Excess ventilation in COPD: Implications for dyspnoea and tolerance to interval exercise.

Interval exercise delays critical mechanical-ventilatory constraints with positive consequences on Dyspnoea and exercise tolerance in COPD. We hypothesized that those advantages of interval exercise would be partially off-set in patients showing excessive ventilation (V˙E) to metabolic demand (V˙CO2). Sixteen men (FEV1 = 42.3 ±â€¯8.9%) performed, on different days, 30 s and 60 s bouts at 100% peak (on) interspersed by moderate exercise at 40% (off). Nine patients did not sustain exercise for 30 min irrespective of on duration. They presented with higher V˙E/V˙CO2 nadir (35 ±â€¯3 vs. 30 ±â€¯5) and dead space/tidal volume (0.39 ±â€¯0.05 vs. 0.34 ±â€¯0.06) compared to their counterparts (p < 0.05). [Lactate], operating lung volumes and symptom burden (dyspnoea and leg effort) were also higher (p < 0.05). Unloading off decreased the metabolic-ventilatory demands, thereby allowing 7/9 patients to exercise for 30 min. Increased wasted ventilation accelerates the rate at which critical mechanical constraints and limiting dyspnoea are reached during interval exercise in patients with COPD.

Signal-morphology impedance cardiography during incremental cardiopulmonary exercise testing in pulmonary arterial hypertension.

BACKGROUND: Haemodynamic responses to exercise are related to physical impairment and worse prognosis in patients with pulmonary arterial hypertension (PAH). It is clinically relevant, therefore, to investigate the practical usefulness of non-invasive methods of monitoring exercise haemodynamics in this patient population. METHODS: Using a novel impedance cardiography (ICG) approach that does not require basal impedance estimations and relies on a morphological analysis of the impedance signal (Signal-Morphology-ICG(™)), stroke volume (SV) and cardiac index (CI) were evaluated in 50 patients and 21 age-matched controls during a ramp-incremental cardiopulmonary exercise testing. RESULTS: Technically unacceptable readings were found in 12 of 50 (24%) patients. In the remaining subjects, early decrease (N = 9) or a 'plateau' in SV (N = 8) and Δ (peak-unloaded exercise) SV <10 ml were markers of more advanced PAH (P<0.05). ΔCI ≤ 1.5-fold and early estimated lactate threshold were the only independent predictors of a severely reduced peak oxygen uptake (VO(2)) in patients (R(2) = 0.71, P<0.001). The finding of ΔCI ≤ 1.5-fold plus peak VO(2) < 50% predicted was associated with a number of clinical and functional markers of disease severity (P<0.001). In addition, abnormal SV responses and ΔCI ≤ 1.5-fold were significantly related to 1-year frequency of PAH-related adverse events (death and balloon atrial septostomy, N = 8; P<0.05). CONCLUSIONS: 'Qualitative' and 'semi-quantitative' signal-morphology impedance cardiography(™) (PhysioFlow(™)) during incremental exercise provided clinically useful information to estimate disease severity and short-term prognosis in patients with PAH in whom acceptable impedance signals could be obtained.

Skeletal muscle reoxygenation after high-intensity exercise in mitochondrial myopathy.

This study addressed whether O(2) delivery during recovery from high-intensity, supra-gas exchange threshold exercise would be matched to O(2) utilization at the microvascular level in patients with mitochondrial myopathy (MM). Off-exercise kinetics of (1) pulmonary O(2) uptake VO(2P) (2) an index of fractional O(2) extraction by near-infrared spectroscopy (Δ[deoxy-Hb + Mb]) in the vastus lateralis and (3) cardiac output (Q'(T)) by impedance cardiography were assessed in 12 patients with biopsy-proven MM (chronic progressive external ophthalmoplegia) and 12 age- and gender-matched controls. Kinetics of VO(2P) were significantly slower in patients than controls (τ = 53.8 ± 16.5 vs. 38.8 ± 7.6 s, respectively; p < 0.05). Q'(T), however, declined at similar rates (τ = 64.7 ± 18.8 vs. 73.0 ± 21.6 s; p > 0.05) being typically slower than [Formula: see text] in both groups. Importantly, Δ[deoxy-Hb + Mb] dynamics (MRT) were equal to, or faster than, τVO(2P) in patients and controls, respectively. In fact, there were no between-group differences in τVO(2P)MRTΔ[deoxy-Hb + Mb] (1.1 ± 0.4 vs. 1.0 ± 0.2, p > 0.05) thereby indicating similar rates of microvascular O(2) delivery. These data indicate that the slower rate of recovery of muscle metabolism after high-intensity exercise is not related to impaired microvascular O(2) delivery in patients with MM. This phenomenon, therefore, seems to reflect the intra-myocyte abnormalities that characterize this patient population.

