Explained and unexplained variability of CO2-sensitivity in humans.
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Adult↗
Biomedical subjects
C M Spengler
Publications and source records attributed to C M Spengler.
Respiratory muscle endurance training in humans increases cycling endurance without affecting blood gas concentrations.
Isolated respiratory muscle endurance training (RMT) can prolong constant-intensity cycling performance. We tested whether RMT affects O2 supply during exercise, i.e. whether the partial pressure of oxygen in arterial blood (Pa,O2) and/or its oxygen saturation (SaO2) are higher during exercise after RMT than before. A group of 28 sedentary subjects were randomly assigned to either an RMT (n = 13) or a control group (n = 15). The RMT consisted of 40x30 min sessions of normocapnic hyperpnoea. The control group did not perform any training. Breathing and cycling endurance time as well as PaO2 and SaO2 during cycling at a constant intensity of 70% maximum power output were measured before and after the RMT or the control period. Mean breathing endurance increased significantly after RMT compared to control [RMT 5.2 (SD 2.9) vs 38.1 (SD 6.8) min, control 6.5 (SD 5.7) vs 6.4 (SD 7.6) min; P < 0.01], as did mean cycling endurance [RMT 35.6 (SD 11.9) vs 44.0 (SD 17.2) min, control 32.8 (SD 11.6) vs 31.4 (SD 14.4) min; P<0.05]. The RMT did not affect PaO2 which ranged from 11.6 to 12.3 kPa (87-92 mmHg), and SaO2 which ranged from 96% to 98% throughout all tests. In conclusion, RMT substantially increased breathing and cycling endurance in sedentary subjects. These changes, however, cannot be attributed to increased O2 supply, as neither PaO2 nor SaO2 were increased during exercise after RMT.
Adult↗
Respiratory muscle training increases cycling endurance without affecting cardiovascular responses to exercise.
We tested whether the increased cycling endurance observed after respiratory muscle training (RMT) in healthy sedentary humans was associated with a training-induced increase in cardiac stroke volume (SV) during exercise, similar to the known effect of endurance training. Thirteen subjects underwent RMT by normocapnic hyperpnea, nine underwent aerobic endurance training (cycling and/or running) and fifteen served as non-training controls. Training comprised 40 sessions performed within 15 weeks, where each session lasted 30 min. RMT increased cycling endurance at 70% maximal aerobic power (Wmax) by 24% [mean (SD) 35.6 (11.9) min vs 44.2 (17.6) min, P < 0.05], but SV at 60% Wmax was unchanged [94 (21) ml vs 93 (20) ml]. Aerobic endurance training increased both SV [89 (24) ml vs 104 (32) ml, P < 0.01] and cycling endurance [37.4 (12.8) min vs 52.6 (16.9) min, P < 0.01]. In the control group, no changes were observed in any of these variables. It is concluded that the increased cycling endurance that is observed after RMT is not due to cardiovascular adaptations, and that the results provide evidence for the role of the respiratory system as an exercise-limiting factor.
Adult↗
Chemoreceptive mechanisms elucidated by studies of congenital central hypoventilation syndrome.
Humans born with the condition of central hypoventilation during non-rapid eye movement sleep, termed congenital central hypoventilation syndrome (CCHS), invariably have absent or greatly diminished central hypercapnic ventilatory chemosensitivity. Genetic and pathological studies of CCHS may enable identification of the genes or areas of the central nervous system involved in the syndrome and thus implicated in central hypercapnic ventilatory chemosensitivity. Functional studies of CCHS permit a more quantitative assessment of the importance of ventilatory chemosensitivity in the regulation of breathing during wakefulness and sleep. The experimental evidence suggests that central hypercapnic ventilatory chemosensitivity is crucial in regulating alveolar ventilation during non-rapid eye movement sleep but not during rapid eye movement sleep or during many of the behaviors occurring during wakefulness. Presumably, other neural drives to breathe supervene to enable adequate ventilation. However, although physiological studies in CCHS subjects have been greatly instructive, their accurate interpretation will have to await future determination of the potential genetic and/or neuroanatomic basis of the syndrome.
Chemoreceptor Cells↗
An endogenous circadian rhythm of respiratory control in humans.
