Association of biomarkers with health-related quality of life and history of stressors in myalgic encephalomyelitis/chronic fatigue syndrome patients.

BACKGROUND: Myalgic encephalomyelitis chronic fatigue syndrome (ME/CFS) is a common debilitating disorder associated with an intense fatigue, a reduced physical activity, and an impaired quality of life. There are no established biological markerof the syndrome. The etiology is unknown and its pathogenesis appears to be multifactorial. Various stressors, including intense physical activity, severe infection, and emotional stress are reported in the medical history of ME/CFS patients which raises the question whether any physiological and biological abnormalities usually found in these patients could be indicative of the etiology and/or the quality-of-life impairment. METHODS: Thirty-six patients and 11 age-matched healthy controls were recruited. The following variables that appear to address common symptoms of ME/CFS were studied here: (1) muscle fatigue during exercise has been investigated by monitoring the compound muscle action potential (M-wave); (2) the excessive oxidative stress response to exercise was measured via two plasma markers (thiobarbituric acid reactive substances: TBARS; reduced ascorbic-acid: RAA); (3) a potential inflammatory component was addressed via expression of CD26 on peripheral blood mononuclear cells; (4) quality-of-life impairment was assessed using the London Handicap Scale (LHS) and the Medical Outcome Study Short Form-36 (SF-36). The medical history of each patient, including the presence of stressors such as intense sports practice, severe acute infection and/or severe emotional stress was documented. RESULTS: We observed that: (1) there were striking differences between cases and controls with regard to three biological variables: post-exercise M-wave, TBARS variations and CD26-expression at rest; (2) each of these three variables correlated with the other two; (3) abnormalities in the biomarkers associated with health-related quality of life: the LHS score was negatively correlated with the exercise-induced TBARS increase and positively correlated with CD26-expression while the pain component of SF-36 was negatively correlated with CD26-expression; (4) the TBARS increase and the M-wave decrease were the highest, and the CD26-expression level the lowest in patients who had been submitted to infectious stressors. CONCLUSION: In ME/CFS patients, severe alterations of the muscle excitability, the redox status, as well as the CD26-expression level are correlated with a marked impairment of the quality-of-life. They are particularly significant when infectious stressors are reported in the medical history.

Effectiveness of pure argon for renal transplant preservation in a preclinical pig model of heterotopic autotransplantation.

BACKGROUND: In kidney transplantation, the conditions of organ preservation following removal influence function recovery. Current static preservation procedures are generally based on immersion in a cold-storage solution used under atmospheric air (approximately 78 kPa N2, 21 kPa O2, 1 kPa Ar). Research on static cold-preservation solutions has stalled, and modifying the gas composition of the storage medium for improving preservation was considered. Organoprotective strategies successfully used noble gases and we addressed here the effects of argon and xenon on graft preservation in an established preclinical pig model of autotransplantation. METHODS: The preservation solution Celsior saturated with pure argon (Argon-Celsior) or xenon (Xenon-Celsior) at atmospheric pressure was tested versus Celsior saturated with atmospheric air (Air-Celsior). The left kidney was removed, and Air-Celsior (n = 8 pigs), Argon-Celsior (n = 8) or Xenon-Celsior (n = 6) was used at 4 °C to flush and store the transplant for 30 h, a duration that induced ischemic injury in our model when Air-Celsior was used. Heterotopic autotransplantation and contralateral nephrectomy were performed. Animals were followed for 21 days. RESULTS: The use of Argon-Celsior vs. Air-Celsior: (1) improved function recovery as monitored via creatinine clearance, the fraction of excreted sodium and tubulopathy duration; (2) enabled diuresis recovery 2-3 days earlier; (3) improved survival (7/8 vs. 3/8 pigs survived at postoperative day-21); (4) decreased tubular necrosis, interstitial fibrosis, apoptosis and inflammation, and preserved tissue structures as observed after the natural death/euthanasia; (5) stimulated plasma antioxidant defences during the days following transplantation as shown by monitoring the "reduced ascorbic acid/thiobarbituric acid reactive substances" ratio and Hsp27 expression; (6) limited the inflammatory response as shown by expression of TNF-alpha, IL1-beta and IL6 as observed after the natural death/euthanasia. Conversely, Xenon-Celsior was detrimental, no animal surviving by day-8 in a context where functional recovery, renal tissue properties and the antioxidant and inflammation responses were significantly altered. Thus, the positive effects of argon were not attributable to the noble gases as a group. CONCLUSIONS: The saturation of Celsior with argon improved early functional recovery, graft quality and survival. Manipulating the gas composition of a preservation medium constitutes therefore a promising approach to improve preservation.

