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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 combined31P 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) unlocalized31P magnetic resonance spectroscopy; and 2) spatial determination of31P 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 of31P 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 (

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 O2 uptake (V̇o2) kinetics would relate to the P-tolerable duration (tlim) parameters. We hypothesized that 1) the fundamental time constant (τV̇o2) would relate inversely to CP; and 2) the slow-component magnitude (ΔV̇o2sc) 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 V̇o2max, CP, and W′; and 3) repeated constant-P tests (WR6) normalized to a 6 min tlim for τV̇o2 and ΔV̇o2sc estimation. The WR6 tlim averaged 365 ± 16 s, and V̇o2max (4.18 ± 0.49 l/min) was achieved in every case. CP (range: 171–294 W) was inversely correlated with τV̇o2 (18–38 s; R2 = 0.90), and W′ (12.8–29.9 kJ) was directly correlated with ΔV̇o2sc (0.42–0.96 l/min; R2 = 0.76). These findings support the notions that 1) rapid V̇o2 adaptation at exercise onset allows a steady state to be achieved at higher work rates compared with when V̇o2 kinetics are slower; and 2) exercise exceeding this limit initiates a “fatigue cascade” linking W′ to a progressive increase in the O2 cost of power production (V̇o2sc), which, if continued, results in attainment of V̇o2max and exercise intolerance. Collectively, these data implicate V̇o2 kinetics as a key determinant of high-intensity exercise tolerance in humans.

The purpose was to study the effect of endoscopic thoracic sympathectomy (ETS) for palmar and/or axillary hyperhidrosis on physiological responses at rest, and during sub-maximal and maximal exercise in ten healthy patients (7 females and 3 males 18-40 years old) with idiopathic palmar and/or axillary hyperhidrosis. T2-T3 thoracoscopic sympathectomy was performed using a simplified one stage bilateral procedure. Physiological variables were recorded at rest and during sub-maximal (steady-state) and maximal treadmill exercise immediately prior to and 70 days (+/-7.5, SD) after bilateral ETS. Exercise performance capacity and peak VO(2) were not found to be different following bilateral ETS than prior to the ETS. However, heart rate was significantly reduced at rest (14%), at sub-maximal exercise (12.3%), and at peak exercise (5.7%), together with a significant increase in oxygen pulse (11.8, 12.7, and 7.8%, respectively). The rate pressure product (RPP) was also significantly reduced following the surgical procedure at all three study stages, while all other physiological variables measured remained unchanged. It is suggested that thoracic-sympathetic denervation affects the heart, sweating, and circulation of the respective denervated region but does not affect exercise performance or mechanical/physiologic efficiency, despite a significant reduction in heart rate (both at rest and during exercise). The latter was, most likely, fully compensated by an increase in stroke volume and less likely by an improved muscle O(2) extraction due to more efficient blood distribution, keeping the work-rate and oxygen uptake unaffected.

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 O 2 and CO 2 ) 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 (θL), then the V-slope index should take priority as the θL estimator.

A recent bout of high-intensity exercise can alter the balance of aerobic and anaerobic energy provision during subsequent exercise above the lactate threshold (θL). However, it remains uncertain whether such “priming” influences the tolerable duration of subsequent exercise through changes in the parameters of aerobic function [e.g., θL, maximum oxygen uptake (V̇o2max)] and/or the hyperbolic power-duration (P-t) relationship [critical power (CP) and the curvature constant (W′)]. We therefore studied six men performing cycle ergometry to the limit of tolerance; gas exchange was measured breath-by-breath and arterialized capillary blood [lactate] was measured at designated intervals. On different days, each subject completed 1) an incremental test (15 W/min) for estimation of θL and measurement of the functional gain (ΔV̇o2/ΔWR) and V̇o2peak and 2) four constant-load tests at different work rates (WR) for estimation of CP, W′, and V̇o2max. All tests were subsequently repeated with a preceding 6-min supra-CP priming bout and an intervening 2-min 20-W recovery. The hyperbolicity of the P-t relationship was retained postpriming, with no significant difference in CP (241 ± 39 vs. 242 ± 36 W, post- vs. prepriming), V̇o2max (3.97 ± 0.34 vs. 3.93 ± 0.38 l/min), ΔV̇o2/ΔWR (10.7 ± 0.3 vs. 11.1 ± 0.4 ml·min−1·W−1), or the fundamental V̇o2 time constant (25.6 ± 3.5 vs. 28.3 ± 5.4 s). W′ (10.61 ± 2.07 vs. 16.13 ± 2.33 kJ) and the tolerable duration of supra-CP exercise (−33 ± 11%) were each significantly reduced, despite a less-prominent V̇o2 slow component. These results suggest that, following supra-CP priming, there is either a reduced depletable energy resource or a residual fatigue-metabolite level that leads to the tolerable limit before this resource is fully depleted.

