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BACKGROUND: Exercise stress testing (EST) in patients with poor functional capacity measured by time on treadmill is typically deemed inconclusive and usually leads to further downstream testing. The aim of this study was firstly to evaluate the maximum rate pressure product (MRPP) during initial EST to assessthe need for follow-up testing; and secondly to investigate if MRPP is better than age predicted maximum heart rate (APMHR) for diagnostic outcome based on follow up cardiovascular (CV) events in patients with inconclusive EST due to poor functional capacity. METHODS: From a total of 2761 tests performed, 236 tests were considered inconclusive due to poor functional capacity which were available for analysis. From receiver operating characteristic (ROC) analysis, a cut-off value for MRPP of 25000 was chosen using CV events as the outcome measure (sensitivity 97%, specificity 45%). Cases were then categorised into those with an MRPP > 25000 and < 25000. RESULTS: Regardless of treadmill time, any patient attaining an MRPP > 25000 had no abnormal downstream testing or CV events at 2 years follow-up. On ROC analysis MRPP outperformed APMHR for sensitivity and specificity (area under curve 0.76 vs. 0.59, respectively). CONCLUSIONS: The results suggest that regardless of functional capacity, individuals whose EST is terminated at maximal fatigue, with no electrocardiogram evidence or symptoms of myocardial ischemia and yields an MRPP > 25000, do not require further downstream testing. Furthermore, this group of patients, while not immune to future CV events, have significantly better outcomes than those not attaining a MRPP > 25000.

Chest wall strapping has been used to assess mechanisms of dyspnea with restrictive lung disease. This study examined the hypothesis that dyspnea with restriction depends principally on the degree of reflex ventilatory stimulation. We compared dyspnea at the same (iso)ventilation when added dead space provided a component of the ventilatory stimulus during exercise. Eleven healthy men undertook a randomized controlled crossover trial that compared four constant work exercise conditions: 1) control (CTRL): unrestricted breathing at 90% gas exchange threshold (GET); 2) CTRL+dead space (DS): unrestricted breathing with 0.6-l dead space, at isoventilation to CTRL due to reduced exercise intensity; 3) CWS: chest wall strapping at 90% GET; and 4) CWS+DS: chest strapping with 0.6-l dead space, at isoventilation to CWS with reduced exercise intensity. Chest strapping reduced forced vital capacity by 30.4 ± 2.2% (mean ± SE). Dyspnea at isoventilation was unchanged with CTRL+DS compared with CTRL (1.93 ± 0.49 and 2.17 ± 0.43, 0–10 numeric rating scale, respectively; P = 0.244). Dyspnea was lower with CWS+DS compared with CWS (3.40 ± 0.52 and 4.51 ± 0.53, respectively; P = 0.003). Perceived leg fatigue was reduced with CTRL+DS compared with CTRL (2.36 ± 0.48 and 2.86 ± 0.59, respectively; P = 0.049) and lower with CWS+DS compared with CWS (1.86 ± 0.30 and 4.00 ± 0.79, respectively; P = 0.006). With unrestricted breathing, dead space did not change dyspnea at isoventilation, suggesting that dyspnea does not depend on the mode of reflex ventilatory stimulation in healthy individuals. With chest strapping, dead space presented a less potent stimulus to dyspnea, raising the possibility that leg muscle work contributes to dyspnea perception independent of the ventilatory stimulus. NEW & NOTEWORTHY Chest wall strapping was applied to healthy humans to simulate restrictive lung disease. With chest wall strapping, dyspnea was reduced when dead space substituted for part of a constant exercise stimulus to ventilation. Dyspnea associated with chest wall strapping depended on the contribution of leg muscle work to ventilatory stimulation. Chest wall strapping might not be a clinically relevant model to determine whether an alternative reflex ventilatory stimulus mimics the intensity of exertional dyspnea.

Exercise stress echocardiograms (ESEs) are a functional cardiovascular (CV) test typically used for the investigation of coronary artery disease. ESEs are often terminated at a predetermined age-predicted maximum heart rate (APMHR) to facilitate timely acquisition of ultrasound images at peak exercise. Although an APMHR of 85% is often used, this has not been validated as a suitable termination end point. Heart rate blood pressure product (HRBPP) as an established measure of myocardial work may provide a more reliable assessment of cardiac workload. The aim of this study was to assess maximal HRBPP (MHRBPP) and APMHR as markers of cardiac workload during ESE, using CV events at mean follow-up as the outcome variable. After exclusions, 712 patients being investigated for ischemic heart disease, performed an ESE to volitional fatigue using the standard Bruce protocol. Patient demographics and test data were collected and patients followed for 4.4 ± 2.1 years. Cut-points for MHRBPP (25,060; area under curve 0.77) and APMHR (93.8% and 97.9%; area under curve 0.71; p = 0.12 for difference) were established from receiver operating characteristic analysis. Those achieving an APMHR85% but MHRBPP25,060 had significantly more CV events than achieving an MHRBPP25,060 regardless of APMHR (p0.05). In conclusion, the current study demonstrates the superior prognostic power of MHRBPP over APMHR alone for the prediction of future CV events in patients performing an otherwise negative ESE for the detection of myocardial ischemia.

Most of the current guidelines for pulmonary rehabilitation recommend higher, over lower, intensity exercise training for COPD. Typically, we consider intensity of exercise training to be a key component of any exercise training programme. Whilst studies of young individuals have demonstrated that higher exercise training intensity results in greater improvements in exercise capacity, the evidence for older patients is not so clear cut. In COPD, there is limited evidence regarding the optimal intensity of exercise training. Using both physiological (peak exercise capacity) and patient-centred (e.g. quality of life) outcomes, it remains inconclusive if higher intensity exercise training bestows any greater benefit than low-intensity exercise. If we examine the data from interval training studies, which used both high- and low-intensity interval and continuous exercise, we are able to generate more data for comparison. Unfortunately, these data are challenging to interpret due to heterogeneity in how interval training was prescribed. However, when we normalize the interval training data for training volume and examine the change in peak cycling power, there is a relationship between training intensity and increase in peak power (Wpeak, r = 0.68, P

