Stephane Delliaux

Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise

Objectives.  Because the muscle response to incremental exercise is not well documented in patients suffering from chronic fatigue syndrome (CFS), we combined electrophysiological (compound‐evoked muscle action potential, M wave), and biochemical (lactic acid production, oxidative stress) measurements to assess any muscle dysfunction in response to a routine cycling exercise.

Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses.

Objectives.  As heat shock proteins (Hsp) protect the cells against the deleterious effects of oxidative stress, we hypothesized that Hsp expression might be reduced in patients suffering from chronic fatigue syndrome (CFS) who present an accentuated exercise‐induced oxidative stress.

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.

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.

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.

Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins

Abstract.  Jammes Y, Steinberg JG, Delliaux S (Aix‐Marseille University, Marseille, France). Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins. J Intern Med 2012; 272: 74–84.

Effects of hypoxia on muscle response to tendon vibration in humans.

Previous animal studies have shown that hypoxia markedly reduces the activation of muscle spindles. The present study was undertaken to determine whether a reduced oxygen supply to muscle affects the tonic vibration reflex (TVR) in humans. In resting healthy volunteers, the effects of inhalation of hypoxic gas, apnea, and total forearm ischemia produced by cuff inflation were studied on separate days. The TVR was recorded in flexor digitorum superficialis and the neuromuscular conduction time (CT) was measured from the compound muscle action potential; the latency and amplitude of the H reflex were also determined. TVR depression began during inhalation of the hypoxic gas, at the end of apnea, and during cuff inflation, and persisted during the recovery period. The H‐reflex amplitude concomitantly increased or remained unchanged. Thus, hypoxia seems to directly alter muscle spindle reactivity. Such alterations of sensorimotor control may occur in patients suffering from respiratory or circulatory insufficiency and may contribute to their exercise limitation. Muscle Nerve, 2006

Evaluation of muscle metaboreflex function through graded reduction in forearm blood flow during rhythmic handgrip exercise in humans

Hypoperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex. Our aim was to determine the muscle metaboreflex threshold and gain in humans by creating an open-loop relationship between active muscle blood flow and hemodynamic responses during a rhythmic handgrip exercise. Eleven healthy subjects performed the exercise at 5 or 15% of maximal voluntary contraction (MVC) in random order. During the exercise, forearm blood flow (FBF), which was continuously measured using Doppler ultrasound, was reduced in five steps by manipulating the inner pressure of an occlusion cuff on the upper arm. The FBF at each level was maintained for 3 min. The initial reductions in FBF elicited no hemodynamic changes, but once FBF fell below a threshold, mean arterial blood pressure (MAP) and heart rate (HR) increased and total vascular conductance (TVC) decreased in a linear manner. The threshold FBF during the 15% MVC trial was significantly higher than during the 5% MVC trial. The gain was then estimated as the slope of the relationship between the hemodynamic responses and FBFs below the threshold. The gains for the MAP and TVC responses did not differ between workloads, but the gain for the HR response was greater in the 15% MVC trial. Our findings thus indicate that increasing the workload shifts the threshold for the muscle metaboreflex to higher blood flows without changing the gain of the reflex for the MAP and TVC responses, whereas it enhances the gain for the HR response.

Fatigue-induced changes in tonic vibration response (TVR) in humans: relationships between electromyographic and biochemical events.

Fatigue‐induced changes in the proprioceptive reflex loop were explored in humans by using the tonic electromyographic (EMG) response to vibration (TVR) and relating it to lactic acidosis (LA) and oxidative stress. TVR was measured in flexor digitorum superficialis before and after sustained or intermittent handgrip at maximal voluntary contraction (MVC). TVR variations were compared with the changes in EMG power spectrum preceding contractile fatigue, the Hoffman reflex (H‐reflex), and plasma concentrations of LA and thiobarbituric acid reactive substances (TBARS). After both sustained and intermittent handgrips, TVR amplitude first declined then increased, independently from the changes in EMG power spectrum and H‐reflex. TVR depression and facilitation were respectively concomitant with increases in LA and TBARS. The TVR depression was proportional to the increased LA level. The origin of TVR changes after muscle fatigue is questioned because the relationship between TVR depression and LA accumulation might be temporal, not causal, and changes in muscle stiffness were not explored. Muscle Nerve, 2008.

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)‐α] 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‐α and exercise‐induced peak variations of TBARS, IL‐6 and TNF‐α 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.