Endogenous adenosine release is involved in the control of heart rate in rats.

Intravenous (i.v.) injections of adenosine exert marked effects on heart rate (HR) and arterial blood pressure (BP), but the role of an endogenous adenosine release by vagal stimulation has not been evaluated. In anaesthetized rats, we examined HR and BP changes induced by 1 min electrical vagal stimulation in the control condition, and then after i.v. injections of (i) atropine, (ii) propranolol, (iii) caffeine, (iv) 8 cyclopentyl-1,3-dipropylxanthine (DPCPX), or (v) dipyridamole to increase the plasma concentration of adenosine (APC). APC was measured by chromatography in the arterial blood before and at the end of vagal stimulation. The decrease in HR in the controls during vagal stimulation was markedly attenuated, but persisted after i.v. injections of atropine and propranolol. When first administered, DPCPX modestly but significantly reduced the HR response to vagal stimulation, but this disappeared after i.v. caffeine administration. Both the HR and BP responses were significantly accentuated after i.v. injection of dipyridamole. Vagal stimulation induced a significant increase in APC, proportional to the magnitude of HR decrease. Our data suggest that the inhibitory effects of electrical vagal stimulations on HR and BP were partly mediated through the activation of A1 and A2 receptors by an endogenous adenosine release. Our experimental data could help to understand the effects of ischemic preconditioning, which are partially mediated by adenosine.

The mechanisms of the widespread production of phosphorylated HSP25 after fatiguing muscle stimulation.

We previously showed that a widespread heat shock protein (HSP) response to fatigue of a single hindlimb muscle was responsible for a global adaptive response to an acute localized stress. We also demonstrated that the HSP response resulted from the activation of nerve afferents from the stimulated muscle. However, we did not examine the role played by the different muscle afferents or the efferent arm of HSP response. In the present study we measured the changes in phosphorylated HSP25 (pHSP25) levels in resting hindlimb muscles and the diaphragm, kidney and brain in response to a fatiguing stimulation of one tibialis anterior muscle that was repeated in five series of experiments: (1) intact muscle innervation, (2) during the selective procaine block of conduction in group IV muscle afferents, (3) after muscle nerve transection to suppress all the sensory messages, and under pharmacological blockade of the (4) alpha-adrenergic or (5) glutamatergic neurotransmission. The data showed that: (1) the pHSP25 response in hindlimb muscles resulted from the stimulation of both group III and IV muscle afferents while the pHSP25 response in the diaphragm, kidney and brain resulted from the sole activation of the group IV fibres, and (2) the blockade of alpha-adrenergic, but not glutamatergic, neurotransmission suppressed the pHSP25 response in all explored tissues except the brain. The present study highlights the role played by the group III and IV muscle afferents in the fatigue-induced pHSP25 response and shows that the sympathetic nerve supply to the muscles and kidney represents the efferent arm of the pHSP25 activation. However, the pHSP25 changes in the brain cannot be explained by the pathways investigated here.

Genotoxicity of intraperitoneal injection of lipoamphiphile CdSe/ZnS quantum dots in rats.

