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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.

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.

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.

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.

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.

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 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.

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.

To determine the role of the peripheral chemoreceptors in mediating the hyperpnea associated with acute, nonocclusive inflation of a balloon in the main pulmonary artery of the conscious dog, we performed balloon inflations in awake and lightly anesthetized (chloralose-urethan) dogs before and after a) bilateral carotid body resection (CBR), b) cervical vagotomy (V), and c) after both CBR and V. In the intact awake state, balloon inflation increased VE from a mean of 4.91 to 7.16 1/min, usually within 1.5–2.0 min. Mean arterial PO2 decreased from 82 to 71 Torr and end-tidal PCO2 was reduced by 6 Torr. Arterial PCO2 and pH were unchanged in the steady state (as evidenced by discrete blood samples), even in those dogs in which VE increased up to 7.5 1/min. However, an indwelling PCO2 electrode in the femoral artery demonstrated a consistent transient elevation of arterial PCO2 prior to the steady state regulation. Vagotomy alone did not impair the ability to regulate PCO2 during balloon inflation. In some cases with CBR alone, arterial PCO2 was regulated at control levels in the steady state, but the transient increase during the early phase of balloon inflation was more marked (mean increase, 2 Torr). We conclude that the peripheral chemoreceptors are responsible for a significant component of the dynamic ventilatory behavior during this early phase (1.5–2.0 min) of acute maldistribution of VA/Q.

The ventilatory responses to diminished pulmonary blood flow (Qc), as a result of partial cardiopulmonary bypass (PCB), were studied in chloralose-urethan-anesthetized dogs. Qc was reduced by diverting vena caval blood through a membrane gas exchanger and returning it to the ascending aorta. PCB flows of 400--1,600 ml/min were utilized for durations of 2--3 min. Decreasing Qc, while maintaining systemic arterial blood gases and perfusion, results in a significant (P less than 0.05) decrease in expiratory ventilation (VE) (15.9%) and alveolar ventilation (VA) (31.0%). The ventilatory decreases demonstrated for this intact group persist after bilateral cervical vagotomy (Vx), carotid body and carotid sinus denervation (Cx), and combined Vx and Cx. The changes in VE and VA were significantly (P less than 0.001) correlated with VCO2 changes, r = 0.80 and r = 0.93, respectively. These ventilatory changes were associated with an overall average decrease in left ventricular PCO2 of 2.1 Torr; this decrease was significant (P less than 0.05) only in the intact and Cx groups. Decreasing pulmonary blood flow results in a decrease in ventilation that may be CO2 related; however, the exact mechanism remains obscure but must have a component that is independent of vagally mediated cardiac and pulmonary afferents and peripheral baroreceptor and chemoreceptor afferents.

The ventilatory response to venous CO2 loading and its effect on arterial CO2 tension was determined in five awake dogs. Blood, 200–500 ml/min, was diverted from a catheter in the right common carotid artery through a membrane gas exchanger and returned to the right jugular vein. CO2 loading was accomplished by changing the gas ventilating the gas exchanger from a mixture of 5% CO2 in air to 100% CO2. The ventilatory responses to this procedure were compared with those resulting from increased inspired CO2 concentrations (during which ventilation of the gas exchanger with the air and 5% CO2 mixture continued). The ventilatory response to each form of CO2 loading was computed as deltaVE/deltaPaco9. The mean ventilatory response to airway CO2 loading was 1.61 1/min per Torr PaCO2. The mean response for the venous CO2 loading was significantly higher and not significantly different from “infinite” CO2 sensitivity (i.e., isocapnic response). The results provide further evidence for a CO2-linked hyperpnea, not mediated by significant changes in mean arterial PCO2.