Many physiological and behavioural functions have circadian rhythms - endogenous oscillations with a period of approximately 24 h that can occur even in the absence of sleep. We determined whether there is an endogenous circadian rhythm in breathing, metabolism and ventilatory chemosensitivity in humans. Ten healthy, adult males were studied throughout 4 days in a stable laboratory environment. After two initial baseline days (16 h wakefulness plus 8 h sleep) that served to achieve a steady state, subjects were studied under constant behavioural and environmental conditions throughout 41 h of wakefulness. Ventilation, metabolism and the magnitude of the hypercapnic ventilatory response (HCVR) were measured every 2 h. Individuals' data were aligned according to circadian phase (core body temperature minimum; CBTmin) and averaged. In the group average data, there was a significant and large amplitude circadian variation in HCVR slope (average of +/-0.4 l min-1 mmHg-1; corresponding to +/-12.1 % of 24 h mean), and a smaller amplitude rhythm in the HCVR x-axis intercept (average of +/-1.1 mmHg; +/-2.1 % of 24 h mean). Despite a significant circadian variation in metabolism (+/-3.2 % of 24 h mean), there were no detectable rhythms in tidal volume, respiratory frequency or ventilation. This small discrepancy between metabolism and ventilation led to a small but significant circadian variation in end-tidal PCO2 (PET,CO2; +/-0.6 mmHg; +/-1.5 % of 24 h mean). The circadian minima of the group-averaged respiratory variables occurred 6-8 h earlier than CBTmin, suggesting that endogenous changes in CBT across the circadian cycle have less of an effect on respiration than equivalent experimentally induced changes in CBT. Throughout these circadian changes, there were no correlations between HCVR parameters (slope or x-axis intercept) and either resting ventilation or resting PET,CO2. This suggests that ventilation and PET,CO2 are little influenced by central chemosensory respiratory control in awake humans even when at rest under constant environmental and behavioural conditions. The characteristic change in PET,CO2 during non-rapid eye movement sleep was shown to be independent of circadian variations in PET,CO2, and probably reflects a change from predominantly behavioural to predominantly chemosensory respiratory control. This study has documented the existence and magnitude of circadian variations in respiration and respiratory control in awake humans for the first time under constant behavioural and environmental conditions. These results provide unique insights into respiratory control in awake humans, and highlight the importance of considering the phase of the circadian cycle in studies of respiratory control.
Adult↗
Breathing pattern and exercise endurance time after exhausting cycling or breathing.
The aim of the present study was to investigate whether the changes in breathing pattern that frequently occur towards the end of exhaustive exercise (i.e., increased breathing frequency, fb, with or without decreased tidal volume) may be caused by the respiratory work itself rather than by leg muscle work. Eight healthy, trained subjects performed the following three sessions in random order: (A) two sequential cycling endurance tests at 78% peak O2 consumption (VO2peak) to exhaustion (A1, A2); (B) isolated, isocapnic hyperpnea (B1) at a minute ventilation (VE) and an exercise duration similar to that attained during a preliminary cycling endurance test at 78% VO2peak, followed by a cycling endurance test at 78% VO2peak (B2); (C) isolated, isocapnic hyperpnea (C1) at a VE at least 20% higher than that of the preliminary cycling test and the same exercise duration as the preliminary cycling test, followed by a cycling endurance test at 78% VO2peak (C2). Neither of the two isocapnic hyperventilation tasks (B1 or C1) affected either the breathing pattern or the endurance times of the subsequent cycling tests. Only cycling test A2 was significantly shorter [mean (SD) 26.5 (8.3) min] than tests A1 [41.0(9.0) min], B2 [41.9 (6.0) min], and C2 [42.0 (7.5) min]. In addition, compared to test A1, only the breathing pattern of test A2 was significantly different [i.e., VE: + 10.5 (7.6) 1 min(-1), and fb: + 12.1 (8.5) breaths min(-1)], in contrast to the breathing patterns of cycling tests B2 [VE: -2.5 (6.2) 1 min(-1), f(b): +0.2 (3.6) breaths min(-1)] and C2 [VE: -3.0 (7.0) 1 min(-1), fb: +0.6 (6.1) breaths min(-1)]. In summary, these results suggest that the changes in breathing pattern that occur towards the end of an exhaustive exercise test are a result of changes in the leg muscles rather than in the respiratory muscles themselves.