Background and objectiveThe mechanism of dyspnoea associated with pleural effusion is uncertain. A cohort of patients requiring thoracoscopy for unilateral exudative effusion were investigated for associations between dyspnoea and suggested predictors: impaired ipsilateral diaphragm movement, effusion volume and restricted lung inflation.MethodsBaseline Dyspnoea Index, respiratory function, and ultrasound assessment of ipsilateral diaphragm movement were assessed prior to thoracoscopy, when effusion volume was measured. Transitional Dyspnoea Index (change from baseline) was assessed 4 and 8 weeks after thoracoscopy. Pearson product moment assessed bivariate correlations and a general linear model examined how well total lung capacity (measuring restricted lung inflation), effusion volume and impaired diaphragm movement predicted Baseline Dyspnoea Index. Un-paired t tests compared the groups with normal and impaired diaphragm movement.Results19 patients were studied (14 malignant etiology). Total lung capacity was associated with Baseline Dyspnoea Index (r = 0.68, P = 0.003). Effusion volume (r = -0.138, P = 0.60) and diaphragm movement (P = 0.09) were not associated with Baseline Dyspnoea Index. Effusion volume was larger with impaired diaphragm movement compared to normal diaphragm movement (2.16 +/- SD 0.95 vs.1.16 +/- 0.92 L, P = 0.009). Total lung capacity was lower with impaired diaphragm movement compared to normal diaphragm movement (65.4 +/- 10.3 vs 78.2 +/- 8.6% predicted, P = 0.011). The optimal general linear model to predict Baseline Dyspnoea Index used total lung capacity alone (adjusted R-2 = 0.42, P = 0.003). In nine participants with controlled effusion, baseline effusion volume (r = 0.775, P = 0.014) and total lung capacity (r = -0.690, P = 0.040) were associated with Transitional Dyspnoea Index.ConclusionsRestricted lung inflation was the principal predictor of increased dyspnoea prior to thoracoscopic drainage of effusion, with no independent additional association with either effusion volume or impaired ipsilateral diaphragm movement. Restricted lung inflation may be an important determinant of the dyspnoea associated with pleural effusion.

AB PURPOSE: To test the reliability of Timed Up and Go Tests (TUGTs) in cardiac rehabilitation (CR) and compare TUGTs to the 6-Minute Walk Test (6MWT) for outcome measurement. METHODS: Sixty-one of 154 consecutive community-based CR patients were prospectively recruited. Subjects undertook repeated TUGTs and 6MWTs at the start of CR (start-CR), postdischarge from CR (post-CR), and 6 months postdischarge from CR (6 months post-CR). The main outcome measurements were TUGT time (TUGTT) and 6MWT distance (6MWD). RESULTS: Mean (SD) TUGTT1 and TUGTT2 at the 3 assessments were 6.29 (1.30) and 5.94 (1.20); 5.81 (1.22) and 5.53 (1.09); and 5.39 (1.60) and 5.01 (1.28) seconds, respectively. A reduction in TUGTT occurred between each outcome point (P

The 6-minute walk test (6MWT) is a common outcome measurement in cardiac rehabilitation. However, a search of the literature found no established guidelines for use of the 6MWT in cardiac rehabilitation.Systematic review of the validity, reliability and responsiveness of the 6MWT in cardiac rehabilitation.OvidMEDLINE, SPORTdiscus, EMBASE, CINAHL, Cochrane Reviews and Cochrane Clinical Trials between January 1948 and April 2011.Studies using 6MWTs in subjects with coronary artery disease undergoing cardiac rehabilitation on an outpatient basis, published in English, were included. STUDY APPRAISAL AND METHODS: Quantitative and qualitative analyses were conducted, including quality assessment of methodology, meta-analysis and assessment against level of evidence criteria.Fifteen articles met the inclusion criteria. One high-quality study was identified for reliability, six high-quality studies were identified for validity and 11 high-quality studies were identified for responsiveness. The meta-analysis found strong evidence that the 6MWT was responsive to change in clinical status following cardiac rehabilitation, with an estimated mean difference in 6-minute walk distance of 60.43m (95% confidence interval 54.57 to 66.30m; P0.001). Qualitative analysis indicated moderate evidence for repeatability of the 6MWT in patients undergoing cardiac rehabilitation, for a 2% to 8% learning effect between repeated 6MWTs, for a relationship between peak heart rate during the 6MWT and during cycle exercise at the ventilatory threshold, and for moderate-to-high correlation between the 6-minute walk distance and maximum metabolic equivalents achieved on symptom-limited exercise tests.Few studies assessed similar aspects of validity for the 6MWT.Strong evidence suggests that the 6MWT is responsive to clinical change following cardiac rehabilitation. Intra- and intertester reliability of the 6MWT and its validity in patients undergoing cardiac rehabilitation requires further research.

OBJECTIVES: The purpose of this study was to compare the effectiveness of moderate-intensity stationary cycling and walking exercise programmes in the early postoperative period after first-time coronary artery bypass graft surgery. METHODS: In this prospective trial, 64 patients (57 men, 7 women, mean age = 66 ± 9 years) performed twice daily, moderate-intensity exercise sessions, of 10-min duration, from postoperative day 3 until discharge from hospital. Patients were randomly assigned to stationary cycling or walking exercise intervention groups. Preoperative and discharge functional exercise capacity and health-related quality of life were assessed using 6-min walk and cycle assessments and the SF-36 version 2.0 questionnaire. Compliance with exercise was calculated as the proportion of scheduled exercise sessions completed. RESULTS: There were no significant differences between intervention groups at hospital discharge for 6-min walk distance (cyclists: 402 ± 93 m vs walkers: 417 ± 86 m, P= 0.803), 6-min cycle work (cyclists: 15.0 ± 6.4 kJ vs walkers: 14.0 ± 6.3 kJ, P= 0.798) or healthrelated quality of life. There was no significant difference between intervention groups for postoperative length of hospital stay (P= 0.335). Compliance rates for intervention groups were cyclists: 185/246 (75%) scheduled exercise sessions completed vs walkers: 199/242 (82%) scheduled exercise sessions completed (P= 0.162). CONCLUSIONS: Stationary cycling provides a well-tolerated and clinically effective alternative to walking in the early postoperative period after coronary artery bypass graft surgery. The optimal frequency, intensity and duration of exercise in the early postoperative period require further investigation. (Clinical trials register: Australian New Zealand Clinical Trials Registry; identification number: ACTRN12608000359336; http://www.anzctr.org.au/trial_view.aspx?ID=82978).