The main objective of the present in vivo rat study was to determine the genotoxicity of lipoamphiphile-coated CdSe/ZnS Quantum Dots (QDs), in several organs (brain, liver, kidneys, lungs and testicles). The second objective was to establish the correlations between the QDs genotoxic activity and the oxidative stress, the production of a proinflammatory cytokine (TNF-α), a stress-induced chaperone protein, the phosphorylated heat shock protein 70 (pHsp70), and an increase in the caspase-3 apoptosis factor. Four QDs doses were injected into the peritoneal cavity (5, 5×10(-1), 5×10(-2) and 5×10(-3)µg/kg). DNA lesions in the different organs were measured by the comet assay, and chromosome abnormalities were evaluated by the micronucleus assay on blood reticulocytes (MNRET). Twenty-four hours after the QDs injection, genotoxic effects were observed in the brain and liver and, only for the highest QDs concentration, in testicles. No genotoxic effect was seen in the kidney and lung. The MNRET test revealed a dose-response induction of micronuclei. In parallel, we did neither reveal oxidative stress nor significant variations of TNF-α, pHsp70, and caspase-3. In conclusion, the QDs exerted significant genotoxic effects in the brain and liver, even in the absence of any associated oxidative stress and inflammatory processes.

Fatiguing stimulation of one skeletal muscle triggers heat shock protein activation in several rat organs: the role of muscle innervation.

We hypothesised that activation of muscle afferents by fatigue triggers a widespread activation of heat shock proteins (HSPs) in resting muscles and different organs. In anaesthetised rats, HSP25 and HSP70 levels were determined in both tibialis anterior (TA) and extensor digitorum longus (EDL) muscles and in the diaphragm, kidney and brain by ELISA, which mostly identifies phosphorylated HSP, and western blotting. One TA muscle was electrically stimulated and tissues were sampled 10 or 60 min after the stimulation had ended. The nerve supply to the stimulated TA or its counterpart in the contralateral limb was left intact or suppressed. In control rats, no muscle stimulation was performed and tissues were sampled at the same time points (10 or 60 min). After TA stimulation, ELISA showed an increased HSP25 content in the contralateral TA, EDL and diaphragm at 10 min but not at 60 min, and HSP70 increased in all sampled tissues at 60 min. Western blotting did not show any changes in HSP25 and HSP70 at 10 min, while at 60 min HSP25 increased in all sampled tissues except the brain and HSP70 was elevated in all tissues. Denervation of the contralateral non-stimulated limb suppressed HSP changes in TA and after denervation of the stimulated TA the widespread activation of HSPs in other organs was absent. Our data suggest that fatigue-induced activation of skeletal muscle afferents triggers an early increase in phosphorylated HSP25 in muscles and a delayed elevation of non-phosphorylated HSP25 and HSP70 in skeletal and respiratory muscles, kidney and brain.

Is Oxidative Stress an Emerging Player in the Thrombosis of Patients with Anti-Phosphatidylethanolamine Autoantibodies?

The detection of anti-phosphatidylethanolamine autoantibodies (aPEs) has been proposed to improve the diagnosis and management of patients presenting clinical manifestations of antiphospholipid syndrome (APS), such as thrombosis, and who are persistently negative for conventional markers. After selecting the most specific ELISA for their detection, we evidenced the interest of aPEs in the exploration of thrombosis when APS conventional markers were negative through a 1-year retrospective study including 1131 consecutive patients routinely tested for aPEs. To validate this result, we assessed aPEs in a newly selected population of 77 patients with unexplained deep vein thrombosis (DVT). With a total prevalence of 19.5%, we confirmed the interest of aPE detection in patients with unexplained DVT who were devoid of other aPLs markers. Since endosomal compartment, a source of ROS production, has been recently identified as the cellular target of aPEs in vitro, we then investigated an association between aPE positivity and reactive oxygen species (ROS) production by measuring the production of thiobarbituric acid-reactive substances. We showed, for the first time, a significant association between aPE positivity and systemic ROS production in patients which led us to hypothesize a new mechanism of action of aPEs in thrombosis through a signaling related to oxidative stress.

Hyperoxia-induced alterations in cardiovascular function and autonomic control during return to normoxic breathing.

