Consequences of sarcolemma fatigue on maximal muscle strength production in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

BACKGROUND: Myalgic encephalomyelitis is an invalidating chronic disease often associated with exercise-induced alterations of muscle membrane excitability (M wave). No simultaneous measurements of maximal isometric force production and sarcolemma fatigue in the same muscle group have been previously reported. We hypothesized that M wave alterations could be partly responsible for the reduced muscle force present in this invalidating disease. METHODS: This retrospective study compared two groups of patients who presented (n = 30) or not (n = 28) alterations of M waves evoked by direct muscle stimulation during and after a cycling exercise bout. The maximal handgrip strength was measured before and after exercise, concomitantly with electromyogram recordings from flexor digitorum longus muscle. The patients also answered a questionnaire to identify eventual exacerbation of their clinical symptoms following the exercise test. FINDINGS: The M wave amplitude significantly decreased in muscles and the M wave duration significantly increased in the group of patients with M wave alterations after exercise. Resting values of handgrip were significantly lower in patients with exercise-induced M-wave alterations than in patients without M-wave abnormalities. In patients with exercise-induced M-wave alterations, handgrip significantly decreased after exercise and the changes in handgrip and M wave were positively correlated. The frequency of post-exertion malaise, increased fatigue, myalgia, headache and cognitive dysfunction was significantly higher in patients with M-wave alterations and variations in handgrip after exercise. INTERPRETATION: These data suggest that post-exercise sarcolemma fatigue often measured in patients with myalgic encephalomyelitis could be the cause of muscle failure.

Long-term neuromuscular consequences of SARS-Cov-2 and their similarities with myalgic encephalomyelitis/chronic fatigue syndrome: results of the retrospective CoLGEM study.

BACKGROUND: Patients with long-COVID often complain of continuous fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise. No data are available on EMG recording of evoked myopotentials (M-waves) or exercise-induced alterations in long-COVID patients, providing evidence of muscle membrane fatigue. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develops in more than half of patients after an infectious disease, particularly viral diseases. A large proportion (around 70%) of these patients have neuromuscular disorders with M-wave alterations during and after exercise. Our hypothesis was that M-wave alterations would be also found in long-COVID patients, in association with neuromuscular symptoms, similar to ME/CFS. METHODS: This retrospective observational ColGEM (Covid LonG Encéphalomyelite Myalgique) study compared 59 patients with long-COVID and 55 ME/CFS patients with a history of severe infection who presented before the COVID pandemic. All of these patients underwent the same protocol consisting of a questionnaire focusing on neural and neuromuscular disorders and M-wave recording in the rectus femoris muscle before, during, and 10 min after a progressive cycling exercise. Maximal handgrip strength (MHGS) and maximal exercise power were also measured. The frequency of symptoms and magnitude of M-wave changes in the two groups were compared using non-parametric and parametric tests. RESULTS: The frequency of fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise as well as the magnitude of exercise-induced M-wave alterations were the same in the two groups. By contrast, digestive problems were less present in long-COVID. M-wave alterations were greater in ME/CFS patients as in those with long-COVID when the highest muscle strength and highest exercise performance were measured. CONCLUSIONS: These high clinical and biological similarities between long-COVID and ME/CFS support the hypothesis that SARS-Cov-2 infection can cause ME/CFS symptoms. Trial registration Registered retrospectively.

Altered muscle membrane potential and redox status differentiates two subgroups of patients with chronic fatigue syndrome.