Rationale: Opioids are commonly used to relieve dyspnea, but clinical data are mixed and practice varies widely. Objectives: Evaluate the effect of morphine on dyspnea and ventilatory drive under well-controlled laboratory conditions. Methods: Six healthy volunteers received morphine (0.07 mg/kg) and placebo intravenously on separate days (randomized, blinded). We measured two responses to a CO2 stimulus: (1) perceptual response (breathing discomfort; described by subjects as “air hunger”) induced by increasing partial pressure of end-tidal carbon dioxide (PetCO2) during restricted ventilation, measured with a visual analog scale (range, “neutral” to “intolerable”); and (2) ventilatory response, measured in separate trials during unrestricted breathing. Measurements and Main Results: We determined the PetCO2 that produced a 60% breathing discomfort rating in each subject before morphine (median, 8.5 mm Hg above resting PetCO2). At the same PetCO2 after morphine administration, median breathing discomfort was reduced by 65% of its pretreatment value; P < 0.001. Ventilation fell 28% at the same PetCO2; P < 0.01. The effect of morphine on breathing discomfort was not significantly correlated with the effect on ventilatory response. Placebo had no effect. Conclusions: (1) A moderate morphine dose produced substantial relief of laboratory dyspnea, with a smaller reduction of ventilation. (2) In contrast to an earlier laboratory model of breathing effort, this laboratory model of air hunger established a highly significant treatment effect consistent in magnitude with clinical studies of opioids. Laboratory studies require fewer subjects and enable physiological measurements that are difficult to make in a clinical setting. Within-subject comparison of the response to carefully controlled laboratory stimuli can be an efficient means to optimize treatments before clinical trials.

Few tasks are simpler to perform than a breath hold; however, the neural basis underlying this voluntary inhibitory behaviour, which must suppress spontaneous respiratory motor output, is unknown. Here, using blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI), we investigated the neural network responsible for volitional breath holding in 8 healthy humans. BOLD images of the whole brain (156 brain volumes, voxel resolution 3 × 3 × 3 mm) were acquired every 5.2 s. All breath holds were performed for 15 s at resting expiratory lung volume when respiratory musculature was presumed to be relaxed, which ensured that the protocol highlighted the inhibitory components underlying the breath hold. An experimental paradigm was designed to dissociate the time course of the whole-brain BOLD signal from the time course of the local, neural-related BOLD signal associated with the inhibitory task. We identified a bilateral network of cortical and subcortical structures including the insula, basal ganglia, frontal cortex, parietal cortex and thalamus, which are in common with response inhibition tasks, and in addition, activity within the pons. From these results we speculate that the pons has a role in integrating information from supra-brainstem structures, and in turn it exerts an inhibitory effect on medullary respiratory neurones to inhibit breathing during breath holding.

In many diseases across a range of pathologies (e.g., cardiopulmonary, neuromuscular, and cancer), chronic dyspnea, particularly on exertion, is a major debilitating symptom often associated with clinical anxiety/depression. This study aims to explore the interaction between mood state and exertional dyspnea in a healthy population. Following familiarization, 20 healthy subjects (27-54 years old) performed six 5-min treadmill tests on three separate days. On each day subjects viewed randomly assigned images designed to induce positive, negative, or neutral mood states (International Affective Picture System). For each condition, at minute intervals, subjects rated dyspnea (sensory and affective domains) in the first test and mood (valence and arousal domains) in the second test. Oxygen uptake (V̇o2, liters/min), carbon dioxide production (V̇co2, liters/min), ventilation (V̇e, liters/min), respiratory frequency (fR, beats/min), and heart rate (HR, bpm), were measured throughout the exercise. V̇o2, V̇co2, V̇e, HR, and fR were not statistically significantly different among the three mood states ( P > 0.05). Mood valence was significantly higher with parallel viewing of positive (last 2-min mean ± SE = 6.9 ± 0.2) compared with negative pictures (2.4 ± 0.2; P < 0.001). Both sensory and affective domains of dyspnea were significantly higher during negative (sensory: 5.6 ± 0.3; affective: 3.3 ± 0.5) compared with positive mood (sensory: 4.4 ± 0.4, P < 0.001; affective: 2.1 ± 0.4, P = 0.002). These findings suggest that positive mood alleviates both the sensory and affective domains of exertional dyspnea in healthy subjects. Thus the treatment of anxiety/depression in dyspenic populations could be a worthwhile therapeutic strategy in increasing symptom-limited exercise tolerance, thereby contributing to improved quality of life.

SummaryWe have examined the role of age on the continuous positive airway pressure (CPAP) levels required to treat two groups of elderly (n=70) and young (n=70) sleep apneic patients, matched for disease severity (apnea/hypopnea index), body mass index and neck circumference. Elderly patients required lower CPAP levels compared to young [mean (sd): 6.9(1.9)cm H2O and 9.4(3.5)cm H2O, respectively; P

Aims Breathlessness is a cardinal symptom of heart failure and the altered regulation of breathing is common. The contribution of abnormal central nervous system activity has not previously been investigated directly, although abnormal autonomic responses have been described. Our aim was to assess whether heart failure patients exhibit different patterns of regional brain activation after exercise stress. Methods We used positron emission tomography with (H2O)-O-15, to measure changes in regional cerebral blood flow (rCBF) and absolute global cerebral blood flow (gCBF) in 6 mate class II/III heart failure patients and 6 normal controls. Breathlessness (0-5 visual analogue scale) and respiratory parameters were measured at rest, after horizontal bicycle exercise and during isocapnic hyperventilation. CBF was measured in each condition in all subjects. Results Both groups were similarly breathless after exercise and the respiratory parameters were comparable. rCBF differences for the main comparison (exercise vs; hyperventilation) were: activation of the right frontal medial. gyrus (P < 0.001, Z = 4.90) and left precentral gyrus (P < 0.03, Z = 4.66) in controls but not in patients. Both groups had rCBF increases in the left anterior cingulate (P < 0.05, Z = 4.67) and right dorsal cingulate cortex (P < 0.05, Z = 4.66). The gCBF did not differ between exercise, isocapnic hyperventilation and rest in patients but, in controls, gCBF was greater after exercise compared to either isocapnic hyperventilation or rest. Conclusion Heart failure patients had a distinct pattern of regional cortical activity with exercise-induced breathlessness but unvarying CBF values between conditions. These central neural differences in activity may contribute to some features of heart failure, such as variability in symptoms and autonomic dysregulation. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.

In young people, a sleep-related reduction in the gain of the ventilatory chemoreflex feedback loop occurs; in the elderly, it has been reported that no sleep-related reduction occurs. A relatively high loop gain could contribute to periodic breathing and central sleep apnoea in the elderly. This study tested the hypothesis that ageing is associated with a reduction in the magnitude of the sleep-related decrease in the hypercapnic ventilatory response (HCVR). The HCVR was measured using a steady state method, awake and asleep, in groups (n = 10) of elderly (66-81 yrs) and young (23-35 yrs) nonapnoeics. Upper airway resistance was maintained close to wakefulness levels using continuous positive airway pressure (mean sleep-related increase in resistance: elderly 1.6 +/- 1.2 cmH2O L x s(-1), young 1.2 +/- 0.8 cmH2O x L x s(-1)). The sleep-related decrease in the HCVR was similar in the elderly and young groups (elderly: wake 0.14 +/- 0.06 and sleep 0.06 +/- 0.02 L min(-1) x kPa and young, wake 0.19 +/- 0.07 and sleep 0.10 +/- 0.04 L x min(-1) x kPa). Ageing per se was shown not to change the magnitude of the sleep-related decrease in hypercapnic ventilatory response. The authors speculate that age-related changes in the hypercapnic ventilatory response are unlikely to contribute to the increased prevalence of central sleep apnoea in the elderly.

