Stéphane Doutreleau

Effect of interval versus continuous training on cardiorespiratory and mitochondrial functions: relationship to aerobic performance improvements in sedentary subjects

The goal of the study was to determine the effects of continuous (CT) vs. intermittent (IT) training yielding identical mechanical work and training duration on skeletal muscle and cardiorespiratory adaptations in sedentary subjects. Eleven subjects (6 men and 5 women, 45 +/- 3 years) were randomly assigned to either of the two 8-wk training programs in a cross-over design, separated by 12 wk of detraining. Maximal oxygen uptake (Vo2max) increased after both trainings (9% with CT vs. 15% with IT), whereas only IT was associated with faster Vo2 kinetics (tau: 68.0 +/- 1.6 vs. 54.9 +/- 0.7 s, P < 0.05) measured during a test to exhaustion (TTE) and with improvements in maximal cardiac output (Qmax, from 18.1 +/- 1.1 to 20.1 +/- 1.2 l/min; P < 0.01). Skeletal muscle mitochondrial oxidative capacities (Vmax) were only increased after IT (3.3 +/- 0.4 before and 4.5 +/- 0.6 micromol O2 x min(-1) x g dw(-1) after training; P < 0.05), whereas capillary density increased after both trainings, with a two-fold higher enhancement after CT (+21 +/- 1% for IT and +40 +/- 3% after CT, P < 0.05). The gain of Vmax was correlated with the gain of TTE and the gain of Vo2max with IT. The gain of Qmax was also correlated with the gain of VO2max. These results suggest that fluctuations of workload and oxygen uptake during training sessions, rather than exercise duration or global energy expenditure, are key factors in improving muscle oxidative capacities. In an integrative view, IT seems optimal in maximizing both peripheral muscle and central cardiorespiratory adaptations, permitting significant functional improvement. These data support the symmorphosis concept in sedentary subjects.

Heart rate variability in sportive elderly: relationship with daily physical activity.

PURPOSE Aging is associated with decreased heart rate variability (HRV). As aerobic training is known to increase HRV, the purpose of this study was to evaluate the influence of long-term lifestyle on HRV in very old adults with regard to their usual physical activity. METHODS Twenty-four older adults (mean 75.7 +/- 0.2 yr) were divided into two groups according to their sport activities assessed by the Modified Baecke Questionnaire for Older Adults. Sedentary subjects (SED) were compared to elderly regularly involved in sport activities (SP). The subjects were supine for 20 min and the last 5 min were used to determine HR and HRV indexes as the standard deviation of normal intervals (SDNN), the root-mean-square differences of successive normal R-R intervals (RMSSD), and the high-frequency (HF) and low-frequency (LF) power. Physical activity was evaluated during 1 wk by triaxial accelerometry and analyzed in terms of intensity and duration. RESULTS Daily physical activity energy expenditure given by the accelerometer was significantly higher in SP than in SED (P < 0.05). SP spent more time per week in activity of intensity higher than 3 resting metabolic equivalents (METs), but total activity time was significantly higher for SED than for SP (P < 0.05). SP showed significantly (P < 0.05) lower resting heart rate than SED, higher global HRV (SDNN), and higher parasympathetic-related HRV indexes (RMSSD, HF, and HF/(LF+HF)) (P < 0.05). CONCLUSIONS Our results indicate that in very old subjects a long-term sportive lifestyle, which increases total daily energy expenditure and physical activity intensity, is associated with higher global HRV and vagal-related indexes and thus may counteract the age-related decline in cardiac autonomic control better than a sedentary lifestyle.

