The contribution of "resting" body muscles to the slow component of pulmonary oxygen uptake during high-intensity cycling.

Oxygen uptake (VO2) kinetics during moderate constant-workrate (WR) exercise (>lactate-threshold (θL)) are well described as exponential. AboveθL, these kinetics are more complex, consequent to the development of a delayed slow component (VO2sc), whose aetiology remains controversial. To assess the extent of the contribution to the VO2sc from arm muscles involved in postural stability during cycling, six healthy subjects completed an incremental cycle-ergometer test to the tolerable limit for estimation of θL and determination of peak VO2. They then completed two constant-WR tests at 90% of θL and two at 80% of ∆ (difference between θL and VO2peak). Gas exchange variables were derived breath-by-breath. Local oxygenation profiles of the vastus lateralis and biceps brachii muscles were assessed by near-infrared spectroscopy, with maximal voluntary contractions (MVC) of the relevant muscles being performed post-exercise to provide a frame of reference for normalising the exercise-related oxygenation responses across subjects. Above supra-θL, VO2 rose in an exponential-like fashion ("phase 2), with a delayed VO2sc subsequently developing. This was accompanied by an increase in [reduced haemoglobin] relative to baseline (∆[Hb]), which attained 79 ± 13 % (mean, SD) of MVC maximum in vastus lateralis at end-exercise and 52 ± 27 % in biceps brachii. Biceps brachii ∆[Hb] was significantly correlated with VO2 throughout the slow phase. In contrast, for sub- L exercise, VO2 rose exponentially to reach a steady state with a more modest increase in vastus lateralis ∆[Hb] (30 ± 11 %); biceps brachii ∆[Hb] was minimally affected (8 ± 2 %). That the intramuscular O2 desaturation profile in biceps brachii was proportional to that for VO2sc during supra-θL cycle ergometry is consistent with additional stabilizing arm work contributing to the VO2sc.

Oxygen uptake kinetics during incremental- and decremental-ramp cycle ergometry.

The pulmonary oxygen uptake (VO2) response to incremental-ramp cycle ergometry typically demonstrates lagged-linear first-order kinetics with a slope of ~10-11 ml·min(-1)·W(-1), both above and below the lactate threshold (θL), i.e. there is no discernible VO2 slow component (or "excess" VO2) above θL. We were interested in determining whether a reverse ramp profile would yield the same response dynamics. Ten healthy males performed a maximum incremental -ramp (15-30 W·min(-1), depending on fitness). On another day, the work rate (WR) was increased abruptly to the incremental maximum and then decremented at the same rate of 15-30 W.min(-1) (step-decremental ramp). Five subjects also performed a sub-maximal ramp-decremental test from 90% of θL. VO2 was determined breath-by-breath from continuous monitoring of respired volumes (turbine) and gas concentrations (mass spectrometer). The incremental-ramp VO2-WR slope was 10.3 ± 0.7 ml·min(-1)·W(-1), whereas that of the descending limb of the decremental ramp was 14.2 ± 1.1 ml·min(-1)·W(-1) (p < 0.005). The sub-maximal decremental-ramp slope, however, was only 9. 8 ± 0.9 ml·min(-1)·W(-1): not significantly different from that of the incremental-ramp. This suggests that the VO2 response in the supra-θL domain of incremental-ramp exercise manifest not actual, but pseudo, first-order kinetics. Key pointsThe slope of the decremental-ramp response is appreciably greater than that of the incremental.The response dynamics in supra-θL domain of the incremental-ramp appear not to manifest actual first-order kinetics.The mechanisms underlying the different dynamic response behaviour for incremental and decremental ramps are presently unclear.

Kinetics of the ventilatory and metabolic responses to moderate-intensity exercise in humans following prior exercise-induced metabolic acidaemia.

