Urs Boutellier

The respiratory system as an exercise limiting factor in normal sedentary subjects

SummaryThe present study was undertaken to investigate the respiratory system as an exercise limiting factor. Breathing and cycle endurance (i.e. the time until exhaustion at a given performance level) as well as physical working capacity 170 (i.e. the exercise intensity corresponding to a heart rate of 170 beats -min−1 on a cycle ergometer) were determined in four healthy sedentary subjects. Subsequently, the subjects trained their respiratory system for 4 weeks by breathing daily about 901 · min−1 for 30 min. Otherwise they continued their sedentary lifestyle. Immediately after the respiratory training and 18 months later, all performance tests carried out at the beginning of the study were repeated. The respiratory training increased breathing endurance from 4.2 (SD 1.9) min to 15.3 (SD 3.8) min. Cycle endurance was improved from 26.8 (SD 5.9) min to 40.2 (SD 9.2) min whereas physical working capacity 170 remained essentially the same. During the endurance cycling test in the respiratory untrained state, the subjects continuously increased their ventilation up to hyperventilation [ventilation at exhaustion = 96.9 (SD 23.6) 1 · min−1] while after the respiratory training they reached a respiratory steady-state without hyperventilation [ventilation at exhaustion = 63.3 (SD 14.5) 1 · min−1]. The absence of this marked hyperventilation was the cause of the impressive increase of cycle endurance in normal sedentary subjects after respiratory training. The effects gained by the respiratory training were completely lost after 18 months. Our results indicated that the respiratory system was an exercise limiting factor during an endurance test in normal sedentary subjects.

New fundamental resistance exercise determinants of molecular and cellular muscle adaptations.

Physical activity relies on muscular force. In adult skeletal muscle, force results from the contraction of postmitotic, multinucleated myofibres of different contractile and metabolic properties. Myofibres can adapt to (patho-)physiological conditions of altered functional demand by radial growth, longitudinal growth, and regulation of fibre type functional gene modules. The adaptation’s specificity depends on the distinct molecular and cellular events triggered by unique combinations of conditional cues. In order to derive effective and tailored exercise prescriptions, it must be determined (1) which mechano-biological condition leads to what molecular/cellular response, and (2) how this molecular/cellular response relates to the structural, contractile, and metabolic adaptation. It follows that a thorough mechano-biological description of the loading condition is imperative. Unfortunately, the definition of (resistance) exercise conditions in the past and present literature is insufficient. It is classically limited to load magnitude, number of repetitions and sets, rest in-between sets, number of interventions/week, and training period. In this review, we show why the current description is insufficient, and identify new determinants of quantitative and/or qualitative effects on skeletal muscle with respect to resistance exercise in healthy, adult humans. These new mandatory determinants comprise the fractional and temporal distribution of the contraction modes per repetition, duration of one repetition, rest in-between repetitions, time under tension, muscular failure, range of motion, recovery time, and anatomical definition. We strongly recommend to standardise the design and description of all future resistance exercise investigations by using the herein proposed set of 13 mechano-biological determinants (classical and new ones).

Decreased exercise blood lactate concentrations after respiratory endurance training in humans.

Abstract For many years, it was believed that ventilation does not limit performance in healthy humans. Recently, however, it has been shown that inspiratory muscles can become fatigued during intense endurance exercise and decrease their exercise performance. Therefore, it is not surprising that respiratory endurance training can prolong intense constant-intensity cycling exercise. To investigate the effects of respiratory endurance training on blood lactate concentration and oxygen consumption (V˙O2) during exercise and their relationship to performance, 20 healthy, active subjects underwent 30 min of voluntary, isocapnic hyperpnoea 5 days a week, for 4 weeks. Respiratory endurance tests, as well as incremental and constant-intensity exercise tests on a cycle ergometer, were performed before and after the 4-week period. Respiratory endurance increased from 4.6 (SD 2.5) to 29.1 (SD 4.0) min (P < 0.001) and cycling endurance time was prolonged from 20.9 (SD 5.5) to 26.6 (SD 11.8) min (P < 0.01) after respiratory training. The V˙O2 did not change at any exercise intensity whereas blood lactate concentration was lower at the end of the incremental [10.4 (SD 2.1) vs 8.8 (SD 1.9) mmol · l−1, P < 0.001] as well as at the end of the endurance exercise [10.4 (SD 3.6) vs 9.6 (SD 2.7) mmol · l−1, P < 0.01] test after respiratory training. We speculate that the reduction in blood lactate concentration was most likely caused by an improved lactate uptake by the trained respiratory muscles. However, reduced exercise blood lactate concentrations per se are unlikely to explain the improved cycling performance after respiratory endurance training.