Hyperoxia causes hemodynamic alterations. We hypothesized that cardiovascular and autonomic control changes last beyond the end of hyperoxic period into normoxia. Ten healthy volunteers were randomized to breathe either medical air or 100% oxygen for 45 min in a double-blind study design. Measurements were performed before (baseline) and during gas exposure, and then 10, 30, 60, and 90 min after gas exposure. Hemodynamic changes were studied by Doppler echocardiography. Changes in cardiac and vasomotor autonomic control were evaluated through changes in spectral power of heart rate variability and blood pressure variability. Cardiac baroreflex sensitivity was assessed by the sequence method. Hyperoxia significantly decreased heart rate and increased the high frequency power of heart rate variability, suggesting a chemoreflex increase in vagal activity since the slope of cardiac baroreflex was significantly decreased during hyperoxia. Hyperoxia increased significantly the systemic vascular resistances and decreased the low frequency power of blood pressure variability, suggesting that hyperoxic vasoconstriction was not supported by an increase in vascular sympathetic stimulation. These changes lasted for 10 min after hyperoxia (p < 0.05). After the end of hyperoxic exposure, the shift of the power spectral distribution of heart rate variability toward a pattern of increased cardiac sympathetic activity lasted for 30 min (p < 0.05), reflecting a resuming of baseline autonomic balance. Cardiac output and stroke volume were significantly decreased during hyperoxia and returned to baseline values (10 min) later than heart rate. In conclusion, hyperoxia effects continue during return to normoxic breathing, but cardiac and vascular parameters followed different time courses of recovery.

Substance P receptor blockade decreases stretch-induced lung cytokines and lung injury in rats.

Overdistension of lung tissue during mechanical ventilation causes cytokine release, which may be facilitated by the autonomic nervous system. We used mechanical ventilation to cause lung injury in rats, and studied how cervical section of the vagus nerve, or substance P (SP) antagonism, affected the injury. The effects of 40 or 25 cmH(2)O high airway pressure injurious ventilation (HV(40) and HV(25)) were studied and compared with low airway pressure ventilation (LV) and spontaneous breathing (controls). Lung mechanics, lung weight, gas exchange, lung myeloperoxidase activity, lung concentrations of interleukin (IL)-1 beta and IL-6, and amounts of lung SP were measured. Control rats were intact, others were bivagotomized, and in some animals we administered the neurokinin-1 (NK-1) receptor blocking agent SR140333. We first determined the durations of HV(40) and HV(25) that induced the same levels of lung injury and increased lung contents of IL-1 beta and IL-6. They were 90 min and 120 min, respectively. Both HV(40) and HV(25) increased lung SP, IL-1 beta and IL-6 levels, these effects being markedly reduced by NK-1 receptor blockade. Bivagotomy reduced to a lesser extent the HV(40)- and HV(25)-induced increases in SP but significantly reduced cytokine production. Neither vagotomy nor NK-1 receptor blockade prevented HV(40)-induced lung injury but, in the HV(25) group, they made it possible to maintain lung injury indices close to those measured in the LV group. This study suggests that both neuronal and extra-neuronal SP might be involved in ventilator-induced lung inflammation and injury. NK-1 receptor blockade could be a pharmacological tool to minimize some adverse effects of mechanical ventilation.

The changes in neuromuscular excitability with normobaric hyperoxia in humans.

Based on previous observations in hyperbaric hyperoxia, we hypothesized that normobaric hyperoxia, often used during general anaesthesia and resuscitation, might also induce a neuromuscular excitability. In healthy volunteers, we studied the consequences of a 50 min period of pure oxygen breathing on the neuromuscular conduction time (CT), the amplitude of the compound evoked muscle potential (M-wave), the latency and amplitude of the Hoffman reflex (H reflex) and the electromyographic tonic vibratory response (TVR) of the flexor digitorum superficialis muscle to explore the proprioceptive reflex loop. Hyperoxia-induced oxidative stress was measured by the changes in blood markers of lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and antioxidant response (reduced ascorbic acid, RAA). During hyperoxia, the M-wave amplitude increased, both CT and H reflex latency were shortened, and the H reflex amplitude increased. By contrast, TVR significantly decreased. Concomitantly, an oxidative stress was assessed by increased TBARS and decreased RAA levels. This study shows the existence of dual effects of hyperoxia, which facilitates the muscle membrane excitability, nerve conduction and spinal reflexes, but reduces the gain of the proprioceptive reflex loop. The activation of the group IV muscle afferents by hyperoxia and the resulting oxidative stress might explain the TVR depression.