As the time constant of the phase 2 (ø2) ventilatory response (tauV'(E)) to moderate exercise (< lactate threshold, thetaL) is reduced by exogenous procedures that augment peripheral (carotid) chemosensitivity (hypoxia; chronic metabolic acidaemia), we examined whether an acute endogenous metabolic acidaemia had a similar effect. Six subjects completed two tests (A, B), each comprising two 6-min bouts separated by a 6-min "0" W recovery: A:- 90% thetaL, 90% thetaL; B:- supra-thetaL (50% between thetaL and peak V'O2), 90% thetaL. For Protocol A, the bout 2 sub-thetaL tauV'E was similar to bout 1. However, for Protocol B, where the initial supra-thetaL metabolic acidaemia was still evident at the end of the subsequent sub-thetaL bout, the sub-thetaL tauV'E was shorter; tauV'E/tauV'O2 and tauV'E/tauV'CO2 were reduced; and the transient end-tidal PO2undershoot was less marked. We conclude that an acute, endogenous metabolic acidaemia speeds ø2 V'(E) kinetics in moderate exercise, consistent with carotid chemoreception contributing to the tightness of arterial pH-CO2 regulation and the magnitude of the transient arterial hypoxaemia.

Influence of cycling history on the ventilatory response to cycle-ergometry in humans: a role for respiratory memory?

The ventilatory (V' E) mechanisms subserving stability of alveolar and arterial PCO2 (PACO2, PaCO2) during moderate exercise (< lactate threshold, thetaL) remain controversial. As long-term modulation has been argued to be an important contributor to this control process, we proposed that subjects with no experience of cycling (NEx) might provide insight into this issue. With no exercise familiarization, 9 sedentary NEx subjects and 9 age-, sex-, and activity-matched controls (C) who had cycled regularly for recreational purposes since childhood completed a square-wave (6-min stage) cycle-ergometry test: 10 W-WR1-WR2-WR1-10 W; WR1 range 25-45 W, WR2 range 50-90 W. WRs were subsequently confirmed to

Noninvasive estimation of the lactate threshold in a subject with dissociated ventilatory and pulmonary gas exchange indices: a case report.

This case report describes the responses to incremental work-rate exercise in a healthy subject (with normal pulmonary function), for whom the pulmonary gas exchange (V-slope) and ventilatory-related indexes (ie, ventilatory equivalents and end-tidal partial pressures for O2 and CO2) uncharacteristically do not occur at the same metabolic rate. Based on the results of additional constant-work-rate exercise tests, we propose that in the (occasional) event of such a dissociation between the V-slope and ventilatory-related responses normally associated with the lactate threshold (theta L), then the V-slope index should take priority as the theta L estimator.

Spatial heterogeneity of quadriceps muscle deoxygenation kinetics during cycle exercise.

To test the hypothesis that, during exercise, substantial heterogeneity of muscle hemoglobin and myoglobin deoxygenation [deoxy(Hb + Mb)] dynamics exists and to determine whether such heterogeneity is associated with the speed of pulmonary O(2) uptake (pVo(2)) kinetics, we adapted multi-optical fibers near-infrared spectroscopy (NIRS) to characterize the spatial distribution of muscle deoxygenation kinetics at exercise onset. Seven subjects performed cycle exercise transitions from unloaded to moderate [GET) work rates and the relative changes in deoxy(Hb + Mb), at 10 sites in the quadriceps, were sampled by NIRS. At exercise onset, the time delays in muscle deoxy(Hb + Mb) were spatially inhomogeneous [intersite coefficient of variation (CV), 3~56% for GET]. The primary component kinetics (time constant) of muscle deoxy(Hb + Mb) reflecting increased O(2) extraction were also spatially inhomogeneous (intersite CV, 6~48% for GET) and faster (P < 0.05) than those of phase 2 pVo(2). However, the degree of dynamic intersite heterogeneity in muscle deoxygenation did not correlate significantly with phase 2 pVo(2) kinetics. In conclusion, the dynamics of quadriceps microvascular oxygenation demonstrates substantial spatial heterogeneity that must arise from disparities in the relative kinetics of Vo(2) and O(2) delivery increase across the regions sampled.

