La dystrophie FacioScapuloHumérale (FSHD), décrite pour la première fois en 1885 par Landouzy Dejerine, est la première dystrophie musculaire de l’adulte en France affectant entre 4000 et 5000 personnes. La destruction progressive des fibres musculaires entraîne une atrophie et une faiblesse musculaires s’aggravant progressivement, avec cependant une grande variabilité intra-familiale du degré des atteintes. Une caractéristique de l’atteinte musculaire est généralement son asymétrie. Les premières manifestations concernent souvent les muscles du visage, les muscles de l’omoplate et des muscles perihuméraux. En progressant la pathologie va toucher d’autres territoires musculaires. Dans environ 10 à 15 % des cas, à un stade évolué, les patients sont contraints d'utiliser un fauteuil roulant. En dépit d’avancées majeures dans la compréhension du locus morbide, les mécanismes exacts responsables des défauts musculaires de la FSHD ne sont toujours pas compris et il n’existe aucune thérapie. Toutefois, il existe de plus en plus de données qui permettent une implication probable du stress oxydant dans cette pathologie. L’hypothèse selon laquelle les réponses antioxydantes sont altérées dans la FSHD s’appuie sur des dérégulations d’enzymes impliqués dans le stress oxydant. Une étude prospective réalisée sur des patients FSHD et des volontaires sains nous a ainsi permis de mettre en évidence une corrélation entre le stress oxydant systémique et musculaire et leurs déficits fonctionnels musculaires. Ces données nous ont conduit à la mise en place d’un essai clinique randomisé, contrôlé, en double aveugle contre placébo, visant à évaluer les effets d’une supplémentation en antioxydants chez 54 patients atteints de FSHD pendant 17 semaines. Cet essai a ainsi permis de montrer une augmentation significative de la force et l’endurance des quadriceps corrélée à une diminution du stress oxydant et une augmentation des défenses antioxydantes chez les patients atteints de FSHD. De nombreuses caractéristiques de la FSHD pourraient être causées et/ou exacerbées par des perturbations de la production des espèces radicalaires ou une réponse non adaptée à cette production. Aussi le premier objectif de ma thèse est de mener une étude comparative des profils d’oxygénation par spectroscopie dans le proche infrarouge de patients atteints de FSHD et sains. Le second objectif est d’évaluer l’effet de la supplémentation en antioxydant sur le volume des quadriceps par IRM et leur qualité musculaire déterminée par le ratio Force/Volume musculaire du quadriceps et d’évaluer les corrélations entre ces variables, la force et le stress oxydant. Les données obtenues ont permis de montrer une réduction de la capacité oxydative lors d’une contraction isométrique volontaire des quadriceps et ont permis d’étudier l’effet de la supplémentation sur les volumes et la qualité musculaire des quadriceps. Ces augmentations sont associées non seulement à une augmentation de la force des quadriceps mais aussi à une diminution du stress oxydant et une augmentation des défenses antioxydantes. L’ensemble de ces données montrent que le stress oxydant pourrait jouer un rôle important dans la FSHD et qu’une approche antioxydante semble adaptée à cette pathologie. Des analyses plus fines sur l’action des espèces réactives de l’oxygène (ROS) et leurs sources pourraient contribuer à une meilleure compréhension des bases physiopathologiques de la FSHD. / Facioscapulohumeral muscular dystrophy (FSHD), first described in 1885 by Landouzy Dejerine, is the most common inherited skeletal muscle disease of adult life affecting 4000 to 5000 persons in France. Progressive evolution of the disease leads to progressive weakness and atrophy of muscle fibers associated to a wide variability. The pattern of muscle weakness is often asymmetrical and the rate and extent of progression may vary considerably with sudden periods of unexplained rapid disease progression. This muscle disorder is characterized by progressive muscle weakness, beginning with facial muscles and the shoulder girdle, followed by the pelvic girdle and the muscles of the lower extremities. In 10 to 15% of cases, patients