Adult↗
Influence of endurance exercise on respiratory muscle performance.
PURPOSE: During high-intensity, exhaustive, constant-load exercise above 85% of maximal oxygen consumption, the diaphragm of healthy subjects can fatigue. Although a decrease in trans-diaphragmatic pressure is the most objective measure of diaphragmatic fatigue, possible extra-diaphragmatic muscle fatigue would not be detected by this method. The aim of the present study was to investigate the impact of exhaustive, constant-load cycling exercise at different intensities on global respiratory performance determined by the time to exhaustion while breathing against a constant resistance. METHODS: Ten healthy, male subjects performed an exhaustive cycling endurance test at 65, 75, 85, and 95% of peak oxygen consumption (VO2peak). Before cycling (to) as well as at 10 min (t10) and 45 min (t45) after cycling, respiratory performance was determined. RESULTS: Breathing endurance was equivalently reduced after exhaustive cycling at either 65% (8.4 +/- 4.1 min [t0] vs 3.9 +/- 2.8 min [t10]), 75% (9.9 +/- 6.1 vs 4.4 +/- 2.8 min), 85% (9.3 +/- 6.0 vs 3.8 +/- 2.9 min), or 95% VO2peak (8.5 +/- 5.1 vs 4.0 +/- 2.5 min) and, therefore, was independent of exercise intensity. CONCLUSION: This result contradicts previous findings, possibly due to the fact that extra-diaphragmatic muscles are tested in addition to the diaphragm during resistive breathing.
Adult↗
Sleep deprivation per se does not decrease the hypercapnic ventilatory response in humans.
Several studies have found that sleep deprivation reduces the hypercapnic ventilatory response (HCVR). Such results may have been affected by uncontrolled activities or environmental influences during the sleep deprivation period. The current study determined the "pure" effect of sleep deprivation on respiratory control under strictly controlled behavioral and environmental conditions. After 2 d of acclimation in the laboratory, 10 subjects maintained wakefulness (confirmed by EEG), a constant semirecumbent posture, ate regular small meals, had constant interaction with experimenters, and stayed in an environment with constant low light (10 lux) and constant room temperature for 41 consecutive hours. Measurements of HCVR, resting ventilation, V O(2) and V CO(2) were performed every 2 h. Comparisons were made of six pairs of measurements, with each pair separated by 24 h of sleep deprivation. None of the respiratory variables changed significantly with 24 h of sleep deprivation. Mean HCVR increased by 17% with sleep deprivation (3.12 versus 3.54 L x min(-1) x mm Hg(-1); not significant). These results show that sleep deprivation per se does not reduce the sensitivity of central chemoreceptors nor change resting ventilation or metabolism. The reduced HCVR after sleep loss found in previous studies may have been affected by uncontrolled activities or environmental influences during sleep deprivation periods.
Adult↗
Endogenous circadian rhythm of pulmonary function in healthy humans.
Numerous studies have demonstrated a diurnal rhythm in indices of pulmonary function in both healthy subjects and subjects with asthma, with minima occurring during the night. To determine whether such diurnal changes are caused by an endogenous circadian rhythm or by diurnal alterations in behavior or the environment, we measured indices of pulmonary function throughout a "constant routine" protocol designed to unmask underlying circadian rhythms. After two acclimation days in the laboratory, 10 healthy adults maintained relaxed wakefulness in a semirecumbent posture in a constant environment with low light (10 lux) for 41 h. Measurements of FEV(1), FEVC, PEF, blood cortisol, and core body temperature (CBT) were performed every 2 h. Results of cosinor analysis of group data aligned to CBT circadian minimum revealed significant circadian variations in FEV(1) and FEV(1)/FEVC, cortisol, and CBT, and lack of significant circadian variations in FEVC and PEF. The ranges (peak to trough) of mean circadian changes in spirometric variables were 2. 0-3.2% of the mesor. The circadian minima of all variables occurred within the usual sleep period (although subjects remained awake). Because of differences in phase relationships between CBT and pulmonary function among subjects, the circadian rhythms within subjects were generally larger than the group average circadian changes, being significant for FEV(1)/FEVC in 5 of 10 subjects and for PEF in 6 of 10 subjects. Sleep deprivation (24 h) failed to cause a significant change in any pulmonary function variable (when controlled for circadian phase). Thus, endogenous circadian rhythms contribute to diurnal changes in pulmonary function in healthy subjects.