Reactive oxygen species activate the group IV muscle afferents in resting and exercising muscle in rats.

We tested the hypothesis that the reactive oxygen species (ROS) produced at rest and mostly during muscle contraction may stimulate the group IV muscle afferents. In rats, afferent activity was recorded in the peroneal nerve innervating the tibialis anterior muscle. Group IV afferents were identified from measurements of their conduction velocity and response to lactic acid. Comparing the group IV response to an intramuscular injection of buffered isotonic NaCl solution, we searched for the effects of a ROS donor (H2O2) or a ROS inhibitor (superoxide dismutase, SOD) on the baseline afferent activity in resting muscles. We also explored the consequences of a pre-treatment with SOD on the afferent nerve response to H2O2 injection or electrical muscle stimulation (MS). In other animals, we measured the changes in intramuscular level of a marker of oxidative stress (isoprostanes) after each test agent. H2O2 injection markedly activated all recorded group IV afferents. SOD injection lowered the baseline activity of 50 out of 70 afferent units, suppressed the afferent response to H2O2 injection, and delayed and reduced the MS-induced activation of all recorded units. Intramuscular isoprostanes level significantly increased after H2O2 injection or MS, the oxidative stress being absent in muscles pre-treated with SOD. We concluded that ROS influence both the spontaneous and contraction-induced activities of the group IV muscle afferents and are a potent stimulus of muscle metaboreceptors.

High-frequency percussive ventilation attenuates lung injury in a rabbit model of gastric juice aspiration.

OBJECTIVE: To test the effects of high-frequency percussive ventilation (HFPV) compared with high-frequency oscillatory ventilation (HFOV) and low-volume conventional mechanical ventilation (LVCMV), on lung injury course in a gastric juice aspiration model. DESIGN: Prospective, randomized, controlled, in-vivo animal study. SETTING: University animal research laboratory. SUBJECTS: Forty-three New Zealand rabbits. INTERVENTIONS: Lung injury was induced by intratracheal instillation of human gastric juice in order to achieve profound hypoxaemia (PaO2/FIO2< or =50). Animals were ventilated for 4h after randomization in one of the following four groups: HFPV (median pressure 15cmH2O); LVCMV (VT 6mlkg(-1) and PEEP set to reach 15cmH2O plateau pressure); HFOV (mean pressure 15cmH2O); and a high-volume control group HVCMV (VT 12ml kg(-1) and ZEEP). MEASUREMENTS AND RESULTS: Static respiratory compliance increased after the ventilation period in the HFPV, LVMCV and HFOV groups, in contrast with the HVCMV group. PaO2/FIO2 improved similarly in the HFPV, LVCMV and HFOV groups, and remained lower in the HVCMV group than in the three others. Lung oedema, myeloperoxidase and histological lung injury score were higher in the HVCMV group, but not different among all others. Arterial lactate markedly increased after 4h of ventilation in the HVCMV group, while lower but similar levels were observed in the three other groups. CONCLUSION: HFPV, like HFOV and protective CMV, improves respiratory mechanics and oxygenation, and attenuates lung damage. The HFPV provides attractive lung protection, but further studies should confirm these results before introducing HFPV into the clinical arena.

Physiological, histological and biochemical properties of rat skeletal muscles in response to hindlimb suspension.