Air hunger (uncomfortable urge to breathe) is a component of dyspnea (shortness of breath). Three human H215O positron emission tomography (PET) studies have identified activation of phylogenetically ancient structures in limbic and paralimbic regions during dyspnea. Other studies have shown activation of these structures during other sensations that alert the organism to urgent homeostatic imbalance: pain, thirst, and hunger for food. We employed blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine activation during air hunger. fMRI conferred several advantages over PET: enhanced signal-to-noise, greater spatial resolution, and lack of ionizing radiation, enabling a greater number of trials in each subject. Six healthy men and women were mechanically ventilated at 12–14 breaths/min. The primary experiment was conducted at mean end-tidal Pco2of 41 Torr. Moderate to severe air hunger was evoked during 42-s epochs of lower tidal volume (mean = 0.75 L). Subjects described the sensation as “like breath-hold,” “urge to breathe,” and “starved for air.” In the baseline condition, air hunger was consistently relieved by epochs of higher tidal volume (mean = 1.47 L). A control experiment in the same subjects under a background of mild hypocapnia (mean end-tidal PCO2= 33 Torr) employed similar tidal volumes but did not evoke air hunger, controlling for stimulus variables not related to dyspnea. During each experiment, we maintained constant end-tidal Pco2and PO2to avoid systematic changes in global cerebral blood flow. Whole-brain images were acquired every 5 s (T2*, 56 slices, voxel resolution 3 × 3 × 3 mm). Activations associated with air hunger were determined using voxel-based interaction analysis of covariance that compared data between primary and control experiments (SPM99). We detected activations not seen in the earlier PET study using a similar air hunger stimulus ( Banzett et al. 2000 ). Limbic and paralimbic loci activated in the present study were within anterior insula (seen in all 3 published studies of dyspnea), anterior cingulate, operculum, cerebellum, amygdala, thalamus, and basal ganglia. Elements of frontoparietal attentional networks were also identified. The consistency of anterior insular activation across subjects in this study and across published studies suggests that the insula is essential to dyspnea perception, although present data suggest that the insula acts in concert with a larger neural network.

We employed an associative learning paradigm to test the hypothesis that exercise hyperpnea in humans arises from learned responses forged by prior experience. Twelve subjects undertook a “conditioning” and a “nonconditioning” session on separate days, with order of performance counterbalanced among subjects. In both sessions, subjects performed repeated bouts of 6 min of treadmill exercise, each separated by 5 min of rest. The only difference between sessions was that all the second-to-penultimate runs of the conditioning session were performed with added dead space in the breathing circuit. Cardiorespiratory responses during the first and last runs (the “control” and “test” runs) were compared for each session. Steady-state exercise end-tidal Pco2was significantly lower ( P= 0.003) during test than during control runs for both sessions (dropping by 1.8 ± 2 and 1.4 ± 3 Torr during conditioning and nonconditioning sessions, respectively). This and all other test-control run differences tended to be greater during the first session performed regardless of session type. Our data provide no support for the hypothesis implicating associative learning processes in the ventilatory response to exercise in humans.

The genesis of dyspnea is complex. It appears to be related to central respiratory drive although prevailing leg fatigue could independently potentiate dyspnea. We hypothesized that experimentally induced leg fatigue generates more intense exertional dyspnea for a given level of ventilatory drive. Following familiarization, 19 healthy subjects (32.2 ± 7.6 yr; 11 men) performed a 5-min treadmill test (speed: ∼4 km/h; grade: ∼25%) on two separate days randomized between control (C) and experimentally induced leg fatigue (E) achieved by repeated knee extension against 40% body weight until task failure. Oxygen uptake (V̇o2, l/min), carbon dioxide output (V̇co2, l/min), ventilation (V̇e, l/min), and respiratory rate (fR) were measured breath by breath. Heart rate (HR) and perceived dyspnea intensity (0–10 numerical scale) were recorded continuously. Data were averaged over 30-s intervals. Exertional dyspnea during E was statistically significantly higher (E vs. C: 4.2 ± 0.2 vs. 3.4 ± 0.2, P < 0.001) and accompanied by a significant increase in V̇e (E vs. C: 61.7 ± 3.7 vs. 55.3 ± 2.8, P = 0.005) and fR (E vs. C: 26.7 ± 1.0 vs. 24.2 ± 1.3, P = 0.036). Dyspnea following E remained significantly higher after allowing for the V̇e confound (ANCOVA, P = 0.003). V̇o2, V̇co2, and HR were not significantly different between two conditions. However, the slopes for dyspnea vs. V̇o2 and dyspnea vs. V̇e were similar between E and C, which suggested that gain in dyspnea per unit change in V̇o2 or V̇e was not altered by leg fatigue. These findings support the hypothesis that the intensity of exertional dyspnea is exacerbated by peripheral afferent information from fatigued leg muscles.

1. Positron emission tomography (PET) was used to identify the neuroanatomical correlates underlying 'central command' during imagination of exercise under hypnosis, in order to uncouple central command from peripheral feedback. 2. Three cognitive conditions were used: condition I, imagination of freewheeling downhill on a bicycle (no change in heart rate, HR, or ventilation, V(I)): condition II, imagination of exercise, cycling uphill (increased HR by 12 % and V(I) by 30 % of the actual exercise response): condition III, volitionally driven hyperventilation to match that achieved in condition II (no change in HR). 3. Subtraction methodology created contrast A (II minus I) highlighting cerebral areas involved in the imagination of exercise and contrast B (III minus I) highlighting areas activated in the direct volitional control of breathing (n = 4 for both; 8 scans per subject). End-tidal P(CO(2)) (P(ET,CO(2))) was held constant throughout PET scanning. 4. In contrast A, significant activations were seen in the right dorso-lateral prefrontal cortex, supplementary motor areas (SMA), the right premotor area (PMA), superolateral sensorimotor areas, thalamus, and bilaterally in the cerebellum. In contrast B, significant activations were present in the SMA and in lateral sensorimotor cortical areas. The SMA/PMA, dorso-lateral prefrontal cortex and the cerebellum are concerned with volitional/motor control, including that of the respiratory muscles. 5. The neuroanatomical areas activated suggest that a significant component of the respiratory response to 'exercise', in the absence of both movement feedback and an increase in CO(2) production, can be generated by what appears to be a behavioural response.