BACKGROUND: In myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), altered membrane excitability often occurs in exercising muscles demonstrating muscle dysfunction regardless of any psychiatric disorder. Increased oxidative stress is also present in many ME/CFS patients and could affect the membrane excitability of resting muscles. METHODS: Seventy-two patients were examined at rest, during an incremental cycling exercise and during a 10-min post-exercise recovery period. All patients had at least four criteria leading to a diagnosis of ME/CFS. To explore muscle membrane excitability, M-waves were recorded during exercise (rectus femoris (RF) muscle) and at rest (flexor digitorum longus (FDL) muscle). Two plasma markers of oxidative stress (thiobarbituric acid reactive substance (TBARS) and oxidation-reduction potential (ORP)) were measured. Plasma potassium (K+) concentration was also measured at rest and at the end of exercise to explore K+ outflow. RESULTS: Thirty-nine patients had marked M-wave alterations in both the RF and FDL muscles during and after exercise while the resting values of plasma TBARS and ORP were increased and exercise-induced K+ outflow was decreased. In contrast, 33 other patients with a diagnosis of ME/CFS had no M-wave alterations and had lower baseline levels of TBARS and ORP. M-wave changes were inversely proportional to TBARS and ORP levels. CONCLUSIONS: Resting muscles of ME/CFS patients have altered muscle membrane excitability. However, our data reveal heterogeneity in some major biomarkers in ME/CFS patients. Measurement of ORP may help to improve the diagnosis of ME/CFS. Trial registration Ethics Committee "Ouest II" of Angers (May 17, 2019) RCB ID: number 2019-A00611-56.

Effect of 4 Weeks of Foot Orthosis Intervention on Ambulatory Capacities and Posture in Normal-Weight and Obese Patients.

BACKGROUND: Several works have shown the benefits of foot orthosis intervention on postural stability in healthy individuals and patients with foot malalignment. However, the effects of foot orthoses on the daily ambulatory activities explored by the Six-Minute Walk Test (6MWT) were never examined. We hypothesized that foot orthoses could increase the gait distance and attenuate the post-6MWT posture alterations already reported in healthy individuals. METHODS: In ten normal-weight (NW) and ten obese patients with foot malalignment and/or abnormal foot arch, we examined the benefits of 4 weeks of custom-molded orthosis intervention (D30) on 6MWT gait distance, fatigue sensation scores, ankle plantarflexion force, and post-6MWT sway of the center of pressure (COP) measured by a pedobarographic platform. Data were compared with those measured in two control-matched groups of ten NW and ten obese individuals, explored at study inclusion and at D30. RESULTS: At study inclusion, the post-6MWT changes in COP surface and the medial and lateral COP deviations were significantly higher in obese participants who needed to wear the foot orthoses compared with obese control subjects. The foot orthosis intervention significantly improved the ambulatory performances of NW and obese individuals during the 6MWT, attenuated the bodily fatigue sensation after the 6MWT, and reduced the post-6MWT COP deviations, with the benefits of insoles being significantly accentuated in obese participants. CONCLUSIONS: Four weeks of foot orthosis intervention significantly increases gait distance and is an effective means to reduce postural sway after walking.

Maximal handgrip strength can predict maximal physical performance in patients with chronic fatigue.

BACKGROUND: Maximal handgrip strength is used to predict exercise performance in healthy older subjects and in patients with chronic obstructive pulmonary disease, breast cancer or cirrhosis. Our objective was to evaluate the ability of maximal handgrip strength to predict maximal exercise performance in patients with chronic fatigue. METHODS: Sixty-six patients with myalgic encephalomyelitis/chronic fatigue syndrome and 32 patients with chronic fatigue but no diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome were included. The maximal physical performance was measured on a cycle ergometer to measure the peak oxygen uptake and the maximal work rate. We searched for linear regressions between maximal handgrip strength and maximal performances. FINDINGS: No significant differences in slopes and ordinates of regression lines were noted between patients with or without a diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, allowing to pool the data. Maximal handgrip strength was significantly and positively correlated with peak oxygen uptake and maximal work rate in all patients with chronic fatigue. INTERPRETATION: We conclude that handgrip strength can predict maximal exercise performance in patients with chronic fatigue.

Understanding neuromuscular disorders in chronic fatigue syndrome.