Resumo: A elaboração deste documento pelo grupo de trabalho da European Respiratory Society tem como objectivo apresentar as recomendações sobre o uso clínico dos testes de exercício em doentes com patologia cardiorrespiratória, dando particular ênfase à avaliação funcional, à avaliação do prognóstico e à avaliação das intervenções terapêuticas.A intolerância ao esforço físico é um dos sintomas mais frequentes, condicionando a perda de qualidade de vida do doente com patologia cardiorrespiratória crónica. Pode definir-se âintolerância ao exercícioâ numa perspectiva clínica à incapacidade que o doente apresenta para realizar tarefas que os indivíduos saudáveis considerariam toleráveis.A intolerância ao exercício, considerada em termos do pico de consumo de oxigénio atingido no esforço máximo (VâO2pico) não pode ser prevista por parâmetros avaliados em repouso, como o volume expiratório máximo no primeiro segundo (FEV1), a transferência alvéolo-capilar do monóxido de carbono (DLCO), a fracção de ejecção do ventrículo esquerdo ou o índice de massa corporal (IMC). A avaliação em exercício impõe alguns desafios técnicos: a aplicação de protocolos específicos de incremento de carga de forma precisa e reprodutível, com o recurso habitual a ergómetros, tais como a bicicleta ergométrica e o tapete rolante.A prova de exercício cardiorrespiratória (CPET) é considerada o gold standard na avaliação das causas de intolerância ao exercício em doentes com doença cardíaca e pulmonar e é baseado no princípio de que a falência do sistema ocorre tipicamente quando o sistema (seja ele músculo-energético, cardiovascular ou pulmonar) se encontra sob stress. A CPET compreende a imposição de um exercício com cargas crescentes (ou seja, incremental) limitado por sintomas, enquanto se monitorizam as variáveis cardiopulmonares (exemplo: consumo de oxigénio (VâO2), produção de dióxido de carbono (VâCO2), ventilação minuto (VâE), frequência cardíaca (fC)), a percepção de sintomas (exemplo: a dispneia e o desconforto nos membros inferiores) e, quando necessárias, as avaliações da dessaturação arterial do oxigénio relacionada com o esforço, da hiperinsuflação dinâmica e da força muscular dos membros. Os sistemas são forçados até ao seu limite tolerável, de forma controlada, o que permite detectar respostas que identificam padrões de alteração e que podem ser relacionadas com padrões de referência previamente estudados e publicados pelas sociedades respiratórias europeia e americanas1-3.Neste documento, é descrito o papel da CPET como auxiliar no diagnóstico e na avaliação funcional e prognóstica. A CPET pode: â Fornecer uma medição objectiva da capacidade para o exercício; â Identificar os mecanismos que limitam a tolerância ao exercício; â Estabelecer índices de prognóstico; â Monitorizar a progressão da doença e a resposta à s intervenções terapêuticas. â Auxiliar no diagnóstico, em situações de broncoconstrição induzida pelo exercício e de dessaturação arterial do oxigénio. Na identificação das causas de intolerância ao exercício, a CPET pode detectar: â Alterações na entrega de oxigénio (desde a sua entrada nas vias aéreas, passando pelo sistema de transporte cardiocirculatório, até à entrega à s mitocôndrias das fibras musculares); â Limitação ventilatória no exercício; â Alteração do controlo ventilatório; â Alteração das trocas gasosas pulmonares; â Percepção excessiva de sintomas (exemplos: dispneia, precordialgia, fadiga muscular periférica); â Disfunção metabólica muscular; â Descondicionamento; â Fraco esforço dispendido. Com um bom esforço realizado, se o valor do pico do consumo de oxigénio atingido foi normal e o motivo para parar a prova foi dispneia ou fadiga muscular, então pode considerar-se que o indivíduo estudado tem uma normal tolerância ao exercício. Este cenário irá excluir doença pulmonar (DPOC, doença intersticial pulmonar, doença vascular pulmonar) ou cardíaca (insuficiência cardíaca congestiva) significativas como causa de intolerância.A prova de exercício cardiopulmonar pode auxiliar no diagnóstico diferencial entre limitação no esforço de origem pulmonar ou cardiocirculatória. Pode fornecer um perfil de respostas que caracterizam determinadas doenças; exemplo: na DPOC são frequentes a limitação ventilatória, a hiperinsuflação dinâmica, a dessaturação arterial com o exercício, a dispneia, a disfunção dos músculos periféricos; na doença intersticial pulmonar são frequentes a dispneia, a restrição ventilatória mecânica e as alterações graves das trocas gasosas. Outros padrões de respostas podem ser encontrados na broncoconstrição induzida pelo exercício, na doença vascular pulmonar, na insuficiência cardíaca e em cardiopatias congénitas. A avaliação cardiorrespiratória no exercício fornece ainda indicadores prognósticos em várias doenças. Descrevem-se neste documento vários trabalhos que estudaram os parâmetros indicadores de prognóstico em doenças como a DPOC, a doença intersticial pulmonar, a hipertensão pulmonar primária, a fibrose quística e a insuficiência cardíaca.Este documento demonstra ainda a utilidade dos testes de exercício na definição das respostas à s intervenções terapêuticas, em avaliações seriadas.O grupo de trabalho envolvido neste documento considerou importante apresentar as indicações baseadas na evidência para a realização dos testes de exercício na prática clínica. A evidência actual é clara quanto à utilidade da prova de exercício cardiopulmonar, das provas de marcha e das provas de carga constante na avaliação do grau de intolerância ao exercício, do prognóstico e dos efeitos das intervenções terapêuticas em doentes adultos com doença pulmonar crónica (DPOC, doença intersticial pulmonar, hipertensão pulmonar primária), em crianças e adultos com fibrose quística, em crianças e adultos com broncospasmo induzido pelo exercício, em adultos com insuficiência cardíaca congestiva e em crianças e adolescentes com cardiopatias congénitas.Na elaboração deste documento, os autores pretenderam fornecer as respostas à s perguntas que se colocam com frequência na prática clínica: â Quando se deve pedir uma avaliação da intolerância ao esforço? â Qual o teste mais adequado? â Quais as variáveis a seleccionar na avaliação do prognóstico de determinada doença ou na avaliação do efeito de uma intervenção terapêutica particular? O documento contém ainda um suplemento que pode ser obtido on-line e que descreve as bases fisiológicas subjacentes aos parâmetros avaliados nas provas de exercício cardiopulmonar.

During moderate exercise (below the lactate threshold, (thetaL)), muscle CO(2) production ( Q(CO2)) kinetics are monoexponential, with a time constant (tau) similar to that of O(2) consumption. Following a delay incorporating the muscle-lung vascular transit time, Q(CO2) is expressed at the lungs (V(CO2)) with an appreciably longer tau, reflecting the influence of intervening high-capacitance CO(2) stores. Above (thetaL), kinetics become complex, resulting from the conflation of the differing rates of HCO(3)(-) breakdown and degrees of compensatory hyperventilation with that of the underlying aerobic component. During incremental exercise, the increased rate of relative to pulmonary O(2) uptake (V(CO2)) can be used to quantify (thetaL) validly if aerobic and hyperventilatory sources can be ruled out, i.e. (thetaL) is then attributable to the decrease in muscle and blood [HCO(3)(-)]. In many cases, however, very rapid incrementation of work rate and/or prior depletion of CO(2) stores (by volitional or anticipatory hyperventilation) can yield a 'false positive' non-invasive estimation of (thetaL) ('pseudo-threshold') resulting from a slowing of the rate of wash-in of transient CO(2) stores.