To investigate the role of the carotid bodies in regulating the bradycardia of breath holding in man, we studied heart rate (HR) responses to prolonged breath holding (BH) in five asymptomatic asthmatic patients whose carotid bodies had been resected (CBR). Seven normal subjects served as controls. BH experiments were randomly initiated with single breaths of 100%, 21%,or 12% 92. During BH with 21% O2, normal subjects displayed the typical bradycardia; this response, however, was attenuated with the other O2 concentrations. In contrast, the CBR subjects manifested BH tachycardia which was inversely proportional to the O2 tension. HR increased in be CBR group by 5%, 31%, and 45% during BH with 100%, 21%, and 12% O2, respectively. These results demonstrate that the bradycardia of BH in normal man is under the influence of the carotid bodies. During BH and in the absence of carotid bodies, an O2 tension-dependent tachycardia is unveiled.

Increased CO2 flow to the lung produced by increasing cardiac output (with constant PVCO2) results in hyperpnea with arterial PCO2 maintained at its control value (J. Appl. Physiol. 36: 457, 1974). To study if arterial PCO2 could be similarly regulated when CO2 flow was elevated by increasing PVCO2 (without changing cardiac output), we produced graded increases in PVCO2 (up to a mean of 69 mmHg) using an extracorporeal gas exchanger in five chloralose-urethan-anesthetized dogs. CO2 output increased up to fourfold. Ventilation increased in proportion to the additional CO2 flow to the lung with consequent regulation of arterial PCO2 at its control value. Comparable increases in VE produced by “conventional” airway loading resulted in arterial hypercapnia. The resulting CO2 response curve was similar to that found in unanesthetized dogs. We conclude that intravenous delivery of CO2 to the lung results in infinite “sensitivity” when computed as Delta VE/Delta paco2. These results provide evidence for a CO2-linked hyperpnea which is not mediated by measurable increases in mean arterial PCO2.

In order to determine the role of the carotid bodies on the ventilatory control characteristics during the non-steady-state phase of exercise in man, six normal males performed cycle ergometry with four repetitions of a 6 min, constant-load work bout at inspired O2 fractions (FI,O2) of 0.12, 0.15, 0.21, 0.30 and 1.00. Each test began with unloaded pedalling; this was followed by a constant load which was 90% of the subject's anaerobic threshold at FI,O2 = 0.12. Ventilation (VE), CO2 output (VCO2) and O2 uptake (VO2) were determined breath-by-breath during the test and the time constants of response (tau VE, tau VCO2 and tau VO2) were established by least-squares techniques, following interpolation (1 s), temporal alignment and averaging of the four responses. In each subject, tau VE and tau VCO2 increased as functions of increasing FI,O2, and were inverse functions of the proportional contribution to VE of peripheral chemoreceptor drive (as estimated from hyperoxic-transition or 'Dejours' tests). tau VE averaged 40 s at FI,O2 = 0.12 and 112 s at FI,O2 = 1.00, each response being well fitted by a single exponential. However, tau VO2 was not significantly affected by the alterations in FI,O2. Although there was no discernible peripheral chemosensitivity at FI,O2 = 0.30 or 1.00, the tau VE increased appreciably between these inspirates. We therefore conclude that the peripheral chemoreceptors are important, but not exclusive determinants of the exponential response characteristics during the non-steady-state phase of the exercise hyperpnoea in man. This supports the contention of a component of the control being humorally mediated even during moderate exercise.

The ventilatory effects of beta-adrenergic blockade during steady-state exercise were studied in eight normal subjects using intravenous propranolol hydrochloride (0.2 mg/kg). Heart rate decreased in all subjects by an average of 17%. Coincident with the phase of decreasing heart rate was a significant decrease in both minute ventilation (VE) and CO2 output (VCO2), averaging 9.6 and 9.2%, respectively. Both functions returned to prepropranolollevels after heart rate had reached its reduced steady-state value. The change in VE was significantly correlated with the change in VCO2 (r = 0.85, Pless than 0.005), and was associated with negligible changes in endtidal CO2 tensions and ventilatory equivalents for CO2. We interpret these studies as showing that the transient isocapnic hypopnea concomitant with an acute reduction in cardiac output was secondary to a transient decrease in CO2 flux (cardiac output x mixed venous CO2 content). This decrease in VE appearsto be induced by the acute decrease in cardiac output (“cardiodynamic hypopnea”), in fashion similar to the previously described cardiodynamic hyperpnea.