Muscle failure has been demonstrated in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Neurophysiological tools demonstrate the existence of both central and peripheral fatigue in these patients. Central fatigue is deduced from the reduced amplitude of myopotentials evoked by transcranial magnetic stimulation of the motor cortex as well as by the muscle response to interpolated twitches during sustained fatiguing efforts. An impaired muscle membrane conduction velocity assessed by the reduced amplitude and lengthened duration of myopotentials evoked by direct muscle stimulation is the defining feature of peripheral fatigue. Some patients with ME/CFS show an increased oxidative stress response to exercise. The formation of lipid hydroperoxides in the sarcolemma, which alters ionic fluxes, could explain the reduction of muscle membrane excitability and potassium outflow often measured in these patients. In patients with ME/CFS, the formation of heat shock proteins (HSPs) is also reduced. Because HSPs protect muscle cells against the deleterious effects of reactive oxygen species, the lack of their production could explain the augmented oxidative stress and the consecutive alterations of myopotentials which could open a way for future treatment of ME/CFS.

Adding body load modifies the vibratory sensation of the foot sole and affects the postural control.

BACKGROUND: Heavy backpacks are often used by soldiers and firefighters. Weight carrying could reduce the speed and efficiency in task completion by altering the foot sole sensitivity and postural control. METHODS: In fifteen healthy subjects, we measured the changes in sensitivity to vibrations applied to the foot sole when standing upright or walking after load carrying (30% body weight). The participants were asked to judge different vibration amplitudes applied on the 2nd or 5th metatarsal head and the heel at two frequencies (25 and 150 Hz) to determine the vibration threshold and the global perceptual representation (Ñ°)of the vibration amplitude (Ф) given by the Stevens power function (Ñ° = k × Ð¤n). Any increase in negative k value indicated a reduction in sensitivity to the lowest loads. Pedobarographic measurements, with computation of the center of pressure (COP) and its deviations, were performed during weight carrying. RESULTS: The 25-Hz vibration threshold significantly increased after weight carrying when standing upright or walking. After standing with the added loads, the absolute negative k value increased for the 25 Hz frequency. After walking with the added loads, the k coefficient increased for the two vibration frequencies. Weight carrying significantly increased both the CoP surface and CoP lateral deviation. CONCLUSIONS: Our data show that weight carrying reduces the sensory pathways from the foot sole and accentuates the center of pressure deviations.

Towards Addressing the Body Electrolyte Environment via Sweat Analysis:Pilocarpine Iontophoresis Supports Assessment of Plasma Potassium Concentration.

Electrolyte concentration in sweat depends on environmental context and physical condition but also on the pathophysiological status. Sweat analyzers may be therefore the future way for biological survey although how sweat electrolyte composition can reflect plasma composition remains unclear. We recruited 10 healthy subjects and 6 patients to have a broad range of plasma electrolyte concentrations (chloride, potassium and sodium) and pH. These variables were compared to those found in sweat produced following cycling exercise or pilocarpine iontophoresis, a condition compatible with operating a wearable device. We found no correlation between plasma and sweat parameters when exercise-induced sweat was analyzed, and we could identify a correlation only between plasma and sweat potassium concentration (R = 0.78, p < 0.01) when sweat was induced using pilocarpine iontophoresis. We tested measurement repeatability in sweat at 24hr-interval for 3 days in 4 subjects and found a great intra-individual variability regarding all parameters in exercise-induced sweat whereas similar electrolyte levels were measured in pilocarpine-induced sweat. Thus, electrolyte concentration in sweat sampled following physical activity does not reflect concentration in plasma while pilocarpine iontophoresis appears to be promising to reproducibly address sweat electrolytes, and to make an indirect evaluation of plasma potassium concentration in chronic kidney disease and arrhythmia.

Emergency braking is affected by the use of cruise control.