need to use a wheelchair. Despite major progress in the understanding of the genetic basis of FSHD, the exact mechanisms that lead to FSHD defects are not completely understood and no curative treatment is available. However, there is growing evidence that oxidative stress may contribute to FSHD pathology. The hypothesis that oxidative stress responses might be specifically altered in FSHD is supported by the deregulation of enzymes involved in oxidative stress.A prospective study realized with FSHD patients and healthy subjects unrevealed the correlation between systemic and muscular oxidative stress and functional muscle defects. Based on these data, we organized a randomized, double-blind, placebo-controlled pilot clinical trial in order to evaluate the effects of 17 weeks antioxidant supplementation in 54 FSHD patients. This clinical trial demonstrates a significant increase in muscle force and quadriceps endurance correlated to a decrease in oxidative stress and an increase in antioxidant defense in FSHD patientsFurthermore, many FSHD features may be caused or exacerbated by perturbations in the production of free radicals or inappropriate response to such stressors. Therefore the first objective was planned to investigate muscle oxygenation patterns during and after a MVCQ by near-infrared diffuse optical spectroscopy (NIRS). The second objective is to evaluate the effect of antioxidant supplementation on quadriceps volumes by IRM and determine the muscle quality using Strength/ Volume ratio of quadriceps muscles and correlate this variables with force and oxidative stress parameters.The major findings of this study show a significant decrease in oxidative capacity during voluntary isometric contraction in quadriceps and demonstrate the effect of supplementation on muscle volume and quality. Indeed, vitamin E, vitamin C, zinc and selenium supplementation improves muscle volume and quality of both quadriceps by enhancing the antioxidant defences and reducing oxidative stress.This increase are associated to increase in strength and decrease in oxidative stress and increase in antioxidant defences. Taken together, we show that oxidative stress plays an important role in FSHD and that an anti-oxidant strategy adapted to the FSHD-specific “oxidative stress” may be a relevant therapeutic approach for these patients. Further analyses of ROS production and sources could contribute to a better understanding of the pathophysiological mechanisms implicated in FSHD.

Master of Science / Department of Kinesiology / Thomas J. Barstow / Dietary nitrate supplementation via beetroot juice (BR) has been shown to have positive effects on mitochondrial and muscle efficiency during large muscle mass exercise in humans, and more recently on locomotory muscle blood flow [Q-dot] in rats. To date, an integrated measure of these effects has not been performed in humans. Therefore, we assessed the influence of BR on [Q-dot] and muscle oxygenation characteristics during moderate and severe intensity handgrip exercise. Seven healthy men (age: 25 ± 3 yrs; height: 179 ± 4 cm; weight: 82 ± 9 kg) completed four constant-power exercise tests randomly assigned to condition (BR or placebo (PL)) and intensity (moderate (40% peak) or severe (85% peak)). Resting mean arterial pressure was significantly lower after BR compared to PL (79.3 ± 5.8 vs 86.8 ± 6.7 mmHg; p < 0.01). All subjects were able to sustain 10 min of exercise at moderate intensity in both conditions. BR had no significant effect on exercise tolerance during severe (342 ± 83 vs 382 ± 138 s, p = 0.382). Brachial artery [Q-dot] was not significantly different after BR at rest or any time during exercise in either intensity. Deoxygenated-[hemoglobin + myoglobin] was elevated at min 2 & 3 for moderate (p < 0.05) and throughout severe exercise (p = 0.03) after BR. The estimated metabolic cost ([V-dot]O₂) was not significantly different during either intensity after BR. These findings support the notion that an acute dose of BR may be valuable to reduce blood pressure in young adults, but revealed that it does not augment [Q-dot] or [V-dot]O₂ during small muscle mass handgrip exercise.