We have determined whether changes in [Formula: see text]above and below eucapnia modulate the precision of the voluntary control of breathing. Twelve trained subjects performed a compensatory tracking task in which they had to maintain the position of a cursor (perturbed by a variable triangular forcing function) on a fixed target by breathing in and out of a spirometer (ventilatory tracking; at 10 l/min). Before each task, subjects hyperventilated for 5 min, and the end-tidal [Formula: see text]([Formula: see text]) was controlled; tracking was then performed separately at hypocapnia, eucapnia, and hypercapnia ([Formula: see text] ∼25, 37, and 43 Torr, respectively). Ventilatory tracking error was unchanged during hypocapnia ( P > 0.05) but was significantly worse during hypercapnia ( P < 0.003), compared with eucapnia; arm tracking error, performed as a control, was not significantly affected by[Formula: see text]( P > 0.05). In conclusion, ventilatory tracking performance is unaffected by the eucapnic[Formula: see text]. From this, we suggest that resting breathing in awake humans may be independent of chemical drives and of the prevailing [Formula: see text].

1. The role of supra-brainstem structures in the ventilatory response to inhaled CO2 is unknown. The present study uses positron emission tomography (PET), with infusion of H2(15)O, to measure changes in relative regional cerebral blood flow (rCBF) in order to identify sites of increased neuronal activation during CO2-stimulated breathing (CO2-SB) in awake man. 2. Five male volunteers were scanned during CO2-SB (mean +/- S.E.M.; end-tidal PCO2, 50.3 +/- 1.7 mmHg; respiratory frequency, 16.4 +/- 2.7 min-1; tidal volume, 1.8 +/- 0.2 l). As control, scans were performed during 'passive' isocapnic (elevated fraction of inspired CO2) positive pressure ventilation (end-tidal PCO2, 38.4 +/- 1.0 mmHg; respiratory frequency, 15.5 +/- 2.2 min-1; tidal volume, 1.6 +/- 0.2 l). With CO2-SB, all subjects reported dyspnoea. 3. The anatomical locations of the increases in relative rCBF (CO2-SB versus control) were obtained using magnetic resonance imaging. 4. Group analysis identified neuronal activation within the upper brainstem, midbrain and hypothalamus, thalamus, hippocampus and parahippocampus, fusiform gyrus, cingulate area, insula, frontal cortex, temporo-occipital cortex and parietal cortex. No neuronal activation was seen within the primary motor cortex (at sites previously shown to be associated with volitional breathing). 5. These results suggest neuronal activation within the limbic system; this activation may be important in the sensory and/or motor respiratory responses to hypercapnia in awake man.

1. The cardiorespiratory response to imagination of previously performed treadmill exercise was measured in six competitive sportsmen and six non-athletic males. This was compared with the response to a control task (imaging letters) and a task not involving imagination ('treadmill sound only'). 2. In athletes, imagined exercise produced increases in ventilation which varied within and between subjects. The mean maximal increase (11.71 min-1) was approximately 20% of the ventilatory response to actual exercise. This was primarily due to treadmill speed-related increases in respiratory frequency (mean maximal increase, 14.8 breaths min-1) and resulted in significant reductions in end-tidal PCO2 (mean maximal fall, 7 mmHg). These effects were greater (P < 0.01) than any observed during the control tasks. 3. Changes in heart rate (mean increase, 12 beats min-1) were not significantly different from those observed during the control tasks (P > 0.2). 4. In non-athletes, imagination of exercise produced no changes in cardiorespiratory variables. No significant differences were detected in subjective assessments of movement imagery ability between athletes and non-athletes (P = 0.17). 5. This study demonstrates that ventilatory effects, when observed, are specific to imagination of exercise. The greater likelihood of generating ventilatory responses in highly trained athletes, experienced in 'rhythmic' sports, may be related to awareness of breathing and its role in exercise imagination strategy. A volitional component of the response cannot be discounted.

1. The sensation of breathlessness increases when ventilation is reflexly stimulated but it is not clear whether different stimuli have specific effects in the genesis of this sensation. 2. Our aim was to compare subjective assessments of the intensity of breathlessness at the same levels of ventilation induced by different combinations of reflex ventilatory stimuli. 3. Against a background of progressive exercise (maximum workload 170 W) in 'blinded' normal naive subjects, normoxic hypercapnia (maximum end-tidal CO2, PET, CO2, 56 mmHg) or isocapnic hypoxia (minimum O2 saturation 88%) was induced to achieve levels of ventilation (maximum 60 l min-1) 'matched' with those resulting from a higher intensity of exercise alone. Subjective breathlessness was rated with a visual analogue scale. 4. For a given ventilation, compared with exercise alone, breathlessness scores were similar during hypercapnia and were lower during hypoxia. 5. These results do not support the idea that during exercise, hypercapnia or hypoxia has a specific role in the genesis of the sensation of breathlessness. 6. The findings are consistent with the hypothesis that the degree of reflex ventilatory activation, however achieved, is an important determinant of the intensity of perceived breathlessness in healthy humans.

1. The response of the diaphragm to both transcranial magnetic stimulation and electrical phrenic nerve stimulation was studied in thirteen normal subjects under conditions of either a 'reflex' drive to ventilation with inhaled CO2 or during volitional ventilation of similar magnitude. 2. The induced compound action potential in the diaphragm was recorded using an oesophageal electrode, and in some cases transdiaphragmatic pressure was recorded using oesophageal and gastric balloon catheters. 3. The response of the diaphragm to transcranial magnetic stimulation was invariably facilitated with volitional inspiration; there was either minimal or no response at functional residual capacity. 4. Facilitation with inspiration was also seen during a 'reflex' drive to ventilation with inhaled CO2 in the presumed absence of any volitional contribution to ventilation. A similar degree of facilitation was seen with voluntary ventilation of similar magnitude and pattern. 5. If the facilitation is predominantly a cortical phenomenon, then these results imply that there is a behavioural component in the previously supposed purely 'reflex' drive to ventilation with inhaled CO2. We also discuss the interpretation of these results if some of the facilitation occurs at the phrenic motoneurone.