Control of breathing during cortical substitution of the spontaneous automatic respiratory rhythm.

This study addresses the following question: does the ventilatory control system adjust total ventilation in accord with the regulatory demands of the physiological dead space ventilation (VD) when the breathing frequency changes, and if so, how? A simple proportionality between the amplitude of the respiratory motor output (VT) and the respiratory period (TTOT) during such changes will not provide for regulation of arterial (PaCO2); the relationship requires a positive intercept of magnitude VD, i.e. VT=VATTOT+VD. We therefore determined the relationship between VT and TTOT when breathing frequency was changed in a ramp-like manner (from 6 to 20 cycles/min), in an imperceptible manner, during a paced-breathing protocol in which the subjects voluntarily triggered the breath onset, thereby imposing a rhythm different from the one spontaneously generated by the automatic central pattern generators (CPGs). While the resulting breath magnitude was strongly correlated to the breath duration (slope: 6.50+/-2.91 l/min) there was, in all cases, a statistically significant positive intercept on the VT axis (238+/-112 ml) leading to a relationship of the form: VT=VATTOT+VD. Consequently, the ventilatory output changed as a function of the breathing frequency-induced dead space ventilation changes, maintaining end-tidal PCO2 (PETCO2) constant. These results are consistent with a centrally set program for generating regulatory combinations of respiratory cycle durations and magnitudes that "take into account" the f-induced variation of dead space ventilation. This appears not to be dependent on the structures producing the respiratory rhythm (cortex versus central pattern generators). It is suggested that, during volitional control of breathing rhythm, the signal used for adjusting the magnitude to the timing of the ventilatory output is derived from information contained in the duration of preceding expiration.

Exercise training decreases ventilatory requirements and exercise-induced hyperinflation at submaximal intensities in patients with COPD.

STUDY OBJECTIVES: We hypothesized that endurance exercise training would reduce the degree of hyperinflation for a given level of exercise and thereby improve submaximal exercise endurance. METHODS: Twenty-four patients with COPD (mean FEV(1), 36.4 +/- 8.5% of predicted [+/- SD]) undertook a high-intensity cycle ergometer exercise training program for 45 min, three times a week for 7 weeks. Before and after training, the patients performed both an incremental exercise test to maximum and a constant work rate (CWR) test on a cycle ergometer at 75% of the peak work rate obtained in the pretraining incremental test. Ventilatory variables were measured breath-by-breath, and inspiratory capacity (IC) was measured every 2 min to assess changes in end-expiratory lung volume. RESULTS: After training, the increase in peak oxygen uptake was not statistically significant; however, the peak work rate increased by 12.9 +/- 10.3 W (p < 0.01). For the CWR test performed at the same work rate both before and after training, ventilation and breathing frequency (f) were lower after training (average, 1.97 L/min and 3.2 breaths/min, respectively; p < 0.01) and IC was greater (by an average of 133 mL, p < 0.05), signifying decreased hyperinflation. The increase in IC at the point of termination in the shortest CWR test for each individual (defined as isotime) correlated well with both the decreased f (r = 0.63, p = 0.001) and with the increase in CWR exercise endurance (average, 13.1 min, r = 0.46, p = 0.023). CONCLUSIONS: Exercise training in patients with severe COPD dramatically improves submaximal exercise endurance. Decreased dynamic hyperinflation may, in part, mediate the improvement in exercise endurance by delaying the attainment of a critically high inspiratory lung volume.

Pulmonary O2 uptake during exercise: conflating muscular and cardiovascular responses.