Recognition and Significance of Pathological T-Wave Inversions in Athletes

Background— Pathological T-wave inversion (PTWI) is rarely observed on the ECG of healthy athletes, whereas it is common in patients with certain cardiac diseases. All ECG interpretation guidelines for use within athletes state that PTWI (except in leads aVR, III and V1 and in V1–V4 when preceded by domed ST segment in asymptomatic Afro-Caribbean athletes only) cannot be considered a physiological adaptation. The aims of the present study were to prospectively determine the prevalence of cardiac pathology in athletes presenting with PTWI, and to examine the efficacy of cardiac magnetic resonance in the work-up battery of further examinations. Methods and Results— Athletes presenting with PTWI (n=155) were investigated with clinical examination, ECG, echocardiography, exercise testing, 24h Holter ECG, and cardiac magnetic resonance. Cardiac disease was established in 44.5% of athletes, with hypertrophic cardiomyopathy (81%) the most common pathology. Echocardiography was abnormal in 53.6% of positive cases, and cardiac magnetic resonance identified a further 24 athletes with disease. Five athletes (7.2%) considered normal on initial presentation subsequently expressed pathology during follow-up. Familial history of sudden cardiac death and ST-segment depression associated with PTWI were predictive of cardiac disease. Conclusions— PTWI should be considered pathological in all cases until proven otherwise, because it was associated with cardiac pathology in 45% of athletes. Despite echocardiography identifying pathology in half of these cases, cardiac magnetic resonance must be considered routine in athletes presenting with PTWI with normal echocardiography. Although exclusion from competitive sport is not warranted in the presence of normal secondary examinations, annual follow-up is essential to ascertain possible disease expression.

Dehydroepiandrosterone (DHEA) improves pulmonary hypertension in chronic obstructive pulmonary disease (COPD): a pilot study.

OBJECTIVES It was previously shown that dehydroepiandrosterone (DHEA) reverses chronic hypoxia-induced pulmonary hypertension (PH) in rats, but whether DHEA can improve the clinical and hemodynamic status of patients with PH associated to chronic obstructive pulmonary disease (PH-COPD) has not been studied whereas it is a very severe poorly treated disease. PATIENTS AND METHODS Eight patients with PH-COPD were treated with DHEA (200mg daily orally) for 3 months. The primary end-point was the change in the 6-minute walk test (6-MWT) distance. Secondary end-points included pulmonary hemodynamics, lung function tests and tolerance of treatment. RESULTS The 6-MWT increased in all cases, from 333m (median [IQR]) (257; 378) to 390m (362; 440) (P<0.05). Mean pulmonary artery pressure decreased from 26mmHg (25; 27) to 21.5mmHg (20; 25) (P<0.05) and pulmonary vascular resistance from 4.2UI (3.5; 4.4) to 2.6UI (2.5; 3.8) (P<0.05). The carbon monoxide diffusing capacity of the lung (DLCO % predicted) increased significantly from 27.4% (20.1; 29.3) to 36.4% (14.6; 39.6) (P<0.05). DHEA treatment did not change respiratory parameters of gas exchange and the 200mg per day of DHEA used was perfectly tolerated with no side effect reported. CONCLUSION DHEA treatment significantly improves 6-MWT distance, pulmonary hemodynamics and DLCO of patients with PH-COPD, without worsening gas exchange, as do other pharmacological treatments of PH (trial registration NCT00581087).

Pulmonary hemodynamics during a strenuous intermittent exercise in healthy subjects.

PURPOSE It has been suggested that an intermittent work exercise test (IWET) is as efficient but better tolerated than continuous exercise for rehabilitation. Although systemic and pulmonary cardiovascular adjustments have been investigated for continuous exercise, it has not been done for IWET with exercise bouts near maximal work rate. METHODS In seven healthy subjects, the pulmonary hemodynamics have been studied by the aid of heart catheterization during a strenuous 30-min bicycle IWET where a 4-min work set at the first ventilatory threshold (VT1) alternated with a 1-min work set at the second ventilatory threshold (VT2). RESULTS During the IWET, cardiac output increased then remained stable with decreasing stroke volume and increasing heart rate, which became near maximal at the end of the test. Mean pulmonary arterial pressure increased from rest to the fifth minute of exercise and decreased significantly thereafter (P<0.01). An identical evolution was observed for mean systemic arterial pressure (SAP). CONCLUSION Pulmonary hemodynamics adapt well in healthy subjects during a strenuous IWET despite the performance of exercise bouts of near maximal intensity.

