Kinetics of skeletal muscle O2 delivery and utilization at the onset of heavy-intensity exercise in pulmonary arterial hypertension.

Impaired O(2) delivery relative to O(2) demands at the onset of exercise might influence the response profile of muscle fractional O(2) extraction (≅Δ[deoxy-Hb/Mb] by near-infrared spectroscopy) either by accelerating its rate of increase or creating an "overshoot" (OS) in patients with pulmonary arterial hypertension (PAH). We therefore assessed the kinetics of O(2) uptake [Formula: see text] Δ[deoxy-Hb/Mb] in the vastus lateralis, and heart rate (HR) at the onset of heavy-intensity exercise in 14 females with PAH (connective tissue disease, IPAH, portal hypertension, and acquired immunodeficiency syndrome) and 11 age- and gender-matched controls. Patients had slower [Formula: see text] and HR dynamics than controls (τ[Formula: see text] = 62.7 ± 15.2 s vs. 41.0 ± 13.8 s and t (1/2)-HR = 61.3 ± 16.6 s vs. 43.4 ± 8.8 s, respectively; p < 0.01). No study participant had a significant reduction in oxyhemoglobin saturation. In OS(-) subjects (6 patients and 7 controls), the kinetics of Δ[deoxy-Hb/Mb] relative to [Formula: see text] were faster in patients (p = 0.05). Larger area under the OS and slower kinetics (MRT) of the "downward" component indicated greater O(2) delivery-to-utilization mismatch in OS(+) patients versus OS(+) controls (477.4 ± 330.0 vs. 78.1 ± 65.6 a.u. and 74.6 ± 18.8 vs. 46.0 ± 17.0 s, respectively; p < 0.05). Resting pulmonary vascular resistance was higher in OS(+) than OS(-) patients (23.1 ± 12.0 vs. 10.7 ± 4.0 Woods, respectively; p < 0.05). We conclude that microvascular O(2) delivery-to-utilization inequalities slowed the rate of adaptation of aerobic metabolism at the start of heavy-intensity exercise in women with PAH.

Haemodynamic effects of proportional assist ventilation during high-intensity exercise in patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Proportional assist ventilation (PAV) has been proposed as a more physiological modality of non-invasive ventilation, thereby reducing the potential for deleterious cardio-circulatory effects during exercise, in patients with COPD. We therefore evaluated whether PAV modulates the kinetic and 'steady-state' haemodynamic responses to exercise in patients with moderate-to-severe COPD. METHODS: Twenty patients underwent constant-load (75-80% peak work rate) cycle ergometer exercise testing to the limit of tolerance (T(lim)), while receiving PAV or breathing spontaneously. Stroke volume (SV), heart rate (HR) and cardiac output (CO) were monitored by impedance cardiography. RESULTS: Compared with unassisted breathing, PAV increased T(lim) in 8/20 patients (median improvement 113% (range 8 to 212) vs -20% (range -40 to -9)). PAV had no significant effects on 'steady-state' haemodynamic responses either in patients with or those without increased T(lim) (P > 0.05). However, at the onset of exercise, SV kinetics were slowed with PAV, in 13/15 patients with analysable data. HR dynamics remained unaltered or failed to accelerate sufficiently in nine of these patients, thereby slowing CO kinetics (T(1/2) 61 s (range 81-30) vs 89 s (range 100-47)). These deleterious effects were not, however, associated with PAV-induced changes in T(lim) (P > 0.05). CONCLUSIONS: PAV slowed the SV and CO kinetics at the onset of high-intensity exercise in selected patients with moderate-to-severe COPD. However, these adverse effects of PAV disappeared during the stable phase of exercise, and were not related to the ergogenic potential of PAV in this patient population.

Influence of respiratory pressure support on hemodynamics and exercise tolerance in patients with COPD.