Hypoxia increases cerebral blood flow (CBF), but it is unknown whether this increase is uniform across all brain regions. We used H215O positron emission tomography imaging to measure absolute blood flow in 50 regions of interest across the human brain ( n = 5) during normoxia and moderate hypoxia. Pco2 was kept constant (∼44 Torr) throughout the study to avoid decreases in CBF associated with the hypocapnia that normally occurs with hypoxia. Breathing was controlled by mechanical ventilation. During hypoxia (inspired Po2 = 70 Torr), mean end-tidal Po2 fell to 45 ± 6.3 Torr (means ± SD). Mean global CBF increased from normoxic levels of 0.39 ± 0.13 to 0.45 ± 0.13 ml/g during hypoxia. Increases in regional CBF were not uniform and ranged from 9.9 ± 8.6% in the occipital lobe to 28.9 ± 10.3% in the nucleus accumbens. Regions of interest that were better perfused during normoxia generally showed a greater regional CBF response. Phylogenetically older regions of the brain tended to show larger vascular responses to hypoxia than evolutionary younger regions, e.g., the putamen, brain stem, thalamus, caudate nucleus, nucleus accumbens, and pallidum received greater than average increases in blood flow, while cortical regions generally received below average increases. The heterogeneous blood flow distribution during hypoxia may serve to protect regions of the brain with essential homeostatic roles. This may be relevant to conditions such as altitude, breath-hold diving, and obstructive sleep apnea, and may have implications for functional brain imaging studies that involve hypoxia.

Background: While the acute physiological responses to continuous exercise have been well documented in individuals with chronic obstructive pulmonary disease (COPD), no previous study has examined the response to intermittent exercise in these patients. Methods: We examined the physiological responses of 10 individuals with moderate COPD (forced expiratory volume in 1 second 52 (15)% predicted) who performed both an intermittent (1 min exercise and rest intervals) and a continuous cycle ergometer test on separate days. Both intermittent and continuous exercise tests were performed at the same power output, calculated as 70% of the peak power attained during an incremental exercise test. Results: Intermittent exercise was associated with significantly lower values for oxygen uptake, carbon dioxide output, expired ventilation, heart rate, plasma lactate concentration, and ratings of breathlessness than continuous exercise. Subjects were able to complete a significantly greater total amount of work during intermittent exercise (71 (32) kJ) than during continuous exercise (31 (24) kJ). The degree of dynamic lung hyperinflation (change in end expiratory lung volume) was significantly lower during intermittent exercise (0.23 (0.07) l) than in continuous exercise (0.52 (0.13) l). Conclusions: The greater amount of work performed and lower measured physiological responses achieved with intermittent exercise may allow for greater peripheral training adaptations in individuals with more limited lung function. The results suggest that intermittent exercise may be superior to continuous exercise as a mode of training for patients with COPD.

Arousals from sleep result in hyperventilation and hypocapnia that can lead to sleep apnoea. We have investigated whether sleep apnoea in the elderly is associated with more arousals compared with younger people. Additionally, the impact of arousals on daytime symptoms was noted. Four groups (n = 11) of elderly (> 65 years) and young (< 39 years) apnoeic (EA and YA), and age-matched non-apnoeics (EN and YN) were studied. The arousal index (AI) and apnoea/hypopnoea index were determined from polysomnography. Sleepiness (Epworth Sleepiness Scale) and Quality of life (QoL, SF-36) were assessed. The mean (SD) AI was: EN 23.1 (7.6), EA 46.5 (8.8), YN 13.2 (6.6), YA 38.5 (12.1) events/h. AI was higher in the elderly (P = 0.002) and in apnoeics (P = 0.001); however, the increase in AI associated with sleep apnoea was not age dependent (P = 0.73). The influence of sleep apnoea on sleepiness was similar in both age groups. YA but not EA reported reduced physical functioning (P = 0.04), vitality (P = 0.007) and general health (P = 0.04) compared to non-apnoeics. We conclude that (1) the effect of sleep apnoea on arousal is no greater in the elderly compared to the young (2) despite similar levels of sleepiness, elderly apneoics perceive a reduced loss of QoL compared to younger patients.

There is broad agreement that the awake human ventilatory response to a moderate inspiratory load consists of a prolongation of inspiratory time (T(I)) with a maintenance of tidal volume (V(T)) and end-tidal P(C)(O(2)) (P(ET,C)(O(2))), the response being severely blunted in sleep. There is no agreement on the mechanisms underlying this ventilatory response. Six naive healthy males (aged 39-44) were studied supine with their heads in a positron emission tomography (PET) scanner to allow relative regional cerebral blood flow (rCBF) to be measured with H(2)(15)O given intravenously. A linearised resistive load (24 cmH(2)O (l s(-1))(-1)) could be added to the inspiratory limb of a breathing valve inserted into a tightly fitting facemask; inspiratory flow was measured with a pneumotachograph. The load was applied, without alerting the subject, when the radioactivity first reached the head. Six scans were performed with and without the load, in each subject. Relative rCBF contrasts between the loaded and unloaded breathing states showed significant activations in inferior parietal cortex, prefrontal cortex, midbrain, basal ganglia and multiple cerebellar sites. No activations were found in the primary sensorimotor cortex. The findings suggest that there is a pattern of motor behavioural response to the uncomfortable sensation that inspiration is impeded. This results in a prolongation of T(I), the maintenance of V(T) and a reduction in the degree of discomfort, presumably because of the reduction of mean negative pressure in the airways.

Increases in cerebral blood flow produced by vasoactive agents will increase blood oxygen level-dependent (BOLD) MRI signal intensity. The effects of such vasodilation on activation-related signal changes are incompletely characterized. The two signal changes may be simply additive or there may be more a complex interaction. To investigate this, BOLD MRI was performed in four normal male subjects using T2*-weighted echo planar imaging; brain volumes were acquired every 6.2 s, using a Siemens VISION scanner operating at 2 Tesla; each volume consisted of 64 sequential transverse slices (64 x 64 pixels per slice, 3 x 3 x 3 mm). Sixteen periods of visual stimulation were produced using a flickering checkerboard (8 Hz, 31 s On/31 s Off); this was coupled with five periods of hypercapnia (4% inspired CO(2), 62 s On/124 s Off). Data were analyzed using SPM96. Mean signal intensity, calculated globally for the whole brain, closely mirrored changes in the partial pressure of end-tidal CO(2) (PCO(2)), and hypercapnia was associated with widespread significant signal increases (P0.001), predominantly within grey matter. As expected, the visual stimulation produced significant signal changes within the occipital cortex (P0.001). Within the occipital cortex, no significant interactions (P0.001) between the effects of the visual stimulation and PCO(2) were present. The increases in PCO(2) imposed dynamically in the present study would increase cerebral blood flow by between 25 and 40%, an increase within the physiological range and comparable to that induced by neural activation. With this flow change the effects of vasodilation, on an activation-related signal change, are simply additive.

