Jean Guillaume Steinberg

Effects of acute hypoxemia on force and surface EMG during sustained handgrip

Data on the consequences of acute hypoxemia on the strength of contraction are often contradictory. In healthy subjects, we tested the effects of hypoxemia (PaO2 = 56 mmHg), maintained for a 30‐min period, on static handgrip elicited by voluntary effort or direct electrical muscle stimulation, in order to separate the consequences of hypoxemia on central or peripheral factors, respectively. Force was measured during maximal voluntary contractions (MVCs), 60% MVCs sustained until exhaustion, and 1‐min periods of electrical muscle stimulation at 60 HZ. The evoked compound muscle action potential (M wave) was recorded in resting muscle and after each period of 60‐HZ stimulation or sustained 60% MVC. Power spectrum analysis of surface electromyogram (EMG) was performed during sustained 60% MVC. Compared to normoxemia, acute hypoxemia lowered MVC (−12%, P < 0.01) but enhanced (+38%, P < 0.01) the peak force elicited by electrical muscle stimulation. In resting muscle, hypoxemia had no influence on the M‐wave amplitude but lengthened the neuromuscular transmission time(+740 μs, P < 0.05). Hypoxemia did not alter the M wave measured after 60 HZ stimulation and 60% MVC. During sustained 60% MVC, hypoxemia markedly depressed the EMG changes, abolishing the leftward shift of power spectra. These data show that acute hypoxemia reduces MVC through depression of the central drive, whereas it improves the peripheral muscle response to electrical stimulation. In addition, hypoxemia reduces the recruitment of slow firing motor unit, which are highly oxygen‐dependent. This could constitute an adaptative muscle response to a reduced oxygen supply.

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.

Breath-hold training of humans reduces oxidative stress and blood acidosis after static and dynamic apnea.

Repeated epochs of breath-holding were superimposed to the regular training cycling program of triathletes to reproduce the adaptative responses to hypoxia, already described in elite breath-hold divers [Respir. Physiol. Neurobiol. 133 (2002) 121]. Before and after a 3-month breath-hold training program, we tested the response to static apnea and to a 1-min dynamic forearm exercise executed during apnea (dynamic apnea). The breath-hold training program did not modify the maximal performances measured during an incremental cycling exercise. After training, the duration of static apnea significantly lengthened and the associated bradycardia was accentuated; we also noted a reduction of the post-apnea decrease in venous blood pH and increase in lactic acid concentration, and the suppression of the post-apnea oxidative stress (increased concentration of thiobarbituric acid reactive substances). After dynamic apnea, the blood acidosis was reduced and the oxidative stress no more occurred. These results suggest that the practice of breath-holding improves the tolerance to hypoxemia independently from any genetic factor.

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.

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.

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 (PaO 2 =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 post-exercise oxidative stress is depressed by acetylsalicylic acid.

In order to assess whether oxidative stress occurs after fatiguing dynamic contractions of a small forearm muscle group, we estimated the kinetics of changes in some of its biomarkers (thiobarbituric acid reactive substances or TBARS; plasma reduced ascorbic acid or RAA; erythrocyte reduced glutathione or GSH). We also tested the hypothesis that acetylsalicylic acid (ASA) may compete with endogenous radical targets, attenuating the post-exercise oxidative stress. Seven male subjects successively performed a 3-min dynamic handgrip exercise with the dominant and then the contralateral forearm. Blood samples were taken from an antecubital vein in each exercising forearm. Biochemical analyses, including the concentration measurements of lactic acid, potassium, and oxidative stress markers were performed at rest and then during the 30-min period of recovery following each exercise. The same day, exercises were repeated after ingestion of a single dose (10 mg/kg) of ASA, and the same exercises were performed after a 3-day ASA treatment (30 mg/kg/day). In control condition, the changes in TBARS, RAA and GSH were already significant immediately after the end of the forearm exercise. They culminated after 5 min, and control values were recovered by a 30-min rest period. We verified that repeated bouts failed to alter the post-exercise variations. ASA did not modify the lactic acid production significantly, though the 3-day ASA treatment significantly reduced the efflux of potassium (-74%, P < 0.05), and the post-exercise variations of TBARS (-45%, P < 0.01), RAA (-44%, P < 0.01) and GSH (-48%, P < 0.01). These results suggest that the dynamic handgrip exercise is a good model for studying the post-exercise oxidative stress and also that ASA seems to offer an efficient protection against oxidative stress and the changes in membrane permeability to potassium.

Influence of chronic hypoxemia on peripheral muscle function and oxidative stress in humans.

Transient re‐oxygenation of humans suffering from chronic obstructive pulmonary disease (COPD) allows the assessment of the consequences of chronic hypoxemia on peripheral muscle and metabolism apart from the effects of de‐conditioning. The subjects performed maximal voluntary contractions (MVC) of flexor digitorum and vastus lateralis muscles and sustained infra‐maximal contractions. COPD patients repeated the whole challenge during a 50‐min oxygen breathing period and after recovery to baseline hypoxemia. We measured the compound evoked muscle mass action potential (M‐wave) and the medium frequency (MF) of surface electromyography (EMG) power spectrum. Blood lactate (LA) and potassium (K+), erythrocyte‐reduced glutathione (GSH), and plasma thiobarbituric acid reactive substances (TBARS) were also measured. Compared with a control group, COPD patients had lower MVCs, an attenuated decrease in MF during exercise, lower resting level of GSH, no posthandgrip TBARS increase and no GSH consumption. Reoxygenation (1) increased MVCs, (2) accentuated the MF decline and (3) elicited a posthandgrip TBARS increase and GSH consumption. Thus, we conclude that chronic hypoxemia exerts specific muscular effects: a reduced force production, an attenuated ‘muscle wisdom’, and the suppression of the exercise oxidative stress.

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.