To determine the role of reflex discharge of afferent nerves from the working limbs in the exercise hyperpnea, 1.5- to 2.5-min periods of phasic hindlimb muscle contraction were induced in anesthetized cats by bilateral electrical stimulation of ventral roots L7, S1, and S2. Expired minute ventilation (VE) and end-tidal PCO2 (PETCO2) were computed breath by breath, and mean arterial PCO2 (PaCO2) was determined from discrete blood samples and, also in most animals, by continuous measurement with an indwelling PCO2 electrode. During exercise VE rose progressively with a half time averaging approximately 30 s, but a large abrupt increase in breathing at exercise onset typically did not occur. Mean PaCO2 and PETCO2 remained within approximately 1 Torr of control levels across the work-exercise transition, and PaCO2 was regulated at an isocapnic level after VE had achieved its peak value. Sectioning the spinal cord at L1-L2 did not alter these response characteristics. Thus, reflex discharge of afferent nerves from the exercising limbs was not requisite for the matching of ventilation to metabolic demand during exercise.

Twelve normal men performed 1-min incremental exercise tests to exhaustion in approximately 10 min on both treadmill and cycle ergometer. The maximal O2 uptake (VO2 max) and anaerobic threshold (AT) were higher (6 and 13%, respectively) on the treadmill than the cycle; the AT was reached at about 50% of VO2 max on both ergometers. Maximal CO2 output, heart rate, and O2 pulse were also slightly, but significantly higher on the treadmill. Maximal ventilation, gas exchange ratio, and ventilatory equivalents for O2 and CO2 for both forms of exercise were not significantly different. To determine the optimum exercise test for both treadmill and cycle, we exercised five of the subjects at various work rate increments on both ergometers in a randomized design. The treadmill increments were 0.8, 1.7, 2.5, and 4.2%/min at a constant speed of 3.4 mph, and 1.7 and 4.2%/min at 4.5 mph. Cycle increments were 15, 30, and 60 W/min. The VO2 max was significantly higher on tests where the increment magnitude was large enough to induce test durations of 8-17 min, but the AT was independent of test duration. Thus, for evaluating cardiopulmonary function with incremental exercise testing by either treadmill or cycle, we suggest selecting a work rate increment to bring the subject to the limit of his tolerance in about 10 min.

To investigate the importance of the major neural afferent component from the exercising extremities in exercise hyperpnea, rhythmic contraction of hindlimb muscles was produced in the dog, by electrically stimulating the peripheral cut ends of the sciatic and femoral nerves, bilaterally, for 4- to 5-min periods. VE, VCO2, and VO2 were computed breath-by-breath and PaCO2 was monitored continuously with an indwelling arterial electrode. During exercise, VO2 and VCO2 were approximately doubled in the steady state, rising with t1/2 of 25 +/- 2 and 35 +/- 4 s, respectively. VE increased within five breaths after exercise onset, and thereafter rose to a steady state with a t1/2 of 37 +/- 5 s. Mean PaCO2 increased transiently within the 1st min of stimulation but was not significantly different from control in the steady state. We conclude that the major neural afferent component from the contracting muscles is not an obligatory requirement for normal ventilatory response in the steady state of phasic exercise.

Ventilation and acid-base responses were studied at comparable levels of O2 uptake during cycle ergometer and treadmill exercise, to determine the extent to which the type of exercise affects these responses. Twenty male subjects performed 50-, 100-, and 150-W cycle ergometer exercise and three work rates of similar O2 uptake on a treadmill. At comparable oxygen uptakes, arterial lactate and VE were higher and arterial pH and bicarbonate were lower for cycle ergometer than treadmill exercise. These differences could be accounted for by the greater degree of metabolic acidosis during cycle ergometer work. The increment in VE over that predicted (from an extrapolation of the linear relationship of the VE-VO2 relationship for low work rates) was linearly related to the decrease in arterial bicarbonate; VE was increased by approximately 4 1/min for each meq/1 of bicarbonate decrease for both treadmill and cycle ergometry.