Hyperbaric Oxygenation Therapy (HBOT) has a successive history for treating very specific groups of physical conditions. Research by Neubauer and colleagues states that HBOT's ability to increase cerebral metabolism in the brain regenerates dormant neural tissue (Neubauer, Gottlieb, & Pevsner 1994). According to this research, the increase of cerebral metabolism levels restores mental capacity from the neurological insult. Despite promise, uncertainty exists as to whether this is a viable treatment option for people suffering from neural damage. The research results for this experiment will examine the effect of HBOT on cerebral metabolism levels in adults and pediatrics with chronic neurological problems. Fifty individuals diagnosed as having a neurological impairment whom met criteria for the study were analyzed from an archival data set. Criterion required chronic impairment, baseline SPECT, followed by HBOT exposures, and a post SPECT scan. Statistical analyses consisted of a Pearson correlation that examined pre-metabolism rates with total change, a Pearson correlation that examined total change and number of treatments, and a one way ANOVA analysis that examined cerebral metabolism change in patients under 18 and over 18. Results indicated change

In der Neonatologie ist die Verabreichung von Erythrozytenkonzentrat (EK) eine der häufigsten therapeutischen Maßnahmen. Ursachen dafür sind die Frühgeborenen-anämie und die iatrogen durch diagnostische Blutentnahmen hervorgerufene sekundäre Anämie. Obwohl ca. 80% der Frühgeborenen während des postnatalen stationären Aufenthaltes EK erhalten, gibt es noch immer keine einheitlichen Richtlinien zur Bluttransfusion bei Frühgeborenen. In der vorliegenden Studie sollte der Effekt einer EK-Gabe mit Hilfe der Messung der cerebralen und peripheren Gewebsoxygenierung (crSO2 und prSO2) erfasst werden. Und es wurde der Annahme nachgegangen, dass in der Neonatologie Subgruppen existieren, welche unterschiedlich von einer EK-Transfusion profitieren. Im Rahmen dieser Promotionsarbeit wurden Frühgeborene der neonatologischen Abteilung der Universitätsklinik und Poliklinik für Kinder- und Jugendmedizin Leipzig prospektiv analysiert. Es konnte gezeigt werden, dass bei allen untersuchten Patienten sowohl die cerebrale als auch die periphere Gewebsoxygenierung unter EK-Transfusion ansteigen und auch nach einem Intervall von 24 Stunden noch auf diesem gesteigerten Niveau konstant bleiben. Zudem konnte nachgewiesen werden, dass Kinder mit niedrigen crSO2-Ausgangswerten vor Transfusion mehr Sauerstoffsättigungsabfälle unter 80% (SaO2<80%) aufweisen. Nach Transfusion ist bei diesen Patienten zusätzlich ein stärkerer Rückgang der Anzahl der SaO2<80% zu beobachten. Somit ist die Gewebsoxygenierung möglicherweise ein sinnvoller Parameter für die Indikation zur EK-Transfusion, welcher bei der Erarbeitung neuer Transfusionsricht-linien in der Neonatologie mit einbezogen werden sollte.

When O2 uptake at the lung is used to characterise the oxidative metabolic response to increased contractile activity ( O2 kinetics) in exercising muscle, the O2 profile reflects the combined influence of all involved muscle fibres. Consequently, during high-intensity exercise that mandates activation of fibres with considerable metabolic diversity (e.g., both principal fibre types), response characteristics specific to discrete segments of the recruited pool cannot be determined. The purpose of this thesis was to identify fibre-type-specific effects of conditions that might impact O2 delivery and/or motor unit recruitment patterns on O2 kinetics by using two models that increase fibre recruitment homogeneity during exercise transitions. In four experiments, subjects initiated high-intensity exercise from a moderate baseline (i.e., performed ‘work-to-work’ transitions; M→H) to target higher-order fibres, and in two experiments, subjects cycled at extremely slow and fast pedal rates to skew recruitment toward slow- and fast-twitch fibres, respectively. At mid-range contraction frequency, O2 kinetics (as indicated by the primary time constant, τp) was slower for M→H compared to unloaded-to-high-intensity transitions (U→H) (e.g., 42 v. 33 s; Ch 4) and this slowing was ~50% greater for M→H in a supine body position (decreased oxygenation; Ch 6). Slower kinetics was also present for U→H cycling at fast compared to slow pedal rates (τp, 48 v. 31 s; Ch 8). Conversely, M→H slowing relative to U→H was absent at extreme cadences (36 v. 31 s and 53 v. 48 s for slow and fast, respectively; Ch 7). After ‘priming’ (increased oxygenation), τp was reduced for U→H after fast-cadence priming only (Ch 8) and for M→H in the supine position (Ch 6), but unaffected for upright cycle and prone knee-extension M→H, for which priming reduced the O2 slow component and delayed-onset fibre activation (as indicated by iEMG; Chs 4 and 5). These results provide evidence in exercising humans that high-order fibres possess innately slow O2 kinetics and are acutely susceptible to interventions that might alter O2 delivery to muscle.