Inspiratory pressure support (IPS) plus positive end-expiratory pressure (PEEP) ventilation might potentially interfere with the "central" hemodynamic adjustments to exercise in patients with chronic obstructive pulmonary disease (COPD). Twenty-one non- or mildly-hypoxemic males (FEV(1) = 40.1 +/- 10.7% predicted) were randomly assigned to IPS (16 cmH(2)O) + PEEP (5 cmH(2)O) or spontaneous ventilation during constant-work rate (70-80% peak) exercise tests to the limit of tolerance (T (lim)). Heart rate (HR), stroke volume (SV), and cardiac output (CO) were monitored by transthoracic cardioimpedance (Physioflow, Manatec, France). Oxyhemoglobin saturation was assessed by pulse oximetry (SpO(2)). At similar SpO(2), IPS(16) + PEEP(5) was associated with heterogeneous cardiovascular effects compared with the control trial. Therefore, 11 patients (Group A) showed stable or increased Delta "isotime" - rest SV [5 (0-29) mL], lower DeltaHR but similar DeltaCO. On the other hand, DeltaSV [-10 (-15 to -3) mL] and DeltaHR were both lower with IPS(16) + PEEP(5) in Group B (N = 10), thereby reducing DeltaCO (p < 0.05). Group B showed higher resting lung volumes, and T (lim) improved with IPS(16) + PEEP(5) only in Group A [51 (-60 to 486) vs. 115 (-210 to 909) s, respectively; p < 0.05]. We conclude that IPS(16) + PEEP(5) may improve SV and exercise tolerance in selected patients with advanced COPD. Impaired SV and CO responses, associated with a lack of enhancement in exercise capacity, were found in a sub-group of patients who were particularly hyperinflated at rest.

Kinetics of muscle deoxygenation are accelerated at the onset of heavy-intensity exercise in patients with COPD: relationship to central cardiovascular dynamics.

Patients with chronic obstructive pulmonary disease (COPD) have slowed pulmonary O(2) uptake (Vo(2)(p)) kinetics during exercise, which may stem from inadequate muscle O(2) delivery. However, it is currently unknown how COPD impacts the dynamic relationship between systemic and microvascular O(2) delivery to uptake during exercise. We tested the hypothesis that, along with slowed Vo(2)(p) kinetics, COPD patients have faster dynamics of muscle deoxygenation, but slower kinetics of cardiac output (Qt) following the onset of heavy-intensity exercise. We measured Vo(2)(p), Qt (impedance cardiography), and muscle deoxygenation (near-infrared spectroscopy) during heavy-intensity exercise performed to the limit of tolerance by 10 patients with moderate-to-severe COPD and 11 age-matched sedentary controls. Variables were analyzed by standard nonlinear regression equations. Time to exercise intolerance was significantly (P < 0.05) lower in patients and related to the kinetics of Vo(2)(p) (r = -0.70; P < 0.05). Compared with controls, COPD patients displayed slower kinetics of Vo(2)(p) (42 +/- 13 vs. 73 +/- 24 s) and Qt (67 +/- 11 vs. 96 +/- 32 s), and faster overall kinetics of muscle deoxy-Hb (19.9 +/- 2.4 vs. 16.5 +/- 3.4 s). Consequently, the time constant ratio of O(2) uptake to mean response time of deoxy-Hb concentration was significantly greater in patients, suggesting a slower kinetics of microvascular O(2) delivery. In conclusion, our data show that patients with moderate-to-severe COPD have impaired central and peripheral cardiovascular adjustments following the onset of heavy-intensity exercise. These cardiocirculatory disturbances negatively impact the dynamic matching of O(2) delivery and utilization and may contribute to the slower Vo(2)(p) kinetics compared with age-matched controls.

Clinical usefulness of response profiles to rapidly incremental cardiopulmonary exercise testing.