To investigate the contribution of vascular and metabolic stimuli to the sustained hyperpnea after exercise, the respiratory effects of obstructing and then releasing the femoral blood flow were recorded in 15 normal volunteers during recovery from steady-state cycle exercise (80 W). Obstruction was achieved using cuffs around the upper thighs, inflated for the first 2 min of recovery to a pressure of 200 mmHg. Cuff inflation significantly reduced ventilation during recovery compared with control (P less than 0.001); the subsequent release of pressure was accompanied by an increase in ventilation (averaging 3.2 l/min), which began on the first breath after release. This preceded a rise in end-tidal CO2 (maximum 8.3 Torr increase), which first became significant on the fourth breath after release and led to a further rise in ventilation. The first-breath increase in ventilation after cuff release persisted, although slightly attenuated (averaging 2.5 l/min), in additional experiments with inspired O2 fraction of 1.0. The pattern of ventilatory response was also similar when the experiments were performed with 5% CO2 in air as the inspirate. The immediate rise in ventilation on cuff release, together with the persistent response on 100% O2, suggests that the vascular changes resulting from cuff release exert an influence on ventilation independent of the effects of released metabolites on the known chemoreceptors. The persistence of the response on 5% CO2 indicates that CO2-sensitive lung afferents do not have a major role in these responses.

Pulmonary CO2 flow (the product of cardiac output and mixed venous CO2 content) is purported to be an important determinant of ventilatory dynamics in moderate exercise. Depletion of body CO2 stores prior to exercise should thus slow these dynamics. We investigated, therefore, the effects of reducing the CO2 stores by controlled volitional hyperventilation on cardiorespiratory and gas exchange response dynamics to 100 W cycling in six healthy adults. The control responses of ventilation (VE), CO2 output (VCO2), O2 uptake (VO2), and heart rate were comprised of an abrupt increase at exercise onset, followed by a slower rise to the new steady state (t1/2 = 48, 43, 31, and 33 s, respectively). Following volitional hyperventilation (9 min, PETCO2 = 25 Torr), the steady-state exercise responses were unchanged. However, VE and VCO2 dynamics were slowed considerably (t1/2 = 76, 71 s) as PETCO2 rose to achieve the control exercise value. VO2 dynamics were slowed only slightly (t1/2 = 39 s), and heart rate dynamics were unaffected. We conclude that pulmonary CO2 flow provides a significant stimulus to the dynamics of the exercise hyperpnea in man.

We determined the role of blood flow-induced changes in CO2 load to the lungs on ventilatory control, at rest and in the steady-state of electrically induced exercise, in the anesthetized dog. A portion of the vena caval blood was diverted to the descending aorta following “arterialization” through an extracorporeal gas exchanger. Ventilation typically decreased, both at rest and during exercise (i.e., at 2 different levels of mixed venous CO2), in proportion to the CO2 loss; arterial PCO2 was consequently regulated. There were concomitant increases of the pulmonary and peripheral vascular resistance. Bilateral cervical vagosympathectomy markedly attenuated the ventilatory response at rest, thus disrupting arterial PCO2 homeostasis, but not so during exercise. The results therefore provide evidence for and support the suggestion of CO2 flow-related hyperpnea both at rest and during muscular exercise.

All of the most widely-cited studies for the prediction of maximum exercise responses have utilized either volunteers or referred subjects. Therefore, selection bias, with overestimation of the reference values, is a likely consequence. In order to establish a set of predictive equations for the gas exchange, ventilatory and cardiovascular responses to maximum ramp-incremental cycle ergometry, this study prospectively evaluated 120 sedentary individuals (60 males, 60 females, aged 20-80), randomly-selected from >8,000 subjects. Regular physical activity pattern by questionnaire, body composition by anthropometry and dual energy X-ray absorptiometry (n = 75) and knee strength by isokinetic dynamometry were also assessed. Previously reported equations typically overestimated the subjects' peak oxygen uptake (p