Patients with chronic obstructive pulmonary disease (COPD) have slowed pulmonary O2 uptake (V̇o2p) kinetics during exercise, which may stem from inadequate muscle O2 delivery. However, it is currently unknown how COPD impacts the dynamic relationship between systemic and microvascular O2 delivery to uptake during exercise. We tested the hypothesis that, along with slowed V̇o2p kinetics, COPD patients have faster dynamics of muscle deoxygenation, but slower kinetics of cardiac output (Q̇t) following the onset of heavy-intensity exercise. We measured V̇o2p, Q̇t (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 V̇o2p ( r = −0.70; P < 0.05). Compared with controls, COPD patients displayed slower kinetics of V̇o2p (42 ± 13 vs. 73 ± 24 s) and Q̇t (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 O2 uptake to mean response time of deoxy-Hb concentration was significantly greater in patients, suggesting a slower kinetics of microvascular O2 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 O2 delivery and utilization and may contribute to the slower V̇o2p kinetics compared with age-matched controls.

Background: Respiratory muscle unloading during exercise could improve locomotor muscle oxygenation by increasing oxygen delivery (higher cardiac output and/or arterial oxygen content) in patients with chronic obstructive pulmonary disease (COPD). Methods: Sixteen non-hypoxaemic men (forced expiratory volume in 1 s 42.2 (13.9)% predicted) undertook, on different days, two constant work rate (70-80% peak) exercise tests receiving proportional assisted ventilation (PAV) or sham ventilation. Relative changes (D%) in deoxyhaemoglobin (HHb), oxyhaemoglobin (O 2 Hb), tissue oxygenation index (TOI) and total haemoglobin (Hb tot ) in the vastus lateralis muscle were measured by nearinfrared spectroscopy. In order to estimate oxygen delivery (DO 2 est, l/min), cardiac output and oxygen saturation (SpO 2 ) were continuously monitored by impedance cardiography and pulse oximetry, respectively. Results: Exercise tolerance (Tlim) and oxygen uptake were increased with PAV compared with sham ventilation. In contrast, end-exercise blood lactate/Tlim and leg effort/Tlim ratios were lower with PAV (p,0.05). There were no between-treatment differences in cardiac output and SpO 2 either at submaximal exercise or at Tlim (ie, DO 2 est remained unchanged with PAV; p.0.05). Leg muscle oxygenation, however, was significantly enhanced with PAV as the exercise-related decrease in D(O 2 Hb)% was lessened and TOI was improved; moreover, D(Hb tot )%, an index of local blood volume, was increased compared with sham ventilation (p,0.01). Conclusions: Respiratory muscle unloading during highintensity exercise can improve peripheral muscle oxygenation despite unaltered systemic DO 2 in patients with advanced COPD. These findings might indicate that a fraction of the available cardiac output had been redirected from ventilatory to appendicular muscles as a consequence of respiratory muscle unloading.

Blood flow requirements of the respiratory muscles (RM) increase markedly during exercise in chronic heart failure (CHF). We reasoned that if the RM could subtract a fraction of the limited cardiac output (QT) from the peripheral muscles, RM unloading would improve locomotor muscle perfusion. Nine patients with CHF (left ventricle ejection fraction = 26 +/- 7%) undertook constant-work rate tests (70-80% peak) receiving proportional assisted ventilation (PAV) or sham ventilation. Relative changes (Delta%) in deoxy-hemoglobyn, oxi-Hb ([O2Hb]), tissue oxygenation index, and total Hb ([HbTOT], an index of local blood volume) in the vastus lateralis were measured by near infrared spectroscopy. In addition, QT was monitored by impedance cardiography and arterial O2 saturation by pulse oximetry (SpO2). There were significant improvements in exercise tolerance (Tlim) with PAV. Blood lactate, leg effort/Tlim and dyspnea/Tlim were lower with PAV compared with sham ventilation (P < 0.05). There were no significant effects of RM unloading on systemic O2 delivery as QT and SpO2 at submaximal exercise and at Tlim did not differ between PAV and sham ventilation (P > 0.05). Unloaded breathing, however, was related to enhanced leg muscle oxygenation and local blood volume compared with sham, i.e., higher Delta[O2Hb]% and Delta[HbTOT]%, respectively (P < 0.05). We conclude that RM unloading had beneficial effects on the oxygenation status and blood volume of the exercising muscles at similar systemic O2 delivery in patients with advanced CHF. These data suggest that blood flow was redistributed from respiratory to locomotor muscles during unloaded breathing.

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.

BackgroundRespiratory muscle unloading through proportional assist ventilation (PAV) may enhance leg oxygen delivery, thereby speeding off-exercise oxygen uptake (V.⁢O2) kinetics in patients with heart failure with reduced left ventricular ejection fraction (HFrEF).MethodsTen male patients (HFrEF = 26 ± 9%, age 50 ± 13 years, and body mass index 25 ± 3 kg m2) underwent two constant work rate tests at 80% peak of maximal cardiopulmonary exercise test to tolerance under PAV and sham ventilation. Post-exercise kinetics of V.⁢O2, vastus lateralis deoxyhemoglobin ([deoxy-Hb + Mb]) by near-infrared spectroscopy, and cardiac output (QT) by impedance cardiography were assessed.ResultsPAV prolonged exercise tolerance compared with sham (587 ± 390 s vs. 444 ± 296 s, respectively; p = 0.01). PAV significantly accelerated V.⁢O2 recovery (τ = 56 ± 22 s vs. 77 ± 42 s; p &lt; 0.05), being associated with a faster decline in Δ[deoxy-Hb + Mb] and QT compared with sham (τ = 31 ± 19 s vs. 42 ± 22 s and 39 ± 22 s vs. 78 ± 46 s, p &lt; 0.05). Faster off-exercise decrease in QT with PAV was related to longer exercise duration (r = −0.76; p &lt; 0.05).ConclusionPAV accelerates the recovery of central hemodynamics and muscle oxygenation in HFrEF. These beneficial effects might prove useful to improve the tolerance to repeated exercise during cardiac rehabilitation.