The O2uptake (V̇o2) response to ramp incremental (RI) exercise does not consistently demonstrate plateau-like behavior at the limit of tolerance, and hence the requirements for a maximum V̇o2commonly are not met, despite apparent maximum effort. We sought to determine whether an appended step exercise (SE) test at a work rate greater than that achieved in a preceding ramp test would establish the plateau criterion. Seven healthy male adults performed RI cycle ergometry (20 W/min) to the limit of tolerance, followed by 5-min recovery (20 W) and then an SE test at 105% (RISE-105) of the final work rate (WRpeak) achieved during RI. Five of these subjects also performed an RI test followed by SE at 95% WRpeak(RISE-95). V̇o2was measured breath by breath using a turbine and mass spectrometer. The average of the final 15 s of RI or SE was used to establish respective V̇o2peaks. When V̇o2peak was approached, a constant V̇o2value (e.g., a plateau) was not discernable during any RI or SE component of the tests. Although the WRpeak[mean (SD)] was higher during the SE portion [359 W (SD 31)] than during the RI portion [341 W (SD 29)] of the RISE-105, the peak V̇o2was not different [SE, 4.30 l/min (SD 0.51); RI, 4.33 l/min (SD 0.52); P = 0.49; n = 7]. Similarly, in the RISE-95 test, WRpeakwas 310 W (SD 31) for the SE portion and 326 W (SD 32) for the RI portion, yet the peak V̇o2values were not different [SE, 4.12 l/min (SD 0.53); RI, 4.11 l/min (SD 0.48); P = 0.78; n = 5]. The lack of notable difference between the V̇o2peaks established at different WRpeakvalues in our RISE protocols provides the plateau criterion for verification of maximum V̇o2in a single test session, even when the data response profiles do not themselves evidence a plateau.

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.

Objective. To investigate muscle energetics in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and measure serum cortisol, prolactin and CD4 + /CD8 + T-cell levels during and after controlled exhaustive exercise. Methods. Patients with RA (n=7), patients with SLE (n=6) and healthy individuals (HI) (n=10) performed incremental cycle ergometry to the limit of tolerance. Ventilation, oxygen uptake (VO 2 ) and carbon dioxide output were measured and the lactate threshold (LT) was estimated. Serum cortisol, prolactin, CD4 + and CD8 + lymphocyte subset levels were determined at baseline, peak exercise and 1 h after exercise. Results. Exercise tolerance was reduced in patients with RA and patients with SLE, as reflected by peak VO 2 and LT, but muscle energetics were not altered. In RA and SLE, there was significant reduction in cortisol levels at peak (-10%; P = 0.03) and post-exercise times (-36%; P = 0.05). Prolactin varied significantly at peak exercise in HI only (+60%; P = 0.05). There was a significant reduction in CD4 + T cells at peak exercise in RA (-15%; P=0.02) and SLE patients (-8%; P=0.04) and an increase after exercise in SLE patients (+11%; P=0.03). In HI, CD8 + T cells increased significantly (+47%; P=0.01) at peak exercise, but this was not found in RA and SLE patients. A significant reduction in CD8 + T cells was noted after exercise in SLE patients (-6%; P=0.05). Conclusion. RA and lupus patients do not have significantly altered muscle energetics, but have abnormal cortisol, prolactin and CD4 + /CD8 4 T-cell responses to exercise. Further studies need to be carried out to evaluate whether short bouts of strenuous exercise have detrimental clinical effects.

1. A prior bout of high-intensity square-wave exercise can increase the temporal adaptation of pulmonary oxygen uptake (.V(O2)) to a subsequent bout of high-intensity exercise. The mechanisms controlling this adaptation, however, are poorly understood. 2. We therefore determined the dynamics of intramuscular [phosphocreatine] ([PCr]) simultaneously with those of .V(O2) in seven males who performed two consecutive bouts of high-intensity square-wave, knee-extensor exercise in the prone position for 6 min with a 6 min rest interval. A magnetic resonance spectroscopy (MRS) transmit-receive surface coil under the quadriceps muscle allowed estimation of [PCr]; .V(O2) was measured breath-by-breath using a custom-designed turbine and a mass spectrometer system. 3. The .V(O2) kinetics of the second exercise bout were altered compared with the first such that (a) not only was the instantaneous rate of .V(O2) change (at a given level of .V(O2)) greater but the phase II tau was also reduced - averaging 46.6 +/- 6.0 s (bout 1) and 40.7 +/- 8.4 s (bout 2) (mean +/- S.D.) and (b) the magnitude of the later slow component was reduced. 4. This was associated with a reduction of, on average, 16.1% in the total exercise-induced [PCr] decrement over the 6 min of the exercise, of which 4.0% was due to a reduction in the slow component of [PCr]. There was no discernable alteration in the initial rate of [PCr] change. The prior exercise, therefore, changed the multi-compartment behaviour towards that of functionally first-order dynamics. 5. These observations demonstrate that the .V(O2) responses relative to the work rate input for high-intensity exercise are non-linear, as are, it appears, the putative phosphate-linked controllers for which [PCr] serves as a surrogate.