The advent of microprocessed "metabolic carts" and rapidly incremental protocols greatly expanded the clinical applications of cardiopulmonary exercise testing (CPET). The response normalcy to CPET is more commonly appreciated at discrete time points, for example, at the estimated lactate threshold and at peak exercise. Analysis of the response profiles of cardiopulmonary responses at submaximal exercise and recovery, however, might show abnormal physiologic functioning which would not be otherwise unraveled. Although this approach has long been advocated as a key element of the investigational strategy, it remains largely neglected in practice. The purpose of this paper, therefore, is to highlight the usefulness of selected submaximal metabolic, ventilatory, and cardiovascular variables in different clinical scenarios and patient populations. Special care is taken to physiologically justify their use to answer pertinent clinical questions and to the technical aspects that should be observed to improve responses' reproducibility and reliability. The most recent evidence in favor of (and against) these variables for diagnosis, impairment evaluation, and prognosis in systemic diseases is also critically discussed.

Effects of oxygen supplementation on cerebral oxygenation during exercise in chronic obstructive pulmonary disease patients not entitled to long-term oxygen therapy.

BACKGROUND: The rate of change (Δ) in cerebral oxygenation (COx) during exercise is influenced by blood flow and arterial O(2) content (CaO(2)). It is currently unclear whether ΔCOx would (i) be impaired during exercise in patients with chronic obstructive pulmonary disease (COPD) who do not fulfil the current criteria for long-term O(2) therapy but present with exercise-induced hypoxaemia and (ii) improve with hyperoxia (FIO(2) = 0·4) in this specific sub-population. METHODS: A total of 20 non-hypercapnic men (FEV(1) = 47·2 ± 11·5% pred) underwent incremental cycle ergometer exercise tests under normoxia and hyperoxia with ΔCOx (fold-changes from unloaded exercise in O(2)Hb) being determined by near-infrared spectroscopy. Pulse oximetry assessed oxyhaemoglobin saturation (SpO(2)), and impedance cardiography estimated changes in cardiac output (ΔQT). RESULTS: Peak work rate and ΔCOx in normoxia were lower in eight O(2) 'desaturators' compared with 12 'non-desaturators' (P < 0·05). Area under ΔCOx during sub-maximal exercise was closely related to SpO(2) decrements in 'desaturators' (r = 0·92, P < 0·01). These patients showed the largest improvement in peak exercise capacity with hyperoxia (P < 0·05). Despite a trend to lower sub-maximal ΔQT and mean arterial pressure with active intervention, ΔCOx was significantly improved only in this group (0·57 ± 0·20 versus 2·09 ± 0·42 for 'non-desaturators' and 'desaturators', respectively; P < 0·05). CONCLUSIONS: ΔCOx was impaired in non-hypoxaemic patients with COPD who desaturated during exercise. Hyperoxic breathing was able to correct for these abnormalities, an effect related to enhanced CaO(2) rather than improved central haemodynamics. This indicates that O(2) supplementation ameliorates exercise COx in patients with COPD who are not currently entitled to ambulatory O(2) therapy.

Effects of hyperoxia on the dynamics of skeletal muscle oxygenation at the onset of heavy-intensity exercise in patients with COPD.

This study addressed whether hyperoxia (HiOX=50% O2), compared to normoxia, would improve peripheral muscle oxygenation at the onset of supra-gas exchange threshold exercise in patients with chronic obstructive pulmonary disease (COPD) who were not overtly hypoxemic (resting Pa O2> 60 mmHg ). Despite faster cardiac output and improved blood oxygenation, HiOX did not significantly change pulmonary O2 uptake kinetics ( VO2p ). Surprisingly, however, HiOX was associated with faster fractional O2 extraction ( approximately Delta[deoxy-Hb+Mb] by near-infrared spectroscopy) (p<0.05). In addition, an "overshoot" in Delta[deoxy-Hb+Mb] was found after the initial fast response only in HiOX (7/11 patients) thereby suggesting impaired intra-muscular O2 delivery ( Q'O 2mv)-to-utilization. These data indicate that, despite improved "central" O2 delivery, Q'O2mv adapted at a slower rate than muscle VO2 under HiOX in non-hypoxaemic patients with COPD. Our results question the rationale of using supplemental O2 to improve muscle oxygenation during the transition to high-intensity exercise in this patient sub-population.