We investigated the effect of age on breathing and total pulmonary resistance (Rl) during sleep by studying elderly (>65 yr) and young (25–38 yr) people without sleep apnea (EN and YN, respectively) matched for body mass index (BMI). To determine the impact of sleep apnea on age-related changes in breathing, we studied elderly and young apneic patients (EA and YA, respectively) matched for apnea and BMI. In all groups ( n = 11), breathing during periods of stable sleep was analyzed to evaluate the intrinsic variability of respiratory control mechanisms. In the absence of sleep apnea, the variability of the breathing was similar in the elderly and young [mean (± SD) coefficient of variation (CV) of tidal volume (Vt); wake: EN 21.0 ± 14.9%, YN 14.7 ± 5.5%; sleep: EN 14.0 ± 6.0%; YN 11.5 ± 6.4%]. In patients with sleep apnea, breathing during stable sleep was more irregular, but there were no age-related differences (CV of Vt; wake: EA 22.0 ± 11.6%, YA 16.7 ± 11.3%; sleep: EA 32.8 ± 24.9%, YA 25.2 ± 16.3%). In addition, EN tended to have a higher Rl( n = 6, Rl midinspiration, wake: EN 7.1 ± 3.0; YN 9.1 ± 6.4 cmH2O · l−1 · s, sleep: EN 17.5 ± 11.7; YN 9.8 ± 2.0 cmH2O · l−1 · s). We conclude that aging per se does not contribute to the intrinsic variability of respiratory control mechanisms, although there may be a lower probability of finding elderly people without respiratory instability.

BACKGROUND—Breathlessness leading to exercise limitation is common in patients with advanced cancer and is ineffectively treated. There are few research data to guide clinicians on best practice. The shuttle walking test has been validated for some conditions such as chronic obstructive pulmonary disease but not for advanced cancer. One of the well documented difficulties of doing clinical research in palliative care is the acceptability of assessment tests. This study examined the reproducibility of the shuttle walking test in patients with advanced cancer to help facilitate the systematic evaluation of interventions designed to improve breathlessness. METHODS—Patients performed three shuttle walks on separate days with continuous monitoring of arterial oxygen saturation and heart rate; simple pulmonary function (FEV1) was also recorded. Data on quality of life, anxiety, and depression were collected throughout the study period using appropriate questionnaires. Breathlessness was measured before and after exercise using a visual analogue scale. RESULTS—Data from 22 patients were compared between visits 2 and 3. There were no significant differences between the FEV1 (1.89 v 1.90, p=0.73), distance walked on each test (245 m v 256 m, p=0.14), end-exercise levels of heart rate (107/min v 108/min, p=0.11), oxygen saturation (93.4% v 93.2%, p=0.38), or breathlessness scores (p=0.62) on the two occasions. Indices of quality of life, anxiety, and depression were also not different between the two tests. The investigation was very acceptable to patients, families, and staff. CONCLUSIONS—The shuttle walking test is a reproducible test of functional capacity in ambulant patients with advanced cancer, WHO performance status 1 or 2. The data indicate that a practice session is needed. It is easy to carry out and acceptable for patients with advanced cancer.

During sleep, changes in respiratory mechanics place additional demands on respiratory control mechanisms if adequate gas exchange is to be maintained. Loss of consciousness is accompanied by a reduction in efferent neural activity to both upper airway and respiratory pump muscles leading to potential decreases in inspiratory muscle force and increases in resistance to airflow (Orem et al. 1977; Remmers et al. 1978; Sauerland & Harper, 1981; Hudgel et al. 1984). When awake, an experimentally induced increase in the resistance to airflow typically leads to a prolongation of inspiratory duration of the first breath, resulting in a maintenance of tidal volume and ventilation, although some variation between individual responses can occur (Iber et al. 1982; Wilson et al. 1984; Hudgel et al. 1987; Wiegand et al. 1988; Badr et al. 1990). This immediate respiratory compensatory response appears to be almost lost during sleep such that imposition of a load is associated with an acute hypoventilation (Iber et al. 1982; Wilson et al. 1984; Hudgel et al. 1987; Wiegand et al. 1988; Gugger et al. 1989; Badr et al. 1990). However, the majority of studies supporting this observation have been carried out during non-rapid eye movement (NREM) sleep. The aim of the present study was to test the immediate respiratory response to an added inspiratory resistive load during REM sleep. The inability to compensate for a respiratory load is likely to be a particular problem during REM sleep because the respiratory mechanics are more compromised secondary to the occurrence of atonicity in some respiratory-related skeletal muscles (Pack, 1995). In healthy adults, observations of breathing during REM sleep have shown that it is often irregular (Bulow, 1963). In patients with sleep apnoea, REM sleep is associated with prolonged apnoeas (Findley et al. 1980) and in some cases apnoeas occur only during this sleep stage (Kass et al. 1996). In patients with chronic lung disease, sleep-disordered breathing is seen predominantly in REM sleep and is often associated with severe hypoxaemia (Douglas et al. 1979). One explanation for these observations is that the ability to mount a respiratory compensation to fluctuations in resistance is impaired during REM sleep. In the present study we wished to measure ventilation in response to an added inspiratory resistive load during REM sleep. In designing this study, we needed to consider the difficulties of making experimental interventions during REM sleep. This phase of sleep is characterised by skeletal muscle atonia and frequent episodes of rapid eye movement (phasic REM) interspersed with periods of no eye movements (tonic REM). Hypoventilation is known to be more pronounced during the relatively short (typically

Murphy, K., D. R. Corfield, A. Guz, G. R. Fink, R. J. S. Wise, J. Harrison, and L. Adams. Cerebral areas associated with motor control of speech in humans. J. Appl. Physiol. 83(5): 1438–1447, 1997.—We have defined areas in the brain activated during speaking, utilizing positron emission tomography. Six normal subjects continuously repeated the phrase “Buy Bobby a poppy” (requiring minimal language processing) in four ways: A) spoken aloud, B) mouthed silently, C) without articulation, and D) thought silently. Statistical comparison of images from conditions Awith C and B with D highlighted areas associated with articulation alone, because control of breathing for speech was controlled for; we found bilateral activations in sensorimotor cortex and cerebellum with right-sided activation in the thalamus/caudate nucleus. Contrasting images from conditions A with B and C with D highlighted areas associated with the control of breathing for speech, vocalization, and hearing, because articulation was controlled for; we found bilateral activations in sensorimotor and motor cortex, close to but distinct from the activations in the preceding contrast, together with activations in thalamus, cerebellum, and supplementary motor area. In neither subtraction was there activation in Broca’s area. These results emphasize the bilaterality of the cerebral control of “speaking” without language processing.