To characterize the determinants of the power-duration (W-t) relationship in patients with chronic obstructive pulmonary disease (COPD), we evaluated 8 nonhypoxemic patients (FEV(1) = 1.27 +/- 0.26 L) and 10 healthy controls. After an initial maximum-incremental exercise test on cycle ergometer (peak), the subjects underwent four high-intensity constant-load tests to the limit of tolerance (t), each on different days. The W-t relationship was found to be hyperbolic in both groups. Absolute values of both the critical power asymptote (theta(F)) and the curvature constant (W') were lower in patients than in control subjects. However, when expressed as percentage of peak work rate theta(F) was significantly higher in patients compared with control subjects (81.8 +/- 3.3% versus 67.5 +/- 3.7%, respectively, p0.01). There were severe reductions in t in the patients that were consistently associated with higher breathlessness scores and V E/MVV ratios. Interestingly, all patients were able to sustain exercise at theta(F) for 20 min despite near-maximum physiological and subjective stresses. We conclude that the reductions of both parameters of the hyperbolic W-t relationship (theta(F) and W') in patients with COPD were due to the ventilatory constraints and their sensory consequences. Importantly, theta(F) separated a "sustainable" from a "nonsustainable" exercise-intensity domain: this parameter consistently occurred closer to peak work rate in patients than the healthy control subjects.

In order to evaluate the determinants of the metabolic cost for cycle ergometry, we analyzed the relationship between VO 2 and leg mass (LM) and total body mass (TBM) in 71 randomly-selected sedentary subjects (34 men), aged 20 to 80. Participants performed constant work rate (WR) tests at 0, 25, and 50 W (at 60 rpm) for 6 minutes in a randomized sequence: gross VO 2 , gross efficiency, and work efficiency were related to TBM and LM as assessed by dual energy x-ray absorptiometry. We found that gross VO 2 and gross efficiency were more strongly related to LM than TBM but work efficiency values were independent of both (P > 0.05). Significantly higher values of VO 2 /TBM were found in subjects with large LM/TBM ratios and vice-versa; VO 2 /LM, however, did not change with anthropometric characteristics. Gross VO 2 (mL/min) was predicted by a LM-based equation (10.6 [WR, W] + 16.8 [LM, kg] + 75) with a mean error below 5%: this equation predicted the cost more accurately than previous TBM-based formulations (P < 0.01). We conclude that leg mass actually provides the preferred frame of reference for predicting the oxygen cost for cycle ergometry at 60 rpm in sedentary subjects, independent of age or gender.

Our understanding of O2 uptake (V˙o 2) control mechanisms during exercise may be improved by the simultaneous determination of the kinetics of intramuscular high-energy phosphate turnover and pulmonary V˙o 2. We therefore developed a technique for remote gas-exchange analysis while subjects exercised in a whole body 1.5-T NMR system. Knee-extension exercise was performed against restraining rubber bands in the prone position. Free induction decays were acquired every 1,875 ms by using a transmit-receive coil, which was placed under the quadriceps. This allowed 31P spectra of intramuscular ATP, Pi, and creatine phosphate dynamics to be determined every 15 s. Airflow was measured with a custom-designed turbine and a 45-ft.-long cable to reach the volume-measuring module. This was located in an adjacent radio-frequency-shielded room, as was the respiratory mass spectrometer, which also used a 45-ft.-long sampling line. The respired gas profiles were not discernibly different from those that used the standard inlet; the increase in the delay was readily incorporated into the breathby-breath algorithm, allowing theV˙o 2 kinetics to be determined in concert with those of intramuscular phosphate metabolism.

This study assessed blood flow in the common femoral, superficial femoral and profunda femoris arteries, the effects of vasodilator metabolites and changes in blood pressure and pulse during recovery after high intensity exercise (Wingate test). Mean common femoral artery flow increased sevenfold in response to the exercise. The subsequent decline in mean common femoral artery flow was mono-exponential with a mean time constant of 19 min. The post-exercise increase in profunda femoris artery flow (ninefold) was significantly greater than the superficial femoral artery flow (fourfold, P < 0.05). Systolic blood pressure and heart rate decreased monotonically throughout recovery. In contrast, diastolic blood pressure showed a significant fall below baseline at 3 min (P < 0.05) with a return to baseline at 60 min. The greatest drop below baseline (approximately 20 mmHg) occurred around 7 min. Lactate reached a maximum of 13.6 +/- 2.3 mmol -1 at 8 min (P < 0.05) and was still significantly above baseline at 60 min. pH remained below 7.2 until 20 min of recovery. The results demonstrate that following high intensity exercise, blood flow to the limbs appears to be controlled by complex interactions of various vaso-active metabolites, each contributing proportionally more at different times during recovery.

We tested the hypothesis that infused epinephrine (Epi) would augment the slow phase of oxygen uptake (VO2) during heavy exercise. Six normal healthy males initially performed a ramp test on a cycle ergometer to estimate the lactate threshold (LT) and determine peak VO2. Each subject then performed two 20-min constant-load tests at a power output calculated to elicit a VO2 equal to estimated LT + 0.2(peak VO2--estimated LT) under control conditions throughout and with an intravenous infusion of Epi from minutes 10 to 20 at a rate of 100 ng.kg-1.min-1. Pulmonary gas exchange variables were determined breath by breath. Arterialized venous blood was repeatedly sampled from the dorsum of the heated hand. Epi infusion elevated (P < 0.05) plasma Epi concentration (i.e., from 420 +/- 130 pg/ml at minute 10 to 2,190 +/- 410 pg/ml at minute 20) but had no effect on plasma norepinephrine or K+ concentrations. Concentrations of blood lactate and pyruvate were increased, pH was decreased, and base excess became more negative by infusion of Epi (P < 0.05). Epi infusion increased (P < 0.05) CO2 production and the respiratory exchange ratio but had no effect on ventilation or VO2. VO2 increased (P < 0.05) to the same extent in both control (3.14 +/- 0.12 l/min at minute 10, 3.28 +/- 0.12 l/min at minute 20) and Epi infusion (3.10 +/- 0.11 l/min at minute 10, 3.25 +/- 0.11 l/min at minute 20) trials. We therefore concluded that neither Epi nor its associated humoral consequences contribute significantly to the slow phase of VO2 kinetics during heavy exercise.