PROBLEM: Expanding knowledge of how the brain responds to various exercise types may allow for investigation and development of individualized methods of concussion management. PURPOSE: Identify differences in cerebral oxygenation recovery following bouts of maximal anaerobic, resistance and aerobic exercise. METHODS: Twenty-eight active adults were recruited, each partaking in two sessions. At the first, anthropometric measures and leg press 1-RM were determined. During the second session, cerebral oxygenation and ventilatory gas exchange variables were recorded while participants completed maximal anaerobic, resistance, and aerobic tests, and for 15-minutes of recovery. RESULTS: Anaerobic (637.41s ± 330.42s) and aerobic (689.29s ± 311.05s) exercise resulted in longer durations of time to return to baseline compared to resistance (363.07s ± 366.34s). CONCLUSION: Anaerobic and aerobic exercise taking longer than resistance to return to baseline indicates prolonged activity. Expecting equivalent outcomes as concussion management tools from differing exercise methods may be misguided and requires additional research. / February 2017

This study examined the effects of rapid and uncompensable core temperature (Tc) acquisition on cerebral oxygenation and haemodynamics, cerebral neural function, decision-making, and rate and magnitude salivary cortisol appearance. Fourteen male subjects (mean age, 33.6 ± 12.1 years) performed an incremental treadmill exercise test to a termination criterion in a control session (CON) and an experimental session (PPE). The incremental treadmill exercise test protocol included an initial 5-minute stage at 3.5 mph and a 0% grade, the second stage was 5-minutes at 3.5 mph at 4% grade, the third stage was 50-minutes at 3.5 mph and an 8% grade, and the final stage was 1-hour at 3.5 mph and a 12% grade. The Instrumentation included a near-infrared spectroscopy (NIRS) monitor, MUSE EEG monitoring system, Equivital integrated physiological monitoring system, Tc capsules, and salivary cortisol oral swabs and ELISA kit for salivary analysis. Important physiological results were significant differences in the physiological strain index (PSI) at all common points of measurement. Important cerebral oxygenation and haemodynamics results were a plateau in left-side prefrontal cortex (PFC) HbO2 and tHb at roughly Tc 38°C in both CON and PPE, 80% of TTT in CON, and 60% of TTT in PPE. Additionally, there was higher left-side PFC activation during PPE as indicated by a significant decrease in TSI % from start to end of exercise and double the decrease in TSI % per minute in PPE when compared to CON. There were no significant differences during the CON session. An analysis of frontal theta EEG power results showed a significant decrease when comparing pre- and post-exercise values during a Go/No-go test in PPE (F(1,13) = 6.069, p ≤ 0.05)). There was also a significant difference when evaluating incorrect responses between pre- and post-exercise values in PPE (F(1,13) = 12.785, p ≤ 0.01)); these differences were not observed during CON. There was also a difference in the rate of cortisol appearance (CON = 0.002 µg dL-1 min-1; PPE = 0.018 µg dL-1 min-1). In the PPE condition, mean cortisol values between start of exercise and the measurement point associated with Tc 38°C and between the start and end of exercise during PPE were significantly different (F(1,13) = 22.71, p ≤ 0.01). Lastly, there was a significant difference between magnitude of cortisol values at the termination between CON and PPE. These data suggest that rapid and uncompensable Tc