Adult↗
Respiratory muscle endurance training in chronic obstructive pulmonary disease: impact on exercise capacity, dyspnea, and quality of life.
Inspiratory muscle training may have beneficial effects in certain patients with chronic obstructive pulmonary disease (COPD). Because of the lack of a home training device, normocapnic hyperpnea has rarely been used as a training mode for patients with COPD, and is generally considered unsuitable to large-scale application. To study the effects of hyperpnea training, we randomized 30 patients with COPD and ventilatory limitation to respiratory muscle training (RMT; n = 15) with a new portable device or to breathing exercises with an incentive spirometer (controls; n = 15). Both groups trained twice daily for 15 min for 5 d per week for 8 wk. Training-induced changes were significantly greater in the RMT than in the control group for the following variables: respiratory muscle endurance measured through sustained ventilation (+825 +/- 170 s [mean +/- SEM] versus -27 +/- 61 s, p < 0.001), inspiratory muscle endurance measured through incremental inspiratory threshold loading (+58 +/- 10 g versus +21.7 +/- 9.5 g, p = 0.016), maximal expiratory pressure (+20 +/- 7 cm H(2)O versus -6 +/- 6 cm H(2)O, p = 0.009), 6-min walking distance (+58 +/- 11 m versus +11 +/- 11 m, p = 0.002), V O(2peak) (+2.5 +/- 0.6 ml/kg/min versus -0.3 +/- 0.9 ml/kg/min, p = 0.015), and the SF-12 physical component score (+9.9 +/- 2.7 versus +1.8 +/- 2.4, p = 0.03). Changes in dyspnea, maximal inspiratory pressure, treadmill endurance, and the SF-12 mental component score did not differ significantly between the RMT and control groups. In conclusion, home-based respiratory muscle endurance training with the new device used in this study is feasible and has beneficial effects in subjects with COPD and ventilatory limitation.
Aged↗
Decreased exercise blood lactate concentrations after respiratory endurance training in humans.
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 (VO2) 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 VO2 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 x 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 x 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.
Adult↗
Noninvasive measurement of respiratory muscle performance after exhaustive endurance exercise.
The use of noninvasive techniques to measure respiratory muscle performance after different types of endurance exercise has not been entirely successful, as the results have not consistently indicated diminished performance for similar types of exercise. The aim of the present study was 1) to compare different, noninvasive methods to assess respiratory muscle performance before and after an exhaustive cycling endurance test (which has previously been shown to induce diaphragmatic fatigue) and 2) to determine which of the tests best reflect published results of measurements of diaphragmatic fatigue. Twelve healthy subjects participated in the study and performed three different test series in a random order on three different days. These tests were performed before, and 5, 40 and 75 min after an exhausting task (a cycling endurance run at 85% of maximal oxygen uptake (V'O2,max)). The tests of the three test series were 1) breathing against a constant inspiratory resistance to task failure, 2) determination of 12-min sustained ventilatory capacity, and 3) spirometric and maximal inspiratory and expiratory mouth pressure measurements. The only measurement that was affected by exhaustive cycling was the time to task failure breathing against inspiratory resistance. It was significantly reduced from (mean+/-sD) 364+/-88 s before exercise to 219+/-122 s at 5 min after cessation of exercise. It is concluded that the constant-load resistive breathing test to task failure is the only noninvasive respiratory muscle performance test evaluated in this study which shows a decrease in respiratory muscle performance after exhaustive endurance exercise.
Adult↗
Respiratory sensations during heavy exercise in subjects without respiratory chemosensitivity.