For moderate-intensity exercise (below lactate threshold, thetaL), muscle O(2) consumption (VO(2)) kinetics are expressed in a first-order phase 2 (or fundamental) pulmonary O(2) uptake (VO(2)) response: dVO(2)/dt . tau + DeltaVO(2)((t)) = DeltaVO(2)((ss)); where DeltaVO(2)(ss) is the steady-state VO(2) increment, and tau the VO(2) time constant (which is within approximately 10% of tauQVO(2)). A likely source of VO(2) control in this intensity domain is ADP-mediated, for which intramuscular phosphocreatine (PCr) may serve as a proxy variable. Whether, in reality, this behavior reflects the operation of a single homogeneous compartment is unclear, however; a multicompartment structure comprised of units having a similar DeltaVO(2)((ss)) but with widely varying tau can also yield a "well-fit" exponential response with an apparent single tau. In support of this is the inverse (although poorly predictive) correlation between tau and both theta(L) and VO(2max). Above theta(L), the fundamental VO(2) kinetics are supplemented with a delayed, slowly developing component that can set VO(2) on a trajectory towards VO(2max), and that has complex temporal- and intensity-related kinetics. This VO(2) slow component is also demonstrable in [PCr], suggesting that the decreased efficiency above theta(L) predominantly reflects a high phosphate cost of force production rather than a high O(2) cost of phosphate production. In addition, the oxygen deficit for the slow component is more likely to reflect a progressive shifting of DeltaVO(2)((ss)) rather than a single DeltaVO(2)((ss)) having a single tau.

Intensity-dependent tolerance to exercise after attaining V(O2) max in humans.

The tolerable duration of high-intensity, constant-load cycle ergometry is a hyperbolic function of power, with an asymptote termed critical power (CP) and a curvature constant (W') with units of work. It has been suggested that continued exercise after exhaustion may only be performed below CP, where predominantly aerobic energy transfer can occur and W' can be partially replenished. To test this hypothesis, six volunteers each performed cycle-ergometer exercise with breath-by-breath determination of ventilatory and pulmonary gas exchange variables. Initially, four exercise tests to exhaustion were made: 1). a ramp-incremental and 2). three high-intensity constant-load bouts at different work rates, to estimate lactate (theta(L)) and CP thresholds, W', and maximum oxygen uptake (Vo2 max). Subsequently, subjects cycled to the limit of tolerance (for approximately 360 s) on three occasions, each followed by a work rate reduction to 1). 110% CP, 2). 90% CP, and 3). 80% theta(L) for a 20-min target. W' averaged 20.9 +/- 2.35 kJ or 246 +/- 30 J/kg. After initial fatigue, 110% CP was tolerated for only 30 +/- 12 s. Each subject completed 20 min at 80% theta(L), but only two sustained 20 min at 90% CP; the remaining four subjects fatigued at 577 +/- 306 s, with oxygen consumption at 89 +/- 8% Vo2 max. The results support the suggestion that replenishing W' after fatigue necessitates a sub-CP work rate. The variation in subjects' responses during 90% CP was unexpected but consistent with mechanisms such as reduced CP consequent to prior high-intensity exercise, variation in lactate handling, and/or regional depletion of energy substrates, e.g., muscle glycogen.

The curvature constant parameter of the power-duration curve for varied-power exercise.

INTRODUCTION: The tolerable duration (t) for high-intensity cycle ergometry bears a hyperbolic relationship to the power output (P) with an asymptote termed the critical power (CP), and a curvature constant (W') that is numerically equivalent to an amount of work that can be performed above CP. The physiological nature of W' has received little consideration compared with CP, e.g., whether the total amount of work above CP remains constant when the power actually changes during the high-intensity task. PURPOSE: The purpose of this study was to compare W' derived from the standard estimation method, consisting of several different constant-P tests, and the total amount of work above CP during an exhausting exercise bout using a variable-P protocol. METHODS: Eleven healthy male subjects (age: 21-40 yr) volunteered to participate in this study. Each initially performed four-to-six high-intensity square-wave exercise bouts for estimation of CP [mean (SD); 213.3 (22.4) W] and W' [12.68 (3.08) kJ]. The subjects subsequently performed two variable-P tests to the limit of tolerance. During the first part, P was 117% or 134% of CP for a duration that expended approximately half of W'. The work rate was then abruptly increased to 134% (UP protocol) or decreased to 117% (DOWN protocol) of CP for the second part. RESULTS: There were no significant differences between W' [12.68 (3.08) kJ] and the total amount of work above CP during the UP [12.14 (4.18) kJ] and DOWN [12.72 (4.05) kJ] protocols (P > 0.05). CONCLUSION: We conclude that the work equivalent of W' is not affected by power variations during exhausting cycle ergometry, at least in the P range of 100-134% of CP.