Impact of pulmonary system limitations on locomotor muscle fatigue in patients with COPD

We examined the effects of respiratory muscle work [inspiratory (W(r-insp)); expiratory (W(r-exp))] and arterial oxygenation (Sp(O(2))) on exercise-induced locomotor muscle fatigue in patients with chronic obstructive pulmonary disease (COPD). Eight patients (FEV, 48 +/- 4%) performed constant-load cycling to exhaustion (Ctrl; 9.8 +/- 1.2 min). In subsequent trials, the identical exercise was repeated with 1) proportional assist ventilation + heliox (PAV); 2) heliox (He:21% O(2)); 3) 60% O(2) inspirate (hyperoxia); or 4) hyperoxic heliox mixture (He:40% O(2)). Five age-matched healthy control subjects performed Ctrl exercise at the same relative workload but for 14.7 min ( approximately best COPD performance). Exercise-induced quadriceps fatigue was assessed via changes in quadriceps twitch force (Q(tw,pot)) from before to 10 min after exercise in response to supramaximal femoral nerve stimulation. During Ctrl, absolute workload (124 +/- 6 vs. 62 +/- 7 W), W(r-insp) (207 +/- 18 vs. 301 +/- 37 cmH(2)O x s x min(-1)), W(r-exp) (172 +/- 15 vs. 635 +/- 58 cmH(2)O x s x min(-1)), and Sp(O(2)) (96 +/- 1% vs. 87 +/- 3%) differed between control subjects and patients. Various interventions altered W(r-insp), W(r-exp), and Sp(O(2)) from Ctrl (PAV: -55 +/- 5%, -21 +/- 7%, +6 +/- 2%; He:21% O(2): -16 +/- 2%, -25 +/- 5%, +4 +/- 1%; hyperoxia: -11 +/- 2%, -17 +/- 4%, +16 +/- 4%; He:40% O(2): -22 +/- 2%, -27 +/- 6%, +15 +/- 4%). Ten minutes after Ctrl exercise, Q(tw,pot) was reduced by 25 +/- 2% (P < 0.01) in all COPD and 2 +/- 1% (P = 0.07) in healthy control subjects. In COPD, DeltaQ(tw,pot) was attenuated by one-third after each interventional trial; however, most of the exercise-induced reductions in Q(tw,pot) remained. Our findings suggest that the high susceptibility to locomotor muscle fatigue in patients with COPD is in part attributable to insufficient O(2) transport as a consequence of exaggerated arterial hypoxemia and/or excessive respiratory muscle work but also support a critical role for the well-known altered intrinsic muscle characteristics in these patients.

Spinal opioid receptor‐sensitive muscle afferents contribute to the fatigue‐induced increase in intracortical inhibition in healthy humans