acquisition during PPE caused an altered cerebral oxygenation and haemodynamic response in the left-side PFC when compared to CON. The left PFC could be working harder to prevent fatigue in PPE. This could have implications for cognitive processes during and/or following exercise in the heat while wearing PPE. These data also suggest rapid and uncompensable Tc acquisition results in decreased cognitive control. This could have implications for individuals whose occupation requires PPE and critical decision making while experiencing rapid Tc heat storage. Lastly, these results show a difference between PPE and CON in regards to rate and magnitude of salivary cortisol appearance, potentially affecting individuals chronically exposed to acute heat stress. Increased acute cortisol concentration decreases anabolic response, cognitive performance, and mood states. The chronic effects of increased cortisol concentration are many: largely related to atherosclerosis development and subsequent cardiovascular disease. Additional issues include anthropometric, endocrine, metabolic, and haemodynamic disturbances. This study makes a strong argument for the rate of thermal acquisition factor. CON and PPE differences in PSI at all measurement points provides justification and support for the changes in other variables. Rapid and uncompensable Tc acquisition needs to be taken into account, as it potentially puts the lives of employees who wear PPE and those around them at risk. / Graduate

Poor oxygenation of solid tumours has been linked with resistance to chemo- and radio-therapy and poor patient outcomes. Measuring the functional status of the tumour vasculature, including blood flow fluctuations and changes in oxygenation is important in cancer staging and therapy monitoring. A robust method is needed for clinical non-invasive measurement of the oxygen supply and demand in tumours. Current clinically approved imaging modalities suffer high cost, long procedure times and limited spatio-temporal resolution. Optoacoustic tomography (OT) is an emerging clinical imaging modality that can provide static images of endogenous haemoglobin concentration and oxygenation. In this work, an integrated framework for quantitative analysis of functional imaging using OT is developed and applied in vivo with preclinical cancer models. Oxygen Enhanced (OE)-OT is established here to provide insight into tumour vascular function and oxygen availability in the tissue. Tracking oxygenation dynamics using OE-OT reveals significant differences between two prostate cancer models in nude mice with markedly different vascular function (PC3 & LNCaP), which appear identical in static OT. OE-OT metrics are shown to be highly repeatable and correlate directly on a per-tumour basis to tumour vascular maturity, hypoxia and necrosis, assessed ex vivo. Dynamic Contrast Enhanced (DCE) OT demonstrates the relationship between OE-OT response and tumour perfusion in vivo. Finally, the possibility of using OT data acquired at longer wavelengths to report on tumour water and lipid content is investigated, with a view to future providing intrinsically co-registered imaging of tumour oxygenation and cellular necrosis. These findings indicate that OE-OT holds potential for application in prostate cancer patients, to improve delineation of aggressive and indolent disease, while combined with DCE-OT, it may offer significant advantage for localised imaging of tumour response to vascular targeted therapies. Further work is needed to establish whether OT can provide a new method to detect tumour necrosis in vivo.