Bronchodilators accelerate the dynamics of muscle O2 delivery and utilisation during exercise in COPD.

BACKGROUND: Expiratory flow limitation and lung hyperinflation promote cardiocirculatory perturbations that might impair O(2) delivery to locomotor muscles in patients with chronic obstructive pulmonary disease (COPD). The hypothesis that decreases in lung hyperinflation after the inhalation of bronchodilators would improve skeletal muscle oxygenation during exercise was tested. METHODS: Twelve non- or mildly hypoxaemic males (forced expiratory volume in 1 s (FEV(1))=38.5+/-12.9% predicted; Pao(2)>60 mm Hg) underwent constant work rate cycle ergometer exercise tests (70-80% peak) to the limit of tolerance (Tlim) after inhaled bronchodilators (salbutamol plus ipratropium) or placebo. Muscle (de)oxygenation (approximately fractional O(2) extraction) was determined in the vastus lateralis by changes (Delta) in the deoxyhaemoglobin/myoglobin signal ([HHb]) from near-infrared spectroscopy, and cardiac output (QT) was monitored by impedance cardiography. RESULTS: Bronchodilators reduced lung hyperinflation and increased Tlim compared with placebo (454+/-131 s vs 321+/-140 s, respectively; p<0.05). On-exercise kinetics of QT and pulmonary O(2) uptake V(o(2))were accelerated with active treatment; Delta[HHb] dynamics, however, were delayed by approximately 78% and the signal amplitude diminished by approximately 21% (p<0.01). Consequently, the ratio between V(o(2)) and Delta[HHb] dynamics decreased, suggesting improved microvascular O(2) delivery (tau-V(o(2))/MRT-Delta[HHb]=4.48+/-1.57 s vs 2.08+/-1.15 s, p<0.05). Of note, reductions in lung hyperinflation were related to faster QT kinetics and larger decrements in tau-V(o(2))/MRT-Delta[HHb] (p<0.01). CONCLUSIONS: Decreases in operating lung volumes after the inhalation of bronchodilators are associated with faster 'central' cardiovascular adjustments to high-intensity exercise with beneficial consequences on muscle oxygenation in patients with moderate to severe COPD.

Kinetics analysis of muscle arterial-venous O(2) difference profile during exercise.

Muscle vascular dysfunction, a hallmark of chronic diseases such as heart failure and diabetes, impairs the matching of blood flow (Q(m)) to O(2) utilization (V(O(2m))) following exercise onset. One recently described consequence of this behavior is that arterial-venous O(2) difference [(a-v)(O(2)), the mirror image of muscle vascular oxygenation] transiently overshoots the subsequent steady-state and, in so doing, may provide important information regarding Q(m) versus V(O(2m)) dynamics. Using computer simulations, we tested the hypothesis that key parameters of the (a-v)(O(2)) overshoot - peak response, downward time constant (tau(D)), and total area - would relate quantitatively to Q(m) kinetics. Our results demonstrated significant proportionality (all p<0.01) between Q(m) mean response time and peak (r(2)=0.56), tau(D) (r(2)=72) and total area (r(2)=0.97) of (a-v)(O(2)) overshoot. These results suggest that analysis of (a-v)(O(2)) or its proxy, muscle vascular oxygenation [measured using near-infrared spectroscopy or phosphorescence quenching], provides valuable information regarding blood flow and vascular function particularly in reference to V(O(2m)) kinetics.

Effects of tiotropium and formoterol on dynamic hyperinflation and exercise endurance in COPD.

BACKGROUND: It is currently unclear whether the additive effects of a long-acting beta(2)-agonist (LABA) and the antimuscarinic tiotropium bromide (TIO) on resting lung function are translated into lower operating lung volumes and improved exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). METHODS: On a double-blind and cross-over study, 33 patients (FEV(1) = 47.4 +/- 12.9% predicted) were randomly allocated to 2-wk formoterol fumarate 12 microg twice-daily (FOR) plus TIO 18 microg once-daily or FOR plus placebo (PLA). Inspiratory capacity (IC) was obