèrent indirectement que l’échocardiographie Doppler, de repos ou de stress, pourrait être davantage développée dans la mise au point de patients à risque d’HTAP./

Novel advances in echocardiography offer the opportunity to reliably characterize pulmonary circulation in terms of pressure-flow relationship, and to better understand the coupling of right ventricular (RV) function with normal and abnormal pulmonary hemodynamics. Moreover, when combined with the measurement of pulmonary capillary blood volume, this renewed methodological approach may help to understand the concept of pulmonary vascular reserve as a limiting factor of exercise capacity and potential sensitive marker of early vascular disease.

In the present work we used a model of hypoxic pulmonary vasoconstriction to analyse the effects of two targeted therapies of pulmonary arterial hypertension (PAH) on the RV function. We showed that the beneficial effects of these drugs are mainly driven by a decrease in RV afterload and not an enhanced myocardial inotropic state. Whether this is transposable to abnormal RV-arterial coupling in PAH patients remains to be investigated.

Echocardiography may be useful to explore the pulmonary vascular reserve as an important limiting factor of exercise capacity. We showed that a higher pulmonary vascular reserve, defined by a decreased PVR and increased lung diffusing capacity, allows for an improved aerobic exercise capacity (as assessed by a higher peak oxygen consumption), at a lower ventilatory cost, at sea level and at high altitude.

Stress echocardiography may detect an abnormal pulmonary vasoreactivity. We showed that asymptomatic relatives of patients suffering from idiopathic pulmonary arterial hypertension, and who carry a bone morphogenetic protein receptor type 2 mutation (BMPR2) present with a decreased pulmonary vascular distensibility and an enhanced pulmonary vasoreactivity to hypoxia, which are identifiable by echocardiography examination. However, the predictive value of these findings is not known.

Thus echocardiography may represent, in experienced and dedicated hands, a noninvasive, safe, widely available, applicable at the bed-side as well as in extreme environment (e.g. high altitudes), less expensive alternative for the evaluation of the pulmonary circulation, either by the interrogation of pressure-flow relationship (stress echocardiography), by the investigation of the right ventricle global and regional function in relation to its afterload (standard and Tissue Doppler Imaging), or by a combined approach with the measurement of lung diffusing capacity (DLNO / DLCO) to assess the pulmonary vascular reserve.

The present data are encouraging for further development and implementation of echocardiography for the detection, but also the diagnosis and follow-up of patients with pulmonary hypertension.

Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished

Orientador: Antonio Carlos de Moraes
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Educação Física
Made available in DSpace on 2018-08-21T22:00:45Z (GMT). No. of bitstreams: 1 Smirmaul_BrunodePaulaCaraca_M.pdf: 4243812 bytes, checksum: 6a170352ba2b6b469396a6dd7c5d13f5 (MD5) Previous issue date: 2013
Resumo: Introdução: Apesar de ser uma substância extensivamente estudada no âmbito do desempenho físico, a cafeína e seus efeitos no desempenho em altitude (hipóxia) foram estudados em apenas 2 investigações científicas (Berglund & Hemmingsson 1982; Fulco et al 1994), sugerindo que esta tem seus efeitos potencializados nesse ambiente. As únicas variáveis analisadas foram percepção de esforço e parâmetros cardiorrespiratórios. Porém, um dos mecanismos de ação sugeridos da cafeína é no sistema neuromuscular que, em hipóxia, sofre com uma mais rápida ocorrência de fadiga. Objetivo: Investigar o efeito da cafeína no desempenho aeróbio em hipóxia nos parâmetros psicofisiológicos, em particular seus efeitos na fadiga periférica e central. Métodos: Sete sujeitos (29 ± 6 anos, 179 ± 8 cm, 75 ± 8 kg, VO2máx 51 ± 5 ml.kg-1) participaram desse estudo duplo-cego e randomizado. Primeiro realizaram um teste incremental máximo em hipóxia (FIO2 = 0,15) para determinar a potência pico. A segunda e terceira visita consistiu em um período fixo de 6 min de exercício, seguido de um teste constante até a exaustão, ambos a _80% da potência pico e em hipóxia. Lactato, SpO2, percepção de esforço, frequência cardíaca, e fadiga periférica e central foram mensuradas. Resultados: Durante o teste incremental, a potência pico alcançada foi de 275 ± 38 W, com valores finais de percepção de esforço, lactato, frequência cardíaca e SpO2 de 18 ± 1, 13 ± 2 mmol/l, 179 ± 10 bpm, e 81 ± 5%, respectivamente. Tempo até a exaustão foi significativamente maior (11,8%) na condição cafeína (402 ± 137 s) comparado à condição placebo (356 ± 112 s) (P = 0,016). Tempos individuais foram maiores com cafeína em 6 dos 7 sujeitos. Variação intra-sujeito foi de -5 a 23% (-10 a 74 s). Cafeína teve um impacto significativo na subescala de humor fadiga, apresentando menores valores, enquanto a subescala vigor apresentou tendência a ser maior nessa condição. A percepção de esforço apresentou menores valores para o grupo cafeína durante o teste até exaustão. Tanto para o período de 6 minutos como durante o teste de tempo até a exaustão, a frequência cardíaca foi maior para o grupo cafeína. Enquanto SpO2 foi menor para o grupo cafeína apenas durante o período de 6 minutos, os valores de lactato não diferiram entre os grupos, mas apresentaram tendência a maiores valores na condição cafeína. Os valores de contração voluntária máxima apresentaram declínio significativo, com maior queda para o grupo cafeína. Já os valores de ativação voluntária e estímulos duplos, apesar de decrescerem, não foram diferentes entre as condições. Por fim, todos os parâmetros de oxigenação não diferiram entre as condições. Conclusão: O efeito ergogênico da cafeína em altitude ocorreu concomitantemente a alterações no estado de humor, percepção de esforço, sinais eletromiográficos, frequência cardíaca e contração voluntária máxima
Abstract: Introduction: Despite being a substance extensively studied in the physical performance scope, caffeine and its effects on performance in altitude (hypoxia) have been studied only in 2 scientific investigations (Berglund & Hemmingsson 1982; Fulco et al 1994), and it is suggested that is has greater effects in this environment. The variables analyzed were only perception of effort and cardiorespiratory parameters. However, one of the suggested caffeine's mechanisms of action is upon the neuromuscular system that, in hypoxia, presents a faster development of fatigue. Aim: Study the effects of caffeine during aerobic performance in hypoxia in the psychophysiological parameters, in particular its effects on peripheral and central fatigue. Methods: Seven subjects (29 ± 6 years, 179 ± 8 cm, 75 ± 8 kg, VO2max 51 ± 5 ml.kg-1) participated in this randomized double-blind study. First it was performed a maximal incremental test in hypoxia (FIO2 = 0.15) to determine peak power output. The second and third visits consisted of a fixed period of 6 min of exercise, followed by a time to exhaustion test, both at _80% of peak power output and in hypoxia. Lactate, SpO2, perception of effort, heart rate, and peripheral and central fatigue were measured. Results: During the incremental test, peak power output reached was 275 ± 38 W, with end-values of perception of effort, lactate, heart rate and SpO2 of 18 ± 1, 13 ± 2 mmol/l, 179 ± 10 bpm, and 81 ± 5%, respectively. Time to exhaustion was significantly longer (11.8%) with caffeine (402 ± 137 s) compared to placebo (356 ± 112 s) (P = 0.016). Individual times were longer with caffeine in 6 out of 7 subjects. Intra-subject variability was from -5 to 23% (-10 to 74s). Caffeine had a significant impact on the mood subscale fatigue, presenting lower values, while the subscale vigor presented a trend to be higher in this condition. Perception of effort presented lower values in the caffeine condition during time to exhaustion test. Both to the fixed period of 6 minutes and to the time to exhaustion test, heart rate was higher in the caffeine condition. While SpO2 was lower with caffeine only during the fixed period of 6 minutes, lactates values did not differ between groups, but presented a trend to be higher during the caffeine condition. Values of maximal voluntary contraction showed a significant reduction, with greater reduction in the caffeine condition. However, voluntary activation and doublet values, despite decreasing, were not different between conditions. Finally, all the brain oxygenation parameters did not differ between conditions. Conclusion: The ergogenic effect of caffeine at altitude occurred concomitantly with alterations in mood state, perception of effort, electromyographic signals, heart rate and maximal voluntary contraction
Mestrado
Biodinamica do Movimento e Esporte
Mestre em Educação Física

This thesis examined the impact of oxygen (O2) availability on prefrontal cortex and muscle tissue oxygenation during repeated-sprint exercise (RSE) in men and women. Men and women matched for initial-sprint mechanical work performed during ten, 10-s sprints (30s of rest) in normoxia (21% FIO2) and acute hypoxia (13% FIO2). Mechanical work and arterial O2-saturation (SPO2) were obtained for every sprint. Oxy- and deoxygenated haemoglobin concentrations (O2Hb, HHb) were obtained via near-infrared spectroscopy. Hypoxia elicited lower SPO2 and work (14.8% & 7.4%, P < 0.05), larger (45.1%, P < 0.05) and earlier reductions in cortical oxygenation, and no differences between sexes. Cortical de-oxygenation and work decrement were strongly correlated (R2=0.85, P < 0.05). Muscle de-oxygenation was greater in men than women (67.3%, P < 0.05). These results show that O2 availability influences cortical oxygenation and performance equally in men and women, and suggest a more efficient muscle O2 uptake in women.
ix, 108 leaves : ill. ; 29 cm