During incremental work rate exercise, ventilation (V E ) typically increases in proportion to the metabolic rate until the onset of a progressive metabolic acidemia induces an additional compensatory hyperpnea. We examined the control characteristics of this compensatory mechanism in seven healthy subjects performing incremental cycle ergometry to their limit of tolerance at different levels of lower-body positive pressure (LBPP) at 0, 15, 30, and 45 Torr in order to determine if LBPP could alter the occurrence of the ventilatory threshold. Ventilatory responses and pulmonary gas exchange variables were measured breath-by-breath while ‘arterialized’-venous blood was sampled from the dorsum of the heated hand for determination of [lactate], pH, and [K + ]. The ventilatory threshold was progressively reduced with increasing levels of LBPP: Ventilatory threshold = 2.33 − (0.0173 · LBPP ); ( r 2 = 0.59, P E /V O 2 ) and carbon dioxide (V E /V CO 2 ) were systematically elevated at work rates above 50 W by increases in respiratory frequency which also resulted in lower Pet CO 2 and higher Pet O 2 values. As [lactate] was only slightly elevated above control (dGlactate −1 ) while pH and [K + ] were unchanged, it seems unlikely that the LBPP-induced hyperpnea can be attributed to activation of peripheral arterial or central chemoreceptors. These findings suggests a ventilatory stimulus may be generated by an LBPP-induced reduction in perfusion with the subsequent accumulation of intramuscular metabolites at the working limb and/or a direct effect of increased intramuscular tissue pressure.

The physiological equivalents of the curvature constant (W′) of the high-intensity power-duration (P-tLIM) relationship are poorly understood, although they are presumed to reach maxima/minima at exhaustion. In an attempt to improve our understanding of the determinants of W′, we therefore aimed to determine its recovery kinetics following exhaustive exercise (which depletes W′) concomitantly with those of O2 uptake (V̇o2, a proxy for the kinetics of phosphocreatine replenishment) and blood lactate concentration ([L−]). Six men performed cycle-ergometer exercise to tLIM: a ramp and four constant-load tests, at different work rates, for estimation of lactate threshold, W′, critical power (CP), and maximum V̇o2. Three further exhausting tests were performed at different work rates, each preceded by an exhausting “conditioning” bout, with intervening recoveries of 2, 6, and 15 min. Neither prior exhaustion nor recovery duration altered V̇o2 or [L−] at tLIM. Postconditioning, the P-tLIM relationship remained well characterized by a hyperbola, with CP unchanged. However, W′ recovered to 37 ± 5, 65 ± 6, and 86 ± 4% of control following 2, 6, and 15 min of intervening recovery, respectively. The W′ recovery was curvilinear [interpolated half time ( t1/2) = 234 ± 32 s] and appreciably slower than V̇o2 recovery ( t1/2 = 74 ± 2 s) but faster than [L−] recovery ( t1/2 = 1,366 ± 799 s). This suggests that W′ determines supra-CP exercise tolerance, its restitution kinetics are not a unique function of phosphocreatine concentration or arterial [L−], and it is unlikely to simply reflect a finite energy store that becomes depleted at tLIM.

Among the benefits expected to result from a therapeutic intervention in patients with impaired systemic functioning is an increase in exercise tolerance. For this a constant high-intensity work rate has been shown to provide a more sensitive index of improvement than the maximum work rate, or oxygen uptake, on a symptom-limited incremental test. However, the extremely large variability of the improvement in this particular index of tolerance undermines the ability to make general inferences for the underlying functional improvement. We argue that this is a necessary consequence of the particular work rate chosen for the test and the change in the parameters of the subject's hyperbolic power-duration relationship for that form of exercise: its "critical power" and "curvature constant". Without knowledge of these features, any absolute or per cent increase in tolerance time to a single constant-load exercise bout must be interpreted with caution regarding the physiological benefit(s) that have accrued from the intervention.

To determine the role of cardiac reflexes in mediating exercise hyperpnea, we investigated ventilatory responses to treadmill exercise in seven calves with artificial hearts and seven controls. In both groups, the ventilatory responses were adequate for the metabolic demands of the exercise; this resulted in regulation of arterial PCO2 and pH despite the absence of cardiac output increase in the implanted group. In this group, there was a small but significant reduction of arterial PO2 by 4 +/- 3 Torr and a rise of blood lactate by 1.1 +/- 1 mmol/l. When cardiac output was experimentally increased in the implanted calves to a level commensurate with that spontaneously occurring in the control calves, ventilation was not affected. However, experimental reductions of cardiac output led to an immediate augmentation of exercise hyperpnea by 4.56 +/- 4.3 l/min and a further significant lactate increase of 1.2 +/- 1.22 mmol/l that was associated with a significant decrease in the exercise O2 consumption (0.32 +/- 0.13 l/min). These observations indicate that neither cardiac nor hemodynamic effects of increased cardiac output constitute an obligatory cause of exercise hyperpnea in the calf.

The effect of cardiovascular adjustments on the coupling of cellular to pulmonary gas exchange during unsteady states of exercise remains controversial. Computer simulations were performed to assess these influences on O2 delivery and pulmonary O2 uptake (pVO2). Algorithms were developed representing muscle and “rest-of-body” compartments, connected in parallel by arterial and venous circulations to a pump-and-lungs compartment. Exercise-induced increases in VO2 and cardiac output went to the muscle compartment. Model parameters [e.g., time constants for blood flow and muscle O2 uptake (mVO2)] could be varied independently. Simulation results demonstrated that 1) the rise in pVO2 during exercise contains three phases; 2) the contribution of changes in venous O2 stores to pVO2 kinetics and the O2 deficit occur almost entirely in phase 1; 3) under a wide variety of manipulations, the kinetics of pVO2 in phase 2 were within a couple of seconds of that assigned to mVO2 (i.e., there is not an obligatory slowing of VO2 kinetics at the lungs relative to those at the muscles; 4) by use of available estimates of blood flow adjustment, O2 delivery would not limit mVO2 after exercise onset; and 5) blood flow could limit O2 delivery in recovery, if blood flow returned to base-line levels at rates similar to those during the on-transient phase.