Fat and Carbohydrate Metabolism During Exercise in Phosphoglucomutase Type 1 Deficiency

CONTEXT Phosphoglucomutase type 1 (PGM1) deficiency is a rare metabolic myopathy in which symptoms are provoked by exercise. OBJECTIVE Because the metabolic block is proximal to the entry of glucose into the glycolytic pathway, we hypothesized that iv glucose could improve the exercise intolerance experienced by the patient. DESIGN This was an experimental intervention study. SETTING The study was conducted in an exercise laboratory. SUBJECTS Subjects were a 37-year-old man with genetically and biochemically verified PGM1 deficiency and 6 healthy subjects. INTERVENTIONS Cycle ergometer, peak and submaximal exercise (70% of peak oxygen consumption), and exercise with an iv glucose infusion tests were performed. MAIN OUTCOME MEASURES Peak work capacity and substrate metabolism during submaximal exercise with and without an iv glucose infusion were measured. RESULTS Peak work capacity in the patient was normal, as were increases in plasma lactate during peak and submaximal exercise. However, the heart rate decreased 11 beats minute⁻¹, the peak work rate increased 12.5%, and exercise was rated as being easier with glucose infusion in the patient. These results were in contrast to those in the control group, in whom no improvements occurred. In addition, the patient tended to become hypoglycemic during submaximal exercise. CONCLUSIONS This report characterizes PGM1 deficiency as a mild metabolic myopathy that has dynamic exercise-related symptoms in common with McArdle disease but no second wind phenomenon, thus suggesting that the condition clinically resembles other partial enzymatic defects of glycolysis. However, with glucose infusion, the heart rate decreased 11 beats min⁻¹, the peak work rate increased 12.5%, and exercise was considered easier by the patient.

Improving exercise capacity, 6 wk training tends to reduce circulating endothelin after heart transplantation

Abstract:  Short‐term survival is no longer the pivotal issue after heart transplantation but, most heart‐transplant (Htx) patients still present with increased circulating endothelin‐1 (ET) and reduced exercise capacity. ET‐1 limits both exercise‐induced vasodilation and blood flow redistribution toward acting muscles and might be accessible to training. This study was performed to investigate the effect of training on ET‐1 and whether an eventual training‐induced improvement in exercise capacity may be related to reduced baseline or exercise circulating ET‐1 in Htx patients. Five Htx patients performed a maximal bicycle exercise test and an endurance exercise test before and after a training program of 18 exercises sessions during 6 wk. ET‐1 was determined by radioimmunoassay at rest, end endurance exercise and 30 min recovery, before and after training. Training improved significantly Htxs maximal oxygen uptake (+13.1 ± 4.8%; p < 0.05) and also reduced significantly the endurance exercise‐induced heart rate increase. Resting ET‐1 was increased in Htx (5.98 ± 1.88 vs. 1.61 ± 0.25 pmol/L in controls; p < 0.01) but although ET‐1 modulation might participate in training‐induced beneficial effects, training failed to modulate either resting or exercise ET‐1 plasma level. Training‐induced improvement in exercise capacity might not mainly due to decreased ET‐1 after heart transplantation. Further supporting the usefulness of training, these preliminary data suggest that improved exercise capacity may not be mainly due to decreased ET‐1 in Htx patients. Further, larger scale studies will be needed to investigate whether an impaired nitric oxide pathway stimulation might explain such results and whether a longer training program can reduce local ET‐1, arising from working muscles after heart transplantation.