A treadmill ramp protocol using simultaneous changes in speed and grade.

INTRODUCTION: A treadmill exercise test requiring a low initial metabolic rate that then increments the work rate linearly to reach the subject's limit of tolerance in approximately 10 min would have significant advantages for exercise testing and rehabilitation of subjects with impaired exercise tolerance. METHODS: We developed such a treadmill protocol that uses a linear increase in walking speed coupled with a curvilinear increase in treadmill grade to yield a linear increase in work rate. RESULTS: Twenty-two healthy, sedentary subjects performed both this new treadmill protocol and a standard cycle ergometry ramp protocol eliciting similar work rate profiles. The low initial treadmill speed and grade resulted in a low initial metabolic rate, commensurate with unloaded pedaling on a cycle ergometer (average [OV0312]O2 = 0.54 +/- 0.16 vs 46 +/- 0.12 l x min(-1)). This combination of simultaneous increase in speed and grade yielded a linear work rate and its oxygen uptake response (R2 = 0.96 +/- 0.03) with a slope of 11.4 +/- 2.4 ml x min(-1) x W(-1)-slightly, but significantly, higher than on the cycle (9.6 +/- 2.0 ml x min(-1) x W(-1)). This difference was attributed to unmeasured work associated, for example, with additional limb movements and frictional losses. As previously demonstrated, both the peak oxygen uptake and the estimated lactate threshold were higher on the treadmill than for cycle ergometry (averaging 23% and 27%, respectively, in these subjects). CONCLUSION: This treadmill protocol provides a linear profile of work rate as is currently standard for cycle ergometry and is appropriate for testing of subjects with low exercise tolerance.

Behavioral influences and physiological indices of ventilatory control in subjects with idiopathic hyperventilation.

Idiopathic hyperventilation has been defined as a respiratory-related psychophysiological complaint. This study attempted to clarify relationships between psychological and physiological variables in this condition. Participants demonstrated increased anxiety, depression, and symptoms consistent with hyperventilation. This was associated with a reduced peripheral chemosensitivity (isocapnic hypoxic rebreathe; -0.84 +/- 0.5 min-1.%O2(-1)), which was normalized with experimentally increased pCO2. Resting CO2 sensitivity was close to normal (2.1 +/- 1.0 min-1.mmHg-1). Breath hold time was significantly reduced versus controls (20.4 s +/- 12 s vs. 63 s +/- 31 s), and resting PETCO2 was correlated with the anxiety score. Also, the ventilatory response to moderate intensity exercise was augmented (vs. controls). The normalcy of pulmonary and chemoreceptor responses suggests that psychological factors may initiate this hyperventilation, which may become a conditioned response with an increased drive to breathe.

Muscle metabolism and activation heterogeneity by combined 31P chemical shift and T2 imaging, and pulmonary O2 uptake during incremental knee-extensor exercise.