The dynamics of pulmonary O2uptake (V˙o2) during the on-transient of high-intensity exercise depart from monoexponentiality as a result of a “slow component” whose mechanisms remain conjectural. Progressive recruitment of glycolytic muscle fibers, with slow O2utilization kinetics and low efficiency, has, however, been suggested as a mechanism. The demonstration of high- and low-pH components of the exercising skeletal muscle31P magnetic resonance (MR) spectrum [inorganic phosphate (Pi) peak] at high work rates (thought to be reflective of differences between oxidative and glycolytic muscle fibers) is also consistent with this conjecture. We therefore investigated the dynamics ofV˙o2(using a turbine and mass spectrometry) and intramuscular ATP, phosphocreatine (PCr), and Piconcentrations and pH, estimated from the31P MR spectrum. Eleven healthy men performed prone square-wave high-intensity knee extensor exercise in the bore of a whole body MR spectrometer. A V˙o2slow component of magnitude 15.9 ± 6.9% of the phase II amplitude was accompanied by a similar response (11.9 ± 7.1%) in PCr concentration. Only five subjects demonstrated a discernable splitting of the Pipeak, however, which began from between 35 and 235 s after exercise onset and continued until cessation. As such, the dynamics of the pH distribution in intramuscular compartments did not consistently reflect the temporal features of theV˙o2slow component, suggesting that Pisplitting does not uniquely reflect the activity of oxidative or glycolytic muscle fibers per se.

In order to evaluate the determinants of the metabolic cost for cycle ergometry, we analyzed the relationship between VO2 and leg mass (LM) and total body mass (TBM) in 71 randomly-selected sedentary subjects (34 men), aged 20 to 80. Participants performed constant work rate (WR) tests at 0, 25, and 50 W (at 60 rpm) for 6 minutes in a randomized sequence: gross VO2, gross efficiency, and work efficiency were related to TBM and LM as assessed by dual energy x-ray absorptiometry. We found that gross VO2 and gross efficiency were more strongly related to LM than TBM but work efficiency values were independent of both (P0.05). Significantly higher values of VO2TBM were found in subjects with large LM/TBM ratios and vice-versa; VO2/LM, however, did not change with anthropometric characteristics. Gross VO2 (mL/min) was predicted by a LM-based equation (10.6 [WR, W] + 16.8 [LM, kg] +75) with a mean error below 5%: this equation predicted the cost more accurately than previous TBM-based formulations (P0.01). We conclude that leg mass actually provides the preferred frame of reference for predicting the oxygen cost for cycle ergometry at 60 rpm in sedentary subjects, independent of age or gender.

The oxygen uptake response to moderate-intensity exercise (i.e.anaerobic threshold (an)) has been characterised with a gain (i.e. response amplitude per increment of work rate) and time constant that do not vary appreciably at different work rates or between the on- and off-transients. Above an, the response becomes more complex with an early component that typically projects to a value that has a gain similar to that of thean response, but which is supplemented by the addition of a delayed slow kinetic component. We therefore established a constant target VO2 (VO21) for each subject such that with different imposed work rates the contribution to VO21 from the slow phase varied over a wide range. Work rates were chosen so that VO21 was attained at 2-24 min. Five subjects (aged 21-58 years) cycled at four to five different work rates. VO2 was measured breath-by-breath, at VO21 the work rate was abruptly reduced and the subject recovered by cycling unloaded for 15 min. Unlike the on-transient, for which the slow component shows a long delay, the off-transient was best fitted as two simultaneous exponential components. The slower off-transient component had a small amplitude and long time constant, but did not differ significantly among the various tests. The off-transient kinetics for VO2 therefore was independent of the magnitude of the contribution to the slow phase from the on-transient kinetics.

The effect of 4 weeks' treatment with oral-L-carnitine (100 mg/kg per day) on carnitine status and metabolic parameters during an incremental ramp exercise test in a 12-year-old girl with isovaleric acidaemia was examined to determine its possible therapeutic role. The maximum work rate achieved increased from 110 to 120 watts; oxygen consumption at anaerobic threshold from 600 to 800 L/min; peak oxygen consumption from 1270 to 1450 L/min; and oxygen pulse, a measure of cardiac output, from 7.0 to 8.1 L/beat. These changes were associated with increases in plasma and urinary free and acyl carnitine concentrations but no change in physical activity. This observed effect of L-carnitine on exercise performance may be on cardiac or skeletal muscle function or both. We conclude that, in this single patient with isovaleric acid-aemia, L-carnitine supplementation had objective benefits and further studies on more patients are warranted.

The effects of prior exercise on O2 uptake (VO2) kinetics during supra-lactate threshold (LT) cycling were assessed in 11 subjects. Protocols consisted of two consecutive 6-min work bouts separated by 0 W (6 min) with 1) both bouts sub-LT, 2) both bouts supra-LT, 3) bout 1 sub-LT and bout 2 supra-LT, and 4) bout 1 supra-LT and bout 2 sub-LT. Sub-LT VO2 kinetics were similar whether the prior bout was supra- or sub-LT. The VO2 kinetics for supra-LT work preceded by a sub-LT “warm-up” were similar to those for supra-LT work that was not preceded by exercise (O-W warm-up): the “partial”: O2 deficit averaged 2.64 vs. 2.57 liters, and the “effective” VO2 time constant averaged 56 vs. 65 s. Exercise responses (i.e., the change between O W and minute 6 of exercise) were unaffected for lactate concentration (4.58 vs. 4.50 meq/l), pH (-0.08 vs. -0.10), and CO2 output (VCO2; 2.65 vs. 2.49 l/min). However, when the supra-LT work was preceded by a supra-LT warm-up, VO2 kinetics were appreciably faster (O2 deficit = 1.82 liters, VO2 time constant = 37 s) relative to 0-W warm-up; the lactate (0.69 meq/l), pH (-0.01), and VCO2 (2.08 l/min) responses were smaller; and the effective VCO2 time constant was longer (58 vs. 43 s). The mechanism(s) that underlie this speeding of the VO2 kinetics cannot be firmly established, but we suggest that an improved muscle perfusion during the exercise may be involved consequent to the residual metabolic acidemia from the high-intensity warm-up.