In previous study, we found that the reduced exercise-induced production of reactive oxygen species (ROS) reported in slow-oxidative muscle of hypoxemic rats and also in chronic hypoxemic patients did not simply result from deconditioning. In control rats and after a 3-week period of hindlimb suspension (HS), the slow-oxidative (Soleus, SOL) and fast-glycolytic skeletal muscles (Extensor digitorum longus, EDL) were sampled. We determined the response to direct muscle stimulation (twitch stimulation (TS), Maximal force (Fmax)), twitch amplitude and maximal relaxation rate, tetanic frequency, endurance to fatigue after muscle stimulation (MS), the different fibre types based on their myofibrillar adenosinetriphosphatase (ATPase) activity, and the intra-muscular redox status (Thiobarbituric Acid Reactive Sustances: TBARS, reduced glutathione: GSH, reduced ascorbic acid: RAA). After the 3-w HS period: (1) the contractile properties were modified in SOL only (reduced Fmax and twitch amplitude, increased tetanic frequency); (2) the fibre typology was modified in both muscles (in SOL: increased proportion of IIa and IIc fibres, in EDL: increased proportion of IId/x fibres but decreased proportion of IIb fibres); and (3) only in SOL, the TBARS level increased and the GSH and RAA concentrations decreased at rest and after fatiguing MS. Thus, HS accentuates the exercise-induced ROS production in slow-oxidative muscle in a direction opposite to that measured in chronic hypoxemic rats. This strongly suggests that hypoxemia reduces the ROS production independently from any muscle disuse.

Enhanced exercise-induced plasma cytokine response and oxidative stress in COPD patients depend on blood oxygenation.

In healthy subjects, hypoxemia and exercise represent independent stressors promoting the exercise-induced cytokine response and oxidative stress. We hypothesized that hypoxemia in patients with chronic obstructive pulmonary disease (COPD) may affect the cytokine production and/or the changes in oxidant-antioxidant status in response to maximal exercise. Exercise-induced changes in PaO2 allowed to transiently increase or decrease baseline hypoxemia and to point out its specific action on muscle metabolism. COPD patients with severe to moderate hypoxemia (56 < PaO2 < 72 mmHg) performed an incremental cycling exercise until volitional exhaustion. Two cytokines [interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha] and three blood indices of oxidative stress [plasma thiobarbituric acid reactive substances (TBARS) and two antioxidants, reduced erythrocyte glutathione (GSH), and reduced plasma ascorbic acid, RAA] were measured at rest, then during and after exercise. The changes in the cytokine levels and oxidant-antioxidant status were analysed in relation with the baseline PaO2 and its exercise-induced variations. Data were compared with those obtained in an age- and body mass index-matched group of healthy subjects. Compared with healthy subjects, COPD patients presented a marked accentuation of exercise-induced increase in IL-6 level and earlier changes in their oxidant-antioxidant status. Resting levels of IL-6 and TNF-alpha and exercise-induced peak variations of TBARS, IL-6 and TNF-alpha were negatively correlated with the baseline PaO2. In COPD patients, the peak increases in IL-6 and TBARS were attenuated when exercise hyperventilation reduced the baseline hypoxemia. Our study indicates that the PaO2 level affects both the exercise-induced oxidative stress and cytokine response in hypoxemic COPD patients.

Cytokine and oxidative responses to maximal cycling exercise in sedentary subjects.

INTRODUCTION: The simultaneous determination of the time course and magnitude of oxidative stress indicators and cytokine changes elicited by maximal incremental exercise has not yet been published for healthy sedentary subjects. PURPOSE: The determination of normal exercise-induced changes in oxidant-antioxidant status and plasma cytokine represents a fundamental step before exploring patients suspected of altered biochemical responses. METHODS: Fifteen healthy sedentary subjects performed an incremental cycle exercise until volitional exhaustion with measurement of maximal oxygen uptake (VO2max), two cytokines (IL-6 and TNF-alpha), and three indicators of oxidative stress (plasma thiobarbituric acid reactive substances (TBARS), reduced erythrocyte glutathione (GSH), and reduced plasma ascorbic acid (RAA)). RESULTS: At VO2max, we noted a significant increase in plasma IL-6 and TNF-alpha concentrations, concomitant with the decrease in plasma RAA level. Besides, the plasma TBARS increase and erythrocyte GSH decrease respectively occurred at the 5th and 10th minutes of recovery. The exercise-induced variations of all blood indicators were completed within the 20th minute of the recovery period. We found significant positive correlations between VO2max and the peak increases in IL-6 (but not TNF-alpha) and TBARS. The corresponding variations of IL-6 and TBARS were also correlated. CONCLUSION: This study indicates that blood samples for analyses of changes in both oxidant-antioxidant status and cytokine levels in response to maximal cycling exercise must be performed within the first 20 min of the postexercise recovery period.