PURPOSE. To image the fundus non-invasively at two different penetration depths using a multispectral imaging system. Monochromatic images at visible spectrum wavelengths and near-infrared wavelengths were qualitatively assessed for choroidal visibility. These images were used calculate oxygen saturation in retinal tissue, optic nerve head tissue, vein, and choroidal tissue in healthy controls and glaucoma patients. METHODS. A fundus camera-based multispectral snapshot oximeter imaged the fundus of healthy subjects and patients with varying ophthalmological pathology. The images of healthy controls and glaucoma patients were analyzed to determine oxygen saturation in the optic nerve head cup and rim, superficial and deep vein, macula and choroidal tissue. RESULTS. Visible: Average oxygen saturation for the ONH cup was 65 ± 6 percent for healthy controls and 61 ± 10 percent for glaucoma patients. For the ONH rim, it was 67 ± 3 percent for healthy controls and 64 ± 17 percent for glaucoma patients. For the vein, it was 67 ± 15 percent for healthy controls and 56 ± 22 percent for glaucoma patients. For the macula, it was 87 ± 10 percent for healthy controls and 93 ± 1 percent for glaucoma patients. NIR: The average oxygen saturation for the vein was 66 ± 20 percent for healthy controls, 58 ± 0.4 percent for glaucoma suspects and 54 ± 17 percent for glaucoma patients. For the choroidal tissue below the macula, it was 99 ± 5 percent in healthy controls and 81 ± 8 percent in glaucoma patients. CONCLUSIONS. Choroidal visibility is enhanced in near infrared monochromatic images from visible spectrum monochromatic images. Oxygen saturation results were lower in glaucoma patients for all anatomical areas analyzed except the avascular macula. / acase@tulane.edu

Lintégrité de la structure et de la dynamique de la membrane plasmatique est essentielle à la fonction de la cellule. Cette intégrité peut être évaluée par la mesure de la fluidité membranaire globale, reflet de lensemble des mouvements des éléments membranaires au sein de la bicouche phospholipidique. Or lintégrité de la membrane est menacée, entre autre, par les modifications de la structure lipidique résultant de lipoperoxidations. Ces peroxidations lipidiques résultent des attaques radicalaires par des espèces oxygénées activées (EOA) produites lors dagression oxydante sur les acides gras membranaires. Nous posons lhypothèse que les conditions doxygénations extrêmes, qui peuvent être rencontrées lors dune anesthésie ou lors dun stress oxydant induit par lexercice chez le cheval, peuvent affecter la fluidité membranaire des érythrocytes et que ces variations peuvent être modulées par la modification de la structure membranaire du globule rouge par un supplément antioxydant oral adéquat. Lobjectif de ce travail est donc dévaluer les effets de différentes conditions doxygénation et doxydation in vitro (par contact avec différents mélanges gazeux), puis in vivo sous anesthésie générale (en faisant varier la fraction inspirée en oxygène) et à lexercice, et enfin dévaluer les effets dune supplémentation enrichie en acides gras de type oméga-3 sur la fluidité membranaire du globule rouge. Les faibles pressions partielles en oxygène dans le sang artériel (PaO2), obtenues in vitro par contact du sang avec un gaz anoxique et in vivo sous anesthésie par inspiration dair ambiant (<45mmHg et <60mmHg respectivement), nont pas eu deffet sur la fluidité ni sur la structure de la membrane érythrocytaire. On peut supposer que le stimulus est insuffisant ou que la protection de la membrane résulte dune capacité antioxydante du plasma et de défenses cellulaires suffisantes. Les pressions partielles élevées en oxygène dans le sang, obtenues in vitro par contact du sang avec de loxygène pur (PaO2>500mmHg), ont induit un stress oxydant modéré qui na pas affecté la structure phospholipidique de la membrane malgré la peroxidation des acides gras de type oméga-6. La fluidité membranaire na pas été affectée par ces facteurs. In vivo, les pressions partielles élevées en oxygène observées dans le sang (>200mmHg) ont été insuffisantes pour induire des peroxidations significatives et des modifications de la fluidité membranaire. En revanche, les valeurs élevées de PaO2 ont augmenté la sensibilité du sang à lhémolyse dans un premier temps, puis sa résistance 24 heures après un retour à la normoxie. Dans ces conditions aucun effet na été noté sur la viscosité du sang ni la perfusion musculaire. Par ailleurs, lexercice intense semble diminuer la fluidité membranaire du globule rouge chez le cheval de sport. Cette diminution sobserve dès 15 minutes après larrêt de lexercice et persiste 24 heures après. Il existe également des corrélations entre certains de ces marqueurs indirects et la fluidité membranaire. La supplémentation na pas eu deffet significatif direct sur lévolution de la fluidité membranaire observée au repos. Mais elle a pourtant influencé la structure de la membrane. En effet, la