Muscular work can only be sustained if two transport chains function effectively: the electron transport chain and the oxygen transport chain. These may be considered to be “linked” at cytochrome oxidase. This chapter focuses on the effective functioning of the primary systems that comprise the oxygen transport chain in humans; the effective function of the electron transport chain is considered elsewhere (Chap. 71).

In the steady state of dynamic muscular exercise in humans, blood flow to exercising muscles (QM) increases essentially linearly with respect to work rate and oxygen uptake (VO2). The profiles of the nonsteady state QM response however are poorly understood, reflecting in large part the technical difficulties of accurately determining limb blood flow during periods of rapid change. Previous attempts to establish QM kinetics have been hampered by uncertainties relating to the assumptions of the techniques. For example, the constant indicator infusion approach assumes that the indicator is uniformly dispersed throughout the flow pulse, and none is lost prior to reaching the sampling site. Also, “standard” Doppler estimates of flow from blood velocity assume both that the focus of the beam on to the vessel and the vessel geometry itself remain unchanged throughout the exercise — with no assurance, of course, that they are. The duplex Doppler technique, in contrast, is not prey to these assumptions as it (a) visualizes the vessel throughout the measurement and (b) determines the vessel diameter and therefore can establish blood flow in addition to velocity (3,4) — assuming only that the vessel cross-section is circular.

The degree of the metabolic stress associated with muscular exercise depends on the intensity of the work being performed. Consequently, the gas exchange, acid/base and ventilatory requirements will also be intensity dependent. Low intensity exercise can be performed utilising ATP formed aerobically through oxidative phosphorylation but supplemented from creatine phosphate stores utilisation. When heavy exercise is undertaken, anaerobic glycolysis further supplements the high energy phosphate transformation with the consequent production of lactic acid — which at cellular pH is dissociated virtually entirely into lactate ions (La−) and protons (H+). The consequent H+ is predominantly buffered by bicarbonate ions (HCO3 −): the resulting carbonic acid yields extra carbon dioxide to be excreted by the lungs in addition to that produced from cellular respiration. The level of oxygen uptake at which lactate increases has been termed the Anaerobic or Lactate Threshold (LT).

We examined the kinetics of VO2, VCO2, and VE following the onset of unloaded leg cycling, and in recovery, in six patients with spinal cord injury (SCI). Exercise was produced by functional electrical stimulation (FES) of the quadriceps, hamstrings, and gluteal muscles. End-exercise VO2 (1.03 +/- 0.16 l.min-1), VCO2 (1.20 +/- 0.22 l.min-1) and VE (41 +/- 10 l.min-1) were elevated compared to values typically seen in healthy ambulatory subjects performing similar unloaded cycling. Mean response times for the on transients (MRTon) were both long and variable across subjects for VO2 (165 +/- 62 s), VCO2 (173 +/- 58 s), and VE (202 +/- 61 s). Recovery kinetics showed much less intersubject variability, and for five of six subjects were faster than the equivalent exercise MRT for all three variables (MRToff for VO2 of 103 +/- 28 s, VCO2 136 +/- 20 s, and VE 144 +/- 34 s), but P0.05 for all three. Size of the O2 deficit (1.96 +/- 0.90 l) and end-exercise lactate (7.05 +/- 1.65 mmol.l-1) were similar to values reported for healthy sedentary subjects performing maximal voluntary exercise, but the end-exercise heart rate (102 +/- 16 bpm) was lower than expected for this intensity of exercise. In conclusion, FES-induced unloaded cycling leads to exaggerated responses of pulmonary gas exchange and long time constants in patients with SCI. The delayed kinetics may be due in part to a blunted increase in heart rate in addition to severe deconditioning.

This paper offers a brief synopsis of the five preceding papers which constitute the proceedings of the symposium "Mechanistic basis of the slow component of VO2 kinetics during heavy exercise." The key features have been taken from each paper and a coherent position regarding the site and potential underlying mechanisms for the "excess" VO2 is presented. The hypothesis is developed that some aspect of fiber type recruitment patterns might be responsible for this phenomenon. Elucidation of the precise determinants of VO2 during heavy exercise is fundamental to our understanding of muscle energetics. Furthermore, certain patient populations, whose exercise tolerance is limited by impaired cardiovascular and/or respiratory capacity, may benefit from interventions designed to constrain the magnitude of the VO2 slow component.

During constant-load exercise of moderate intensity, pulmonary O2 uptake (VO2) is characterized by two temporal response components. The first occurs during the transit delay from the exercising limbs and is mediated predominantly by increased pulmonary blood flow. Thereafter, this response is supplemented by the influence of increased O2 extraction, causing VO2 to increase monoexponentially to its steady state, with a time constant that does not vary appreciably with work rate, at this intensity. At work rates that engender a lactic acidosis, however, an additional slow phase of VO2 is superimposed upon the underlying kinetics: this is of delayed onset and prolongs the time to steady state over the range within which the increases in blood lactate and [H+] stabilize or even decrease (heavy exercise). At higher work rates (severe exercise) a steady state is unattainable, with the VO2 trajectory resulting in VO2max progressively earlier the higher the work rate: it is therefore a fundamental determinant of exercise tolerance. Although the kinetic features of this slow VO2 component (other than its delay) remain to be determined, current evidence suggests that it is manifest predominantly in the exercising limbs, with the recruitment profile and metabolic features of fast-twitch fiber activation being the major contributor.