Breathlessness arises from increased medullary respiratory center activity projecting to the forebrain (respiratory corollary discharge hypothesis). Subjects with congenital central hypoventilation syndrome (CCHS) lack the normal hyperpnea and breathlessness during hypercapnia. The corollary discharge hypothesis predicts that if CCHS subjects have normal hyperpnea during exercise, they will experience normal breathlessness during exercise. To test this, we studied four CCHS subjects and six matched controls during an exhausting constant-load cycling test requiring substantial anaerobiosis. CCHS subjects rated significantly less breathlessness at the end of the test than controls, but ventilation (index of respiratory corollary discharge) was also somewhat lower in CCHS (not significant). In both groups, breathlessness increased disproportionately more than ventilation towards the end of exercise. These data failed to disprove the corollary discharge hypothesis of breathlessness, but do suggest that the relationship between ventilation and breathlessness is non-linear and/or that projections of chemoreceptor afferents to the forebrain (presumed lacking in CCHS) is one source of breathlessness in normals.
Adolescent↗
Self-control and external control of mechanical ventilation give equal air hunger relief.
Elevated end-tidal partial pressure of CO2 (PET(CO2)) causes air hunger; this sensation becomes intense with a relatively small rise in PET(CO2) if ventilation is held constant. Spontaneously breathing subjects increase ventilation in response to CO2, thereby greatly diminishing air hunger. In healthy subjects and ventilator-dependent patients, experimenter-induced increases in ventilator tidal volume (VT) relieve air hunger even if PET(CO2) is kept elevated. We addressed two questions: (1) Can paralyzed, ventilator-dependent patients use the sensation of air hunger to effectively control ventilator VT using nonrespiratory motor pathways; and (2) Do subjects obtain more relief when in control of their own ventilator? Four subjects were trained to increase ventilator VT using a mouth-operated switch. Subjects' ratings of air hunger intensity in response to elevated PET(CO2) were compared during three conditions: (1) constant VT; (2) subject-controlled VT; and (3) experimenter-controlled VT. When given control of their ventilator, all subjects increased VT in response to increased PET(CO2), thereby relieving air hunger. Air hunger relief was similar when the experimenter mimicked these VT changes. These results suggest that: (1) ventilator-dependent patients can use sensation, conscious decisions, and nonrespiratory motor pathways to achieve an appropriate respiratory response to increased PCO2 and (2) control of one's own ventilation is unimportant in these circumstances.
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Modulation of the ventilatory increase at the onset of exercise in humans.
The fast initial increase in ventilation at the start of exercise is generally assumed to be of reflex origin (exercising limbs) and/or caused by a 'feedforward' mechanism increasing breathing via brainstem respiratory centres or cortical areas controlling respiratory muscles. We wanted to test whether this ventilatory increase is in part a learned response which can be modified. Eleven subjects did two 20 min low-intensity arm-cranking exercise bouts on eight different days. Seven subjects were assigned to the experimental group which performed exercise paired with an 1.5 L external dead space. Before and after their eight exercise 'training'-days, these subjects did the same exercise without dead space. At the beginning of the first post-training exercise test (without dead space), the ventilatory increase at the start of exercise (sum of the first four breaths) was significantly increased (31.1 +/- 4.1 L . min-1) compared to the pre-training test session (24.4 +/- 3.9 L . min-1). No significant change was observed in the control group. We conclude that part of the ventilatory increase at the start of exercise can be modulated and might possibly be a learned response.
Adult↗
The role of central command in ventilatory control during static exercise.
The role of central command in the respiratory response to 15 min of rhythmic-static (isometric) exercise was studied in humans. Voluntary exercise (VE) was compared with electrically induced exercise (EE) at three different work intensities, i.e. 5%, 15% and 25% of maximal voluntary contraction. A group of 12 volunteers participated in the study and each of them performed six sessions. A session consisted of at least 5 min rest, 15 min rhythmic-static single leg exercise (4 s contraction/12 s relaxation) and at least 5 min recovery. Force, minute ventilation (VE) and oxygen uptake (VO2) were measured. In EE, both VE and VO2 increased continuously during the entire exercise period after an initial rapid increase at all three work intensities. Correlation between VE and VO2 was highly significant during EE. During all three work intensities of VE, VE and VO2 achieved a steady-state after the initial increase. During VE, VE did not correlate as closely with VO2 as during EE. All these findings indicate that central command was not imperative for an adequate ventilatory response to exercise within all three work intensities investigated. Without the influence of central command, correlation between VE and VO2 was even better than during VE.
Adult↗