complémentation a induit une augmentation du pourcentage dacides gras de type oméga-3 contenus dans la membrane érythrocytaire ainsi que du ratio oméga-3/oméga-6 pendant la période de repos. Cela résulte de lincorporation sélective dans la membrane de lacide eicosapentaénoïque (EPA) et de lacide docosahéxaénoïque (DHA) apportés par voie orale. Mais aucune corrélation na été observée dans notre étude entre la composition en acides gras de la membrane et le marqueur de la fluidité membranaire. La supplémentation na pas eu deffet significatif direct sur lévolution de la fluidité membranaire observée à lexercice, mais en a limité la diminution immédiate. Il résulte des études menées que : les conditions doxygénation les plus extrêmes qui peuvent être rencontrées en conditions atmosphériques ne semblent pas affecter la fluidité de la membrane. En revanche, un exercice intense, associé à une demande énergétique accrue, peut induire une diminution de la fluidité membranaire en corrélation avec les marqueurs du stress oxydant. Des modifications de la structure membranaire en acides gras polyinsaturés à longue chaîne de type oméga-3 naffectent pas la fluidité membranaire mais modulent les effets du stress oxydant lors de lexercice. La fluidité membranaire des érythrocytes pourrait être considérée comme un marqueur direct du stress oxydant dans certaines conditions. Mais ce marqueur semble moins sensible et global que dautres marqueurs du stress cellulaire tels que le test dhémolyse ou la mesure de la concentration plasmatique de peroxydes lipidiques spécifiques. The maintenance of plasmatic membrane integrity is mandatory for cell function. This integrity can be assessed by the measurement of global membrane fluidity which is proportional to the whole rotational and lateral diffusion rates of membrane components within the phospholipid bilayer. Membrane integrity could be threatened by changes in lipid structure as a result of lipid peroxidation by free radical species during oxidative stress. We hypothesize that extreme oxygenation status present during anesthesia or during exercise-induced oxidative stress in the horse can alter erythrocyte membrane fluidity (EMF), and that these changes in fluidity depend on variations in erythrocyte membrane structure under the action of an appropriate oral anti-oxidant supplementation. The aims of the study was: to assess the effect(s) of various oxygenation and oxidative conditions firstly created in vitro (by contact between erythrocyte and different gaz mixtures), and secondly in vivo during general anesthesia (with varying inspired oxygen fractions) as well as during exercise. To assess the effects of an omega-3 fatty acid-enriched supplementation on EMF. Low partial oxygen pressures, both obtained in vitro and in vivo under anesthesia (respectively <45 and <60 mmHg) did not have any effect on EMF or membrane structure. Erythrocyte membrane may have been protected by an increase in plasmatic anti-oxidative capacity and cellular defenses. High partial oxygen pressures (>500 mm Hg) obtained in vitro induced a moderate oxidative stress which did not alter the phospholipidic structure of the membrane despite peroxidation of omega 6 fatty acids. Partial oxygen pressures obtained in vivo (>200 mm Hg) were unable to induce significant peroxidation and alteration in membrane fluidity. However, high PaO2 values initially increased sensitivity of blood to hemolysis, followed by a tendency towards resistance to hemolysis after 24hours. Intense exercise decreases EMF in the sports horse. This was observed as soon as 15 minutes after exercise and persisted during the recovery period 24 hours later. Correlations were found between oxidative stress indirect markers and membrane fluidity. Supplementation did not affect membrane fluidity but influenced membrane structure by increasing the pourcentage of omega-3 fatty acids and the omega3/omega6 ratio at rest. These changes resulted from selective incorporation into the membrane of orally provided EPA and DHA . However, we could not evidence a correlation between membrane composition and the marker of membrane fluidity (correlation-relaxation time Tc). During exercise, supplementation had no direct effect on variations of membrane fluidity but tapered its immediate decrease. In conclusion, our studies show that the most extreme conditions encountered under atmospheric conditions do not appear to affect EMF. However intense exercise combined with increased energetic requirements induces a decrease in EMF which correlates with variations in markers of oxidative stress. Modifications of membrane composition in long-chain omega-3 polyinsaturated fatty acids do not affect EMF but modulate oxidative stress during exercise. EMF could be a direct marker of oxidative stress under certain conditions but appears less sensitive and comprehensive than other markers of celllular stress such as the hemolysis test or the concentration in specific lipidic peroxidation products.