1. The sensation of an urge to breathe (air hunger) associated with a fixed level of hypercapnia is reduced when ventilation increases. The aim of the present study was to investigate whether pulmonary receptors are important in this mechanism. 2. Five heart-lung transplant (HLT) subjects and five control subjects were studied during periods of mechanical and spontaneous ventilation. End-tidal Pco2 (PET,CO2) was increased by altering the level of inspired CO2. Throughout, subjects rated sensations of air hunger. Air hunger was also monitored during and immediately following maximal periods of breath-holding. 3. When the level of mechanical ventilation was fixed, both groups experienced a high degree of air hunger when PET,CO2 was increased by about 10 mmHg. At similar levels of hypercapnia, both groups derived relief from approximately twofold increases in tidal volume, although relief was slightly less effective in HLT subjects. This was reversible, with decreases in the level of mechanical ventilation rapidly giving rise to increased ratings of air hunger. 4. With breath-holding, all subjects obtained some respiratory relief within 2 s of the break point; there was no significant difference between the groups. 5. The results suggest that sensations of an urge to breathe induced by hypercapnia can be modulated by changes in tidal volume in the presumed absence of afferent information from the lung.

The ventilatory response to electrically induced exercise (EEL) was studied in eighteen normal subjects and compared with the response to performing the same exercise voluntarily (EV). EEL was produced by surface electrode stimulation of the quadriceps and hamstring muscles so as to cause a pushing movement at 1 HZ against a spring load; this produced no pain or discomfort. Matching of EV to EEL was achieved by subjects copying a tension signal recorded during EEL and displayed on a storage oscilloscope. There were no differences between the resting states measured before either form of exercise. The ventilatory response (change in ventilation as a ratio of the change in CO2 elimination) was similar in the two types of exercise. The increases in ventilation and CO2 elimination were greater with EEL. Small but significant increases in the gas exchange ratio and serum lactate were found for EEL but not for EV, suggesting an increase in anaerobic metabolism in EEL. End-tidal PCO2 showed little change in either form of exercise. In some runs end-tidal PCO2 rose, but insufficiently to account for the ventilatory response as judged by the response to inhaled CO2. In two subjects arterial blood samples showed small and inconsistent changes in both Pa,CO2 and PaO2 for EV and EEL. pH and base excess changes also were consistent with more anaerobiosis with EEL compared to EV. The first ten breaths of exercise were used to study the on transient. In EV, expiratory duration shortened and ventilation increased significantly on the first breath but CO2 elimination did not increase until the second breath; in EEL, these variables did not change significantly until the second breath. For the remainder of the on transient the pattern of the ventilatory response was similar for EV and EEL. By the end of the on transient both EV and EEL had reached approximately 80% of their final steady-state values. These results suggest that a normal ventilatory response can occur in the absence of a drive to exercise from the cortex.

1. The ventilatory and circulatory responses to electrically induced leg exercise (EEL) were studied in seven normal subjects and compared with the responses to performing the same exercise voluntarily (EV). 2. EEL was produced by surface electrode stimulation of the quadriceps and hamstring muscle groups. This produced a push-relax pattern of exercise against a spring load and was free of any pain or discomfort. EV, at the same level, was achieved by subjects copying a display of timing and force information on a storage oscilloscope. 3. Cardiac output was estimated using validated Doppler ultrasound measurements of the velocity in the ascending aorta, combined with an estimate of aortic cross-sectional area using M-mode echocardiography. 4. Data from EV and EEL exercise runs were matched, within subjects, for the increase in oxygen consumption during the first 30 s of exercise; there were no significant differences between the resting states prior to either form of exercise. 5. The first ten beats of exercise were used to study the circulatory on-transient. The cardiac output responses to both EV and EEL were similar; however, in EV alone there was an initial significant drop in stroke volume and a slightly greater rise in heart rate. 6. The first five breaths of the response were used to study the ventilatory on-transient, and by measuring cardiac output, stroke volume and heart rate throughout each breath, the relationship between circulatory and ventilatory variables could be assessed. Ventilation showed a significantly greater rise at the onset of exercise during EV than during EEL; PET,CO2 (end-tidal CO2 pressure) showed small but significant falls for both EV and EEL. 7. The circulatory changes on a breath-by-breath basis are similar for EV and EEL although the ventilatory changes differ. In both EV and EEL the average increase in ventilation at the onset of exercise is proportionally greater than the average increases in cardiac output. Individual exercise runs show no particular relationship between circulatory and ventilatory change. 8. The results provide no support in man during mild leg exercise for a 'cardiodynamic' drive to breathing.

The ventilatory response to electrically induced exercise was studied in thirteen patients with traumatic spinal cord transection at or about the level of T6. The steady-state and on-transient responses to this exercise were compared with those obtained in eighteen normal subjects (Adams, Garlick, Guz, Murphy & Semple, 1984). Exercise was produced by surface electrode stimulation of the quadriceps and hamstring muscles so as to produce a pushing movement at 1 HZ against a spring load. At rest there was no significant difference between normals and patients, except that the patients had a lower CO2 elimination (VCO2) and end-tidal PCO2 (PET,CO2) and a higher heart rate. On exercise the mean rise in VCO2 for the patients was 172 ml min-1 (S.D. 72), and for the normals was 287 ml min-1 (S.D. 143). The corresponding mean changes in ventilation (VI) were 4.4 l min-1 (S.D. 2.2) and 7.6 l min-1 (S.D. 3.2). However, the ventilatory equivalent for CO2 (delta VI/delta VCO2) in the steady state was not significantly different between patients (26.0, S.D. 5.9) and normals (28.5, S.D. 7.4). In the steady state there was a mean rise in PET,CO2 of 0.9 mmHg (S.D. 1.4) in the normals, and 3.2 mmHg (S.D. 2.7) in the patients, but there was overlap between the two groups. In many experimental runs in both groups, PET,CO2 did not rise, and sometimes fell. Where PCO2 did rise, the ventilatory response to exercise could not be accounted for on the basis of the ventilatory sensitivity to CO2 inhalation. From arterial sampling in three of the patients it was found that when PET,CO2 rose, the corresponding change in Pa,CO2 was less. During the on transient, there was a significant rise in both VCO2 and VI by the second breath in both groups. At the end of the on transient the normal subjects had achieved 84% (S.D. 40) of the steady-state increase in VCO2 and 88% (S.D. 24) of the increase in VI. The corresponding values for the patients were 67% (S.D. 17) and 77% (S.D. 16) respectively; these differences between normals and patients are significant. The increase of VI during the on transient in the patients was achieved almost entirely by an increase in tidal volume whereas in normals, an increase in respiratory rate was a more important component. We conclude therefore that in man, spinal cord transection with a presumed loss of muscle afferents allows a ventilatory response to electrically induced exercise that cannot be explained by classical chemoreception.(ABSTRACT TRUNCATED AT 400 WORDS)