OBJECTIVE: We compared the differences in the braking response to vehicle collision between an active human emergency braking (control condition) and cruise control (CC) or adaptive cruise control (ACC). METHODS: In 11 male subjects, age 22 to 67 years, we measured the active emergency braking response during manual driving using the accelerator pedal (control condition) or in condition mimicking CC or ACC. In both conditions, we measured the brake reaction time (BRT), delay to produce the peak braking force (PBD), total emergency braking response (BRT + PBD), and peak braking force (PBF). Electromyograms of leg and thigh muscles were recorded during braking. The tonic vibratory response (TVR), Hoffman reflex (HR), and M-waves were recorded in leg muscles to explore the change in sensorimotor control. RESULTS: No difference in PBF, TVR amplitude, HR latency, and Hmax/Mmax ratio were found between the control and CC/ACC conditions. On the other hand, BRT and PBD were significantly lengthened in the CC/ACC condition (240 ± 13 ms and 704 ± 70 ms, respectively) compared to control (183 ± 7 ms and 568 ± 36 ms, respectively). BRT increased with the age of participants and the driving experience shortened PBD and increased PBF. CONCLUSIONS: In male subjects, driving in a CC/ACC condition significantly delays the active emergency braking response to vehicle collision. This could result from higher amplitude of leg motion in the CC/ACC condition and/or by the age-related changes in motor control. Car and truck drivers must take account of the significant increase in the braking distance in a CC/ACC condition.

Consequences of simulated car driving at constant high speed on the sensorimotor control of leg muscles and the braking response.

Due to the increase in time spent seated in cars, there is a risk of fatigue of the leg muscles which adjust the force exerted on the accelerator pedal. Any change in their sensorimotor control could lengthen the response to emergency braking. Fourteen healthy male subjects (mean age: 42 ± 4 years) were explored. Before and after a 1-h driving trial at 120 km h-1 , we measured the braking response, the maximal leg extension and foot inversion forces, the tonic vibratory response (TVR) in gastrocnemius medialis (GM) and tibialis anterior (TA) muscles to explore the myotatic reflex, and the Hoffmann reflex (H-reflex). During driving, surface electromyograms (EMGs) of GM and TA were recorded and the ratio between high (H) and low (L) EMG energies allowed to evaluate the recruitment of high- and low-frequency motor unit discharges. During driving, the H/L ratio decreased in TA, whereas modest and often no significant H/L changes occurred in GM muscle. After driving, the maximal foot inversion force decreased (-19%), while the leg extension force did not vary. Reduced TVR amplitude (-29%) was measured in TA, but no H-reflex changes were noted. The braking reaction time was not modified after the driving trial. Driving at constant elevated speed reduced the myotatic reflex and the recruitment of motor units in TA muscle. The corresponding changes were rarely present in the GM muscle that plays a key role in the braking response, and this could explain the absence of a reduced braking reaction time.

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.

Normal Values of Pressures and Foot Areas Measured in the Static Condition.

BACKGROUND: Podiatric physicians are increasingly using pedobarographs to measure plantar pressure. However, normal values of static pedobarographic variables for healthy men and women are lacking, which makes it difficult to evaluate abnormal foot positioning in standing patients with low- or high-arched feet or painful feet. METHODS: During upright standing, a computerized pedobarograph measured the maximal (Pmax) and mean (Pmean) plantar pressures, total foot area, and forefoot and rearfoot areas in 84 healthy women and 84 healthy men, aged 18 to 83 years. After calibration of the pedobarograph, a correction factor was applied to area measurements, and data repeatability was assessed. RESULTS: The Pmax and Pmean values were not correlated with age but with weight, body mass index, and shoe size. Total foot area was significantly higher in male participants and correlated with body weight, body mass index, and shoe size but not with age. In both sexes, forefoot area was significantly lower than rearfoot area. Significant positive correlations were observed between forefoot and rearfoot areas and weight and shoe size. The forefoot-rearfoot area ratio did not vary with sex, weight, shoe size, and age. CONCLUSIONS: These data provide relationships between Pmax, Pmean, and foot areas and weight and shoe size and clearly indicate no age dependence of pedobarographic data. They also provide stable values of the forefoot-rearfoot area ratio. These data should help clinicians evaluate abnormal foot placement in standing patients.