l-Arginine supplementation improves exercise capacity after a heart transplant

BACKGROUND Endothelial dysfunction is associated with the decreased exercise capacity observed in heart-transplant (HTx) recipients. L-arginine supplementation (LAS) stimulates the nitric oxide (NO) pathway and restores endothelial function. OBJECTIVE We compared exercise capacity in healthy subjects and HTx patients and investigated whether chronic LAS might improve exercise capacity and NO/endothelin balance after an HTx. DESIGN Clinical, echocardiographic, and exercise characteristics were measured in 11 control subjects and 22 HTx recipients. In a prospective, double-blind study, the 22 HTx recipients performed a 6-min exercise [6-min-walk test (6MWT)] and a maximal bicycle exercise test before and after a 6-wk period of placebo intake or LAS. Endothelial function was measured by analyzing blood NO metabolites, endothelin, and the resulting NO/endothelin balance. RESULTS Exercise capacity decreased after transplantation. Unlike with the placebo intake, 6 wk of LAS improved quality of life in HTx recipients (mean +/- SEM Minnesota Score: from 15.3 +/- 1.3 to 10.6 +/- 1.1; P < 0.001) and their submaximal exercise capacity. The distance walked during the 6MWT increased (from 525 +/- 20 to 580 +/- 20 m; P = 0.002), and the ventilatory threshold during the incremental test was delayed by 1.2 min (P = 0.01). Central factors such as resting stroke volume, systolic pulmonary arterial pressure, cardiac systolodiastolic functions, and heart-rate reserve were not modified, but LAS significantly increased the NO:endothelin ratio (from 2.49 +/- 0.38 to 3.31 +/- 0.39; P = 0.03). CONCLUSION Oral LAS may be a useful adjuvant therapeutic to improve quality of life and exercise tolerance in HTx recipients.

Can the Six-Minute Walk Test Predict Peak Oxygen Uptake in Men With Heart Transplant?

OBJECTIVE To determine whether the six-minute walk test (6MWT) might predict peak oxygen consumption (VO2peak) after heart transplantation. DESIGN Case-control prospective study. SETTING Public hospital. PARTICIPANTS Patients with heart transplant (n=22) and age-matched sedentary male subjects (n=13). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Exercise performance using a maximal exercise test, distance walked using the 6MWT, heart rate, and VO2peak. RESULTS Compared with controls, exercise performance was decreased in patients with heart transplant with less distance ambulated (516+/-13m vs 592+/-13m; P<.001) and a decrease in mean VO2peak (23.3+/-1.3 vs 29.6+/-1mL x min(-1) x kg(-1); P<.001). Patients with heart transplant showed an increased resting heart rate, a response delayed both at the onset of exercise and during recovery. However, the patients heart rate at the end of the 6MWT was similar to that obtained at the ventilatory threshold. The formula did not predict measured VO2, with a weak correlation observed between the six-minute walk distance and both VO2peak (r=.53; P<.01) and ventilatory threshold (r=.53; P<.01) after heart transplantation. Interestingly, when body weight was considered, correlations coefficient increased to .74 and .77, respectively (P<.001). CONCLUSIONS In heart transplant recipients, the 6MWT is a safe, practical, and submaximal functional test. The distance-weight product can be used as an alternative method for assessing the functional capacity after heart transplantation but cannot totally replace maximal VO2 determination.

Effect of eccentric versus concentric exercise training on mitochondrial function

Introduction: The effect of eccentric (ECC) versus concentric (CON) training on metabolic properties in skeletal muscle is understood poorly. We determined the responses in oxidative capacity and mitochondrial H2O2 production after eccentric (ECC) versus concentric (CON) training performed at similar mechanical power. Methods: Forty‐eight rats performed 5‐ or 20‐day eccentric (ECC) or concentric (CON) training programs. Mitochondrial respiration, H2O2 production, citrate synthase activity (CS), and skeletal muscle damage were assessed in gastrocnemius (GAS), soleus (SOL) and vastus intermedius (VI) muscles. Results: Maximal mitochondrial respiration improved only after 20 days of concentric (CON) training in GAS and SOL. H2O2 production increased specifically after 20 days of eccentric ECC training in VI. Skeletal muscle damage occurred transiently in VI after 5 days of ECC training. Conclusions: Twenty days of ECC versus CON training performed at similar mechanical power output do not increase skeletal muscle oxidative capacities, but it elevates mitochondrial H2O2 production in VI, presumably linked to transient muscle damage. Muscle Nerve 50: 803–811, 2014