Reliability of different blood indices to explore the oxidative stress in response to maximal cycling and static exercises.

This study compares the changes in four blood markers of exercise-induced oxidative stress in response to exercise protocols commonly used to explore the global muscle performance at work (maximal incremental cycle) and endurance to fatigue of selected muscles (static handgrip and thumb adduction). Cycling and static exercises allow the muscle to work in aerobic and anaerobic conditions, respectively. Healthy adults performed an incremental cycling exercise until volitional exhaustion and, on separated days, executed infra-maximal static thumb adduction and handgrip until exhaustion. Exercise-induced oxidative stress was assessed by the increased plasma concentration of thiobarbituric acid reactive substances (TBARS), the consumption of plasma reduced ascorbic acid (RAA), and erythrocyte reduced glutathione (GSH) antioxidants, and the changes in the total antioxidant status (TAS) of plasma. Five minutes after the end of the incremental cycling exercise, we measured a peak increase in TBARS level, maximal consumption of GSH and RAA, and a modest but significant decrease in TAS concentration. In response to both static thumb adduction and handgrip, significant variations of TBARS, GSH and RAA occurred but we did not measure any significant change in TAS level throughout the 20-min recovery period of both exercise bouts. The present study shows that only the changes in TBARS, GSH and RAA explore both dynamic and static exercises. In addition, TAS measurement does not seem to represent a reliable and unique tool to explore exercise-induced oxidative stress, at least during isometric efforts that allow the muscle to work under anaerobic condition.

Pathophysiological and diagnostic implications of cardiac biomarkers and antidiuretic hormone release in distinguishing immersion pulmonary edema from decompression sickness.

Immersion pulmonary edema (IPE) is a misdiagnosed environmental illness caused by water immersion, cold, and exertion. IPE occurs typically during SCUBA diving, snorkeling, and swimming. IPE is sometimes associated with myocardial injury and/or loss of consciousness in water, which may be fatal. IPE is thought to involve hemodynamic and cardiovascular disturbances, but its pathophysiology remains largely unclear, which makes IPE prevention difficult. This observational study aimed to document IPE pathogenesis and improve diagnostic reliability, including distinguishing in some conditions IPE from decompression sickness (DCS), another diving-related disorder.Thirty-one patients (19 IPE, 12 DCS) treated at the Hyperbaric Medicine Department (Ste-Anne hospital, Toulon, France; July 2013-June 2014) were recruited into the study. Ten healthy divers were recruited as controls. We tested: (i) copeptin, a surrogate marker for antidiuretic hormone and a stress marker; (ii) ischemia-modified albumin, an ischemia/hypoxia marker; (iii) brain-natriuretic peptide (BNP), a marker of heart failure, and (iv) ultrasensitive-cardiac troponin-I (cTnI), a marker of myocardial ischemia.We found that copeptin and cardiac biomarkers were higher in IPE versus DCS and controls: (i) copeptin: 68% of IPE patients had a high level versus 25% of DCS patients (P < 0.05) (mean ±â€Šstandard-deviation: IPE: 53 ±â€Š61 pmol/L; DCS: 15 ±â€Š17; controls: 6 ±â€Š3; IPE versus DCS or controls: P < 0.05); (ii) ischemia-modified albumin: 68% of IPE patients had a high level versus 16% of DCS patients (P < 0.05) (IPE: 123 ±â€Š25 arbitrary-units; DCS: 84 ±â€Š25; controls: 94 ±â€Š7; IPE versus DCS or controls: P < 0.05); (iii) BNP: 53% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 383 ±â€Š394 ng/L; DCS: 37 ±â€Š28; controls: 19 ±â€Š15; IPE versus DCS or controls: P < 0.01); (iv) cTnI: 63% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 0.66 ±â€Š1.50 µg/L; DCS: 0.0061 ±â€Š0.0040; controls: 0.0090 ±â€Š0.01; IPE versus DCS or controls: P < 0.01). The combined "BNP-cTnI" levels provided most discrimination: all IPE patients, but none of the DCS patients, had elevated levels of either/both of these markers.We propose that antidiuretic hormone acts together with a myocardial ischemic process to promote IPE. Thus, monitoring of antidiuretic hormone and cardiac biomarkers can help to make a quick and reliable diagnosis of IPE.