Spare Adenosine A2a Receptors Are Associated With Positive Exercise Stress Test In Coronary Artery Disease.

During exercise, cardiac oxygen-consumption increases and the resulting low oxygen level in myocardium triggers coronary vasodilation. This response to hypoxia is controlled notably by the vasodilator adenosine and its A2A receptor (A2AR). According to the "spare receptor" pharmacological model, a strong A2AR-mediated response can occur in the context of a large number of receptors remaining unoccupied, activation of only a weak fraction of A2AR (evaluated using KD) resulting in maximal cAMP production (evaluated using EC50), and hence in maximal coronary vasodilation. In coronary artery disease (CAD), myocardial ischemia limits adaptation to exercise, which is commonly detected using the exercise stress test (EST). We hypothesized that spare A2AR are present in CAD patients to correct ischemia. Seventeen patients with angiographically-documented CAD and 17 control subjects were studied. We addressed adenosine-plasma concentration and A2AR-expression at the mononuclear cell-surface, which reflects cardiovascular expression. The presence of spare A2AR was tested using an innovative pharmacological approach based on a homemade monoclonal antibody with agonist properties. EST was positive in 82% of patients, and in none of the controls. Adenosine plasma-concentration increased by 60% at peak exercise in patients only (p<0.01). Most patients (65%), and none of the controls, had spare A2AR (identified when EC50/KD≤0.1) and a low A2AR-expression (mean: -37% vs controls; p<0.01). All patients with spare A2AR had a positive EST whereas the subjects without spare A2AR had a negative EST (p<0.05). Spare A2AR are therefore associated with positive EST in CAD patients and their detection may be used as a diagnostic marker.

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.

Effect of the 6-minute walk test on plantar loading and capability to produce ankle plantar flexion forces.

The six-minute walk test (6MWT) is used to evaluate the ambulatory capacity of patients suffering from respiratory disorders, obesity or neuromuscular diseases. Our primary aim was to evaluate the effects of the 6MWT on the postural sway and the ankle plantar flexion forces in healthy subjects. We measured the ankle plantar flexion forces and the plantar contact area before and after a 6MWT in normal weight and overweight subjects with no history of respiratory, cardiac, and neuromuscular disorders. A post-6MWT sensation of bodily fatigue was evaluated by Multidimensional Fatigue Inventory (MFI) and Pichot fatigue scales. A computerized pedobarographic platform was used to collect the mean plantar contact area, the changes of the center of pressure (CoP) surface and its medial and lateral deviations. In a limited number of subjects, the reproducibility of all the measurements was explored. In both groups, the 6MWT elicited a sensation of bodily fatigue. It also significantly reduced the ankle plantar flexion forces, and increased both the mean plantar contact area and the CoP surface, the changes being not apparent after 10min. The post-6MWT lateral CoP deviations were accentuated in normal weight subjects, while an increase in medial CoP deviations occurred in overweight ones. The 6MWT-induced changes in the plantar flexion force and pedobarographic variables were reproducible. Because this study clearly showed some post-6MWT alterations of the subjects' posture sway of our subjects, we questioned the possible mechanisms occurring that could explain the altered muscle force and the transient destabilization of posture after the 6MWT.

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.

Psychophysical estimate of plantar vibration sensitivity brings additional information to the detection threshold in young and elderly subjects.

OBJECTIVE: Vibration detection threshold of the foot sole was compared to the psychophysical estimate of vibration in a wide range of amplitudes in young (20-34 years old) and elderly subjects (53-67 years old). METHODS: The vibration detection threshold was determined on the hallux, 5th metatarsal head, and heel at frequencies of 25, 50 and 150 Hz. For vibrations of higher amplitude (reaching 360 µm), the Stevens power function (Ψ = k * Φn ) allowed to obtain regression equations between the vibration estimate (Ψ) and its physical magnitude (Φ), the n coefficient giving the subjective intensity in vibration perception. We searched for age-related changes in the vibration perception by the foot sole. RESULTS: In all participants, higher n values were measured at vibration frequencies of 150 Hz and, compared to the young adults the elderly had lower n values measured at this frequency. Only in the young participants, the vibration detection threshold was lowered at 150 Hz. CONCLUSION: The psychophysical estimate brings further information than the vibration detection threshold which is less affected by age. SIGNIFICANCE: The clinical interest of psychophysical vibration estimate was assessed in a patient with a unilateral alteration of foot sensitivity.