1. We determined the kinetics of cardiac output (Q) with respect to oxygen uptake (VO2) at the on- and off-transients of constant-load exercise. Six subjects performed constant-load exercise which consisted of 5 min rest, 5 min one-legged pedalling at 50 W and a 5 min recovery period. 2. The transient responses were characterized by first-order kinetics. There was no significant difference between the time constants for VO2 (tau VO2) at the on- (33.9 +/- 3.5 s, mean +/- S.E.M.) and off-transient (37.2 +/- 2.9 s). The time constant for Q (tau Q, 29.4 +/- 3.2 s) was consistently shorter than tau VO2 at the on-transient. However, tau Q was appreciably longer at the off-transient (44.3 +/- 3.6 s) than the on-transient. 3. The results support the contention that the time constant for the on-transient of Q is appreciably faster than that for VO2 and hence there seems little justification for the notion that the time constants for the kinetics of VO2 are determined by the limitations of blood flow in the transient. The asymmetry of Q kinetics, with the off-transient tau Q being appreciably slower than the on-transient tau Q, serves to maintain a sufficiently high oxygen flow to the muscle during recovery from exercise at a time when the muscle oxygen uptake remains high.

Exercise intolerance results when a subject is unable to sustain a required work rate sufficiently long for the successful completion of the task. The ability to sustain muscular exercise depends in large part on the ability to transport oxygen to its site of utilization as the terminal oxidant of the mitochondrial electron transport chain. This requires a coordinated interaction of skeletal muscle energetics and cardiovascular and pulmonary responses to the task. This article considers the fundamentals of the normal operation of these systems and their patterns of response to particular stress profiles to provide a frame of reference for the normalcy of responses to exercise testing.

Estimates of the proportional contribution of the peripheral chemoreceptors (i.e., the carotid bodies) to human ventilatory control during moderate exercise (i.e., below the lactate threshold, theta L) suggest that they: (a) exert no discernible influence on the initial (usually rapid) phase I component; (b) provide significant modulation of the slower, exponential phase II dynamics, therefore contributing to the tightness of arterial PCO2 regulation and the magnitude of the transient hypoxemia in this phase; and (c) account for approximately 20% of the steady-state phase III drive, which can rise to over 50% in hypoxia (PaO2 approximately 50 mm Hg). Above theta L, the carotid bodies constrain the transient fall in arterial pH by mediating much (but not all) of the compensatory hyperventilation for the metabolic acidemia. The carotid body contribution above theta L, estimated by Dejours O2 testing, is not appreciably different from subthreshold estimates, suggesting that: (a) the respiratory alkalosis in blood and cerebrospinal fluid resulting from the hyperventilation may suppress carotid chemosensitivity; (b) an artifact resulting from secondary hyperoxia-induced stimulation of central chemoreceptors may lead to underestimation of the carotid body contribution; or (c) the carotid bodies may not be entirely "silenced" by hyperoxia during a metabolic acidemia.

We have developed a method for simulating respiratory gas exchange for on-line calibration of metabolic measurement systems. It utilizes a pump which intakes a mixture of atmospheric air and a known flow of precision-analysed calibration gas (21% CO2, 79% N2). It expels the resulting mixture with flow wave form and profiles of gas concentration which closely resemble those of normal expiration. Control of the calibration mixture's inflow allows the investigator to set any desired metabolic rate regardless of the minute ventilatory rate. This separation of metabolic from ventilatory rates provides a stringent test of the computational performance of the respiratory gas exchange measurement systems. The apparatus can reproduce any range of respiratory and metabolic performance (currently ranging from 0.2-5 l.min-1 O2 uptake and CO2 output) with accuracy +/- 2%.

We consider how the optimal selection of the profile of imposed work rate, coupled with rigorous, statistically justified analysis of the pattern of the pulmonary gas exchange response, makes it possible to assemble a control model incorporating the proportional role of the muscle, circulation, and gas stores. Gains, time constants, and delays may be assigned to the components of the response and its linearity assessed. These techniques also allow the investigator to examine the features of poorly understood and even unexpected response patterns. Recent interest in the analysis of the non-steady state of exercise-in normal subjects and in patients with gas exchange defects-has led to an improved understanding of the sub-threshold dynamics. At work rates above the lactate threshold, the more complex kinetics are to date poorly described, and hence poorly understood, remaining a fertile area for the application of control-systems techniques to exercise.

The physiological requirements of performing exercise above the anaerobic threshold are considerably more demanding than for lower work rates. Lactic acidosis develops at a metabolic rate that is specific to the individual and the task being performed. Although numerous pyruvate-dependent mechanisms can lead to an elevated blood lactate, the increase in lactate during muscular exercise is accompanied by an increase in lactate/pyruvate ratio (i.e., increased NADH/NAD ratio). This is typically caused by an inadequate O2 supply to the mitochondria. Thus, the anaerobic threshold can be considered to be an important assessment of the ability of the cardiovascular system to supply O2 at a rate adequate to prevent muscle anaerobiosis during exercise testing. In this paper, we demonstrate, with statistical justification, that the pattern of arterial lactate and lactate/pyruvate ratio increase during exercise evidences threshold dynamics rather than the continuous exponential increase proposed by some investigators. The pattern of change in arterial bicarbonate (HCO3-) and pulmonary gas exchange supports this threshold concept. To estimate the anaerobic threshold by gas exchange methods, we measure CO2 output (VCO2) as a continuous function of O2 uptake (VO2) (V-slope analysis) as work rate is increased. The break-point in this plot reflects the obligate buffering of increasing lactic acid production by HCO3-. The anaerobic threshold measured by the V-slope analysis appears to be a sensitive index of the development of metabolic acidosis even in subjects in whom other gas exchange indexes are insensitive, owing to irregular breathing, reduced chemoreceptor sensitivity, impaired respiratory mechanics, or all of these occurrences.

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 FEV1, 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.