Acute hypoxemia does not increase the oxidative stress in resting and contracting muscle in humans.

In healthy humans sustaining static handgrip at 60% of maximal voluntary contraction (MVC) until exhaustion, we measured the venous blood concentration of reduced ascorbic acid (RAA) and thiobarbituric acid reactive substances (TBARS), respectively, used as markers of the post-exercise oxidative stress and lipid peroxidation. Measurements were conducted in normoxemia, then during a 30-min period of hypoxemia (PaO2 = 56 mmHg) produced by inhalation of an hypoxic gas mixture. Compared to normoxemia, hypoxemia did not significantly modify the resting concentrations of TBARS and RAA, and did not affect the consumption of ascorbic acid after 60% MVC but suppressed the post-exercise TBARS increase. We conclude that acute hypoxemia does not modify the production of oxygen free radicals after strenuous static efforts and even seems to attenuate the lipid peroxidation.

The oxidative stress in response to routine incremental cycling exercise in healthy sedentary subjects.

The kinetics of blood markers of the oxidative stress during and after an incremental exercise until the maximal performances is not documented in healthy sedentary subjects. We studied subjects of both sexes cycling on an ergometer until or near the V(O)(2)(max) measurement, and we measured during exercise and a 30-min recovery period the plasma concentration of thiobarbituric acid reactive substances (TBARS) which explored the production of reactive oxygen species (ROS) and two antioxidants (plasma reduced ascorbic acid (RAA) and erythrocyte reduced glutathione (GSH)). Despite we noted inter-individual differences in the instants of maximal variations of TBARS, GSH, and RAA, they were all measured within the first 20 min of the post-exercise recovery period, and at the 30th min of recovery, the three ROS blood markers tended to recover their pre-exercise levels. The maximal TBARS increase was positively correlated with V(O)(2)(max) and negatively correlated with the magnitude of RAA consumption. Our results indicate the existence of an early post-exercise oxidative stress in healthy sedentary volunteers. They also show that the ROS production is proportional to the maximal aerobic power and inversely related to the consumption of plasma antioxidants.

Reduced oxidative stress and blood lactic acidosis in trained breath-hold human divers.

We hypothesized that the repetition of brief epochs of hypoxemia in elite human breath-hold divers could induce an adaptation of their metabolic responses, resulting in reduced blood acidosis and oxidative stress. Trained divers who had a 7-10 year experience in breath-hold diving, and were able to sustain apnea up to 440 sec at rest, were compared to control individuals who sustained apnea for 145 sec at the most. The subjects sustained apnea at rest (static apnea), and then, performed two 1-min dynamic forearm exercises whether they breathed (control exercise) or sustained apnea (dynamic apnea). We measured arterial blood gases, venous blood pH, and venous blood concentrations of lactic acid, thiobarbituric acid reactive substances (TBARS), and two endogenous anti-oxidants (reduced glutathione, GSH, and reduced ascorbic acid, RAA). In control subjects, the three experimental conditions elicited an increase in blood lactic acid concentration and an oxidative stress (increased TBARS, decreased GSH and RAA concentrations). In divers, the changes in lactic acid, TBARS, RAA, and GSH concentrations were markedly reduced after static and dynamic apnea, as well as after control exercise. Thus, human subjects involved in a long duration training programme of breath-hold diving have reduced post-apnea as well as post-exercise blood acidosis and oxidative stress, mimicking the responses of diving animals.