The current understanding of lactate metabolism in fish is based almost entirely on interpretation of concentration measurements that cannot be used to infer changes in flux. Moreover, the transporters regulating these fluxes have never been characterized in rainbow trout. My goals were: (1) to quantify lactate fluxes in rainbow trout under normoxic resting conditions, during acute hypoxia, and exercise by continuous infusion of [U-14C] lactate; (2) to determine lactate uptake capacity of trout tissues by infusing exogenous lactate in fish rest and during graded exercise, and (3) to clone monocarboxylate transporters (MCTs) and determine the effects of exhausting exercise on their expression. Such information could prove important to understand the mechanisms underlying the classic “lactate retention” seen in trout white muscle after intense exercise. In normoxic resting fish, the rates of appearance (Ra) and disappearance (Rd) of lactate were always matched (~18 to 13 µmol kg-1 min-1), thereby maintaining a low baseline blood lactate concentration (~0.8 mM). In hypoxic fish, Ra lactate increased from baseline to 36.5 µmol kg-1 min-1, and was accompanied by an unexpected 52% increase in Rd reaching 30.3 µmol kg-1 min-1, accounting for a rise in blood lactate to 8.9 mM. In exercising fish, lactate flux was stimulated > 2.4 body lengths per second (BL s-1). As the fish reached critical swimming speed (Ucrit), Ra lactate was more stimulated (+67% to 40.4 μmol kg-1 min-1) than Rd (+41% to 34.7 μmol kg-1 min-1), causing an increase in blood lactate to 5.1mM. Fish infused with exogenous lactate stimulated Rd lactate by 300% (14 to 56 μmol kg-1 min-1) during graded exercise, whereas the Rd in resting fish increased by only 90% (21 to 40 µmol kg-1 min-1). Four MCT isoforms were partially cloned and characterized in rainbow trout: MCT1b was the most abundant in heart, and red muscle, but poorly expressed in gill and brain where MCT1a and MCT2 were prevalent. MCT4 was more expressed in the heart. Transcript levels of MCT2 (+260%; brain), MCT1a (+90%; heart) and MCT1b (+50%; heart) were stimulated by exhausting exercise. This study shows that: (i) the increase in Rd lactate plays a strategic role in reducing the lactate load imposed on the circulation. Without this response, blood lactate accumulation would double; (ii) a high capacity for lactate disposal in rainbow trout tissues is elicited by the increased blood-to-tissue lactate gradient when extra lactate is administered; and (iii) rainbow trout may be unable to release large lactate loads rapidly from white muscle after exhausting exercise (lactate retention) because they poorly express MCT4 in white muscle and fail to upregulate its expression during exercise.

The physiological response to environmental hypoxia encountered at high altitude has a wide range of cardiovascular and pulmonary effects. The insertion allele of the angiotensin converting enzyme (ACE) gene polymorphism has been found to be more prevalent in endurance athletes and is associated with beneficial anabolic and functional responses in muscle. Furthermore, the insertion allele of this functional genetic polymorphism has been associated with enhanced physical performance at altitude, as defined by the successful ascent of peaks over 4800 metres. This thesis examines the cardiopulmonary responses during exercise and hypoxia in order to elucidate any genotype dependent differences in cardiopulmonary response that could explain this observation. The main body of this work was carried out between August 1999 and September 2001. The studies involved 60 healthy subjects performing a maximal cardiopulmonary exercise test to determine ventilatory threshold (VT). At the second visit the subjects underwent a second set of steady state exercise tests, performed at 50% of the work rate attained at VT, under normoxic and hypoxic conditions (FiO2 12.5%). Metabolic and ventilatory measurements were made during tests and the changes between normoxic and hypoxic response during rest and exercise were analysed. A second smaller study examined cardiac output response during hypoxia and exercise using bioimpedance cardiography. These studies were performed simultaneously with the cardiopulmonary exercise tests and included 31 subjects. Similar analyses were performed on cardiac output variables between normoxia and hypoxia. The repeatability of the steady state cardiopulmonary exercise experimental protocol was verified by repeat testing and analyses. Bioimpedance cardiography measurements were validated against simultaneous measurements during pulmonary catheter studies and thermodilution cardiac output measurement. The results of the tests and the comparison of response demonstrated a larger increase in ventilation during exercise from normoxia to hypoxia in the insertion homozygous group. This was accompanied by a genotype dependent decrease in end-tidal carbon dioxide, suggesting a higher alveolar ventilation. There was no increase in oxygen saturations in the insertion homozygous group, which may have been due to the technical limitations of the oximeters. The cardiac output studies did not reveal any significant difference between genotype. The ventilatory study has demonstrated a response that may contribute to enhanced performance during prolonged hypoxic exposure, as experienced at high altitude.