We investigated the influence of spinal opioid receptor‐sensitive muscle afferents on cortical changes following fatiguing unilateral knee‐extensor exercise. On separate days, seven subjects performed an identical five sets of intermittent isometric right‐quadriceps contractions, each consisting of eight submaximal contractions [63 ± 7% maximal voluntary contraction (MVC)] and one MVC. The exercise was performed following either lumbar interspinous saline injection or lumbar intrathecal fentanyl injection blocking the central projection of spinal opioid receptor‐sensitive lower limb muscle afferents. To quantify exercise‐induced peripheral fatigue, quadriceps twitch force (Qtw,pot) was assessed via supramaximal magnetic femoral nerve stimulation before and after exercise. Motor evoked potentials and cortical silent periods (CSPs) were evaluated via transcranial magnetic stimulation of the motor cortex during a 3% MVC pre‐activation period immediately following exercise. End‐exercise quadriceps fatigue was significant and similar in both conditions (ΔQtw,pot−35 and −39% for placebo and fentanyl, respectively; P= 0.38). Immediately following exercise on both days, motor evoked potentials were similar to those obtained prior to exercise. Compared with pre‐exercise baseline, CSP in the placebo trial was 21 ± 5% longer postexercise (P < 0.01). In contrast, CSP following the fentanyl trial was not significantly prolonged compared with the pre‐exercise baseline (6 ± 4%). Our findings suggest that the central effects of spinal opioid receptor‐sensitive muscle afferents might facilitate the fatigue‐induced increase in CSP. Furthermore, since the CSP is thought to reflect inhibitory intracortical interneuron activity, which may contribute to central fatigue, our findings imply that spinal opioid receptor‐sensitive muscle afferents might influence central fatigue by facilitating intracortical inhibition.

Limitation of physical performance in a muscle fatiguing handgrip exercise is mediated by thalamo-insular activity

In this study, we investigated central/supraspinal processes mediating cessation of a muscle fatiguing exercise. Fifteen male subjects performed 39 intermittent, isometric handgrip contractions (13 s on, 5–6 s off) with the dominant right hand while brain activation was assessed by means of functional magnetic resonance imaging (fMRI). An adaptive, partly stochastic protocol was designed such that in approximately 50% of the contraction trials the required force could not be held until the end of the trial (task failure trial). Trials performed in compliance with the force requirements (succeeded trial) were compared with task failure trials concerning neural activity during a small time window before task failure occurred. The data revealed significantly increased activation contralaterally in both the mid/anterior insular cortex and the thalamus during the investigated time window in the case of subsequent task failure. In accordance with other studies investigating sensations that alert the organism to urgent homeostatic imbalance such as air hunger, hunger for food, and pain, we assume that an increased thalamo‐insular activation in the context of a fatigue‐induced handgrip exercise could reflect increased homeostatic disturbance in the exercising muscle and may be of essential importance by mediating task failure to maintain the integrity of the organism. Hum Brain Mapp, 2011.

Fatigue-induced increase in intracortical communication between mid/anterior insular and motor cortex during cycling exercise.

In the present study, intracortical communication between mid/anterior insular and motor cortex was investigated during a fatiguing cycling exercise. From 16 healthy male subjects performing a constant‐load test at 60% peak oxygen consumption (VO2peak) until volitional exhaustion, electroencephalography data were analysed during repetitive, artefact‐free periods of 1‐min duration. To quantify fatigue‐induced intracortical communication, mean intra‐hemispheric lagged phase synchronization between mid/anterior insular and motor cortex was calculated: (i) at the beginning of cycling; (ii) at the end of cycling; and (iii) during recovery cycling. Results revealed significantly increased lagged phase synchronization at the end of cycling, which returned to baseline during recovery cycling after subjects’ cessation of exercise. Following previous imaging studies reporting the mid/anterior insular cortex as an essential instance processing a variety of sensory stimuli and signalling forthcoming physiological threat, our results provide further evidence that during a fatiguing exercise this structure might not only integrate and evaluate sensory information from the periphery, but also act in communication with the motor cortex. To the best of our knowledge, this is the first study to empirically demonstrate that muscle fatigue leads to changes in interaction between structures of a brain’s neural network.