The integration of skeletal muscle substrate depletion, metabolite accumulation, and fatigue during large muscle-mass exercise is not well understood. Measurement of intramuscular energy store degradation and metabolite accumulation is confounded by muscle heterogeneity. Therefore, to characterize regional metabolic distribution in the locomotor muscles, we combined 31P magnetic resonance spectroscopy, chemical shift imaging, and T2-weighted imaging with pulmonary oxygen uptake during bilateral knee-extension exercise to intolerance. Six men completed incremental tests for the following: (1) unlocalized 31P magnetic resonance spectroscopy; and (2) spatial determination of 31P metabolism and activation. The relationship of pulmonary oxygen uptake to whole quadriceps phosphocreatine concentration ([PCr]) was inversely linear, and three of four knee-extensor muscles showed activation as assessed by change in T2. The largest changes in [PCr], [inorganic phosphate] ([Pi]) and pH occurred in rectus femoris, but no voxel (72 cm3) showed complete PCr depletion at exercise cessation. The most metabolically active voxel reached 11 ± 9 mM [PCr] (resting, 29 ± 1 mM), 23 ± 11 mM [Pi] (resting, 7 ± 1 mM), and a pH of 6.64 ± 0.29 (resting, 7.08 ± 0.03). However, the distribution of 31P metabolites and pH varied widely between voxels, and the intervoxel coefficient of variation increased between rest (∼10%) and exercise intolerance (∼30-60%). Therefore, the limit of tolerance was attained with wide heterogeneity in substrate depletion and fatigue-related metabolite accumulation, with extreme metabolic perturbation isolated to only a small volume of active muscle (<5%). Regional intramuscular disturbances are thus likely an important requisite for exercise intolerance. How these signals integrate to limit muscle power production, while regional "recruitable muscle" energy stores are presumably still available, remains uncertain.

Pulmonary O2 uptake kinetics as a determinant of high-intensity exercise tolerance in humans.

Tolerance to high-intensity constant-power (P) exercise is well described by a hyperbola with two parameters: a curvature constant (W') and power asymptote termed "critical power" (CP). Since the ability to sustain exercise is closely related to the ability to meet the ATP demand in a steady state, we reasoned that pulmonary O(2) uptake (Vo(2)) kinetics would relate to the P-tolerable duration (t(lim)) parameters. We hypothesized that 1) the fundamental time constant (τVo(2)) would relate inversely to CP; and 2) the slow-component magnitude (ΔVo(2sc)) would relate directly to W'. Fourteen healthy men performed cycle ergometry protocols to the limit of tolerance: 1) an incremental ramp test; 2) a series of constant-P tests to determine Vo(2max), CP, and W'; and 3) repeated constant-P tests (WR(6)) normalized to a 6 min t(lim) for τVo(2) and ΔVo(2sc) estimation. The WR(6) t(lim) averaged 365 ± 16 s, and Vo(2max) (4.18 ± 0.49 l/min) was achieved in every case. CP (range: 171-294 W) was inversely correlated with τVo(2) (18-38 s; R(2) = 0.90), and W' (12.8-29.9 kJ) was directly correlated with ΔVo(2sc) (0.42-0.96 l/min; R(2) = 0.76). These findings support the notions that 1) rapid Vo(2) adaptation at exercise onset allows a steady state to be achieved at higher work rates compared with when Vo(2) kinetics are slower; and 2) exercise exceeding this limit initiates a "fatigue cascade" linking W' to a progressive increase in the O(2) cost of power production (Vo(2sc)), which, if continued, results in attainment of Vo(2max) and exercise intolerance. Collectively, these data implicate Vo(2) kinetics as a key determinant of high-intensity exercise tolerance in humans.

The role of nitrogen oxides in human adaptation to hypoxia.

Lowland residents adapt to the reduced oxygen availability at high altitude through a process known as acclimatisation, but the molecular changes underpinning these functional alterations are not well understood. Using an integrated biochemical/whole-body physiology approach we here show that plasma biomarkers of NO production (nitrite, nitrate) and activity (cGMP) are elevated on acclimatisation to high altitude while S-nitrosothiols are initially consumed, suggesting multiple nitrogen oxides contribute to improve hypoxia tolerance by enhancing NO availability. Unexpectedly, oxygen cost of exercise and mechanical efficiency remain unchanged with ascent while microvascular blood flow correlates inversely with nitrite. Our results suggest that NO is an integral part of the human physiological response to hypoxia. These findings may be of relevance not only to healthy subjects exposed to high altitude but also to patients in whom oxygen availability is limited through disease affecting the heart, lung or vasculature, and to the field of developmental biology.