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.

Effect of hyperoxic and hyperbaric conditions on the adenosinergic pathway and CD26 expression in rat.

The nucleoside adenosine acts on the nervous and cardiovascular systems via the A2A receptor (A2AR). In response to oxygen level in tissues, adenosine plasma concentration is regulated in particular via its synthesis by CD73 and via its degradation by adenosine deaminase (ADA). The cell-surface endopeptidase CD26 controls the concentration of vasoactive and antioxidant peptides and hence regulates the oxygen supply to tissues and oxidative stress response. Although overexpression of adenosine, CD73, ADA, A2AR, and CD26 in response to hypoxia is well documented, the effects of hyperoxic and hyperbaric conditions on these elements deserve further consideration. Rats and a murine Chem-3 cell line that expresses A2AR were exposed to 0.21 bar O2, 0.79 bar N2 (terrestrial conditions; normoxia); 1 bar O2 (hyperoxia); 2 bar O2 (hyperbaric hyperoxia); 0.21 bar O2, 1.79 bar N2 (hyperbaria). Adenosine plasma concentration, CD73, ADA, A2AR expression, and CD26 activity were addressed in vivo, and cAMP production was addressed in cellulo. For in vivo conditions, 1) hyperoxia decreased adenosine plasma level and T cell surface CD26 activity, whereas it increased CD73 expression and ADA level; 2) hyperbaric hyperoxia tended to amplify the trend; and 3) hyperbaria alone lacked significant influence on these parameters. In the brain and in cellulo, 1) hyperoxia decreased A2AR expression; 2) hyperbaric hyperoxia amplified the trend; and 3) hyperbaria alone exhibited the strongest effect. We found a similar pattern regarding both A2AR mRNA synthesis in the brain and cAMP production in Chem-3 cells. Thus a high oxygen level tended to downregulate the adenosinergic pathway and CD26 activity. Hyperbaria alone affected only A2AR expression and cAMP production. We discuss how such mechanisms triggered by hyperoxygenation can limit, through vasoconstriction, the oxygen supply to tissues and the production of reactive oxygen species.

Cardiopulmonary response to exercise in COPD and overweight patients: relationship between unloaded cycling and maximal oxygen uptake profiles.

Cardiopulmonary response to unloaded cycling may be related to higher workloads. This was assessed in male subjects: 18 healthy sedentary subjects (controls), 14 hypoxemic patients with chronic obstructive pulmonary disease (COPD), and 31 overweight individuals (twelve were hypoxemic). They underwent an incremental exercise up to the maximal oxygen uptake (VO2max), preceded by a 2 min unloaded cycling period. Oxygen uptake (VO2), heart rate (HR), minute ventilation (VE), and respiratory frequency (fR) were averaged every 10 s. At the end of unloaded cycling period, HR increase was significantly accentuated in COPD and hypoxemic overweight subjects (resp., +14 ± 2 and +13 ± 1.5 min(-1), compared to +7.5 ± 1.5 min(-1) in normoxemic overweight subjects and +8 ± 1.8 min(-1) in controls). The fR increase was accentuated in all overweight subjects (hypoxemic: +4.5 ± 0.8; normoxemic: +3.9 ± 0.7 min(-1)) compared to controls (+2.5 ± 0.8 min(-1)) and COPDs (+2.0 ± 0.7 min(-1)). The plateau VE increase during unloaded cycling was positively correlated with VE values measured at the ventilatory threshold and VO2max. Measurement of ventilation during unloaded cycling may serve to predict the ventilatory performance of COPD patients and overweight subjects during an exercise rehabilitation program.