Effect of respiratory muscle endurance training on respiratory sensations, respiratory control and exercise performance: A 15-year experience

Respiratory muscle endurance training (RMET) can improve respiratory muscle endurance as well as cycling and swimming endurance. Whether these improvements are caused by reduced perception of adverse respiratory sensations and/or a change in ventilatory output remains unclear. We re-analysed nine (five randomized controlled) RMET studies performed in our laboratory. One hundred and thirty-five healthy subjects completed either RMET [i.e. an average of 12.4+/-4.9h (median 10; range 10-25) of normocapnic hyperpnoea at 60-85% of maximal voluntary ventilation achieved during 27+/-11 sessions (median 20; range 20-50) of 29+/-4min (median 30; range 15-30) duration over 6.5+/-4.2 weeks (median 4; range 4-15), n=90] or no RMET (CON, n=45). Before and after RMET/CON, respiratory ( approximately 70% MVV) and cycling (70-85% maximal power) endurance were tested. RMET increased both respiratory and cycling endurance, reduced perception of breathlessness and respiratory exertion during volitional and exercise-induced hyperpnoea, and slightly increased ventilation at identical workloads. Decreased respiratory sensations did not correlate with improved cycling endurance. Changes in ventilation correlated with changes in cycling endurance in both groups. We conclude that reduced adverse respiratory sensations after RMET are unlikely to cause the improvements in cycling endurance, that the level of ventilation seems to affect cycling endurance and that additional factors must contribute to the improvements in cycling endurance after RMET.

Effects of atropine and propranolol on the respiratory, circulatory, and ECG responses to high altitude in man

SummaryIn order to anlayse the respiratory, cardiovascular, and ECG responses to acute hypoxic hypoxia, three experimental series were carried out in a randomized manner on 11 healthy, unacclimatized volunteers at rest during standardized stepwise exposure to 6000 m (PAO2 35.2±2.9 mmHg/4.7±0.4 kPa) in a low-pressure chamber a) without (control), b) with propranolol, and c) with atropine combined with propranolol. The results, show that hypoxic hyperventilation and alveolar gases are not affected by activation of the sympatho-adrenal axis or by parasympathetic withdrawal. Sympathetic activity, however, increases heart rate, stroke volume (pulse pressure), estimated cardiac output and systolic blood pressure, whereas decreased parasympathetic activity increases heart rate and estimated cardiac output, but lowers stroke volume. The fall in peripheral resistance, observed during progressive hypoxia in all three groups, is thought to be due to hypoxia-induced depression of the vasomotor center. At altitude catecholamine secretion and vagal withdrawal synergistically account in the ECG for the R-R shortening, the relative Q-T lengthening, the elevation of the P wave and the ST-T flattening. Probable direct hypoxic effects on the heart are the increase in P-Q duration and the minor but still significant depression of the T wave. It is concluded that at altitude increased sympatho-adrenal and decreased parasympathetic activity is without effect on hypoxic hyperventilation, but accounts for most of the cardiovascular and ECG changes. Diminution of sympathetic activity and imminent vagotonia arising after acute ascent to 6000 m probably reflect hypoxia of the central nervous system.

Electric pulse stimulation of cultured murine muscle cells reproduces gene expression changes of trained mouse muscle.

Adequate levels of physical activity are at the center of a healthy lifestyle. However, the molecular mechanisms that mediate the beneficial effects of exercise remain enigmatic. This gap in knowledge is caused by the lack of an amenable experimental model system. Therefore, we optimized electric pulse stimulation of muscle cells to closely recapitulate the plastic changes in gene expression observed in a trained skeletal muscle. The exact experimental conditions were established using the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) as a marker for an endurance-trained muscle fiber. We subsequently compared the changes in the relative expression of metabolic and myofibrillar genes in the muscle cell system with those observed in mouse muscle in vivo following either an acute or repeated bouts of treadmill exercise. Importantly, in electrically stimulated C2C12 mouse muscle cells, the qualitative transcriptional adaptations were almost identical to those in trained muscle, but differ from the acute effects of exercise on muscle gene expression. In addition, significant alterations in the expression of myofibrillar proteins indicate that this stimulation could be used to modulate the fiber-type of muscle cells in culture. Our data thus describe an experimental cell culture model for the study of at least some of the transcriptional aspects of skeletal muscle adaptation to physical activity. This system will be useful for the study of the molecular mechanisms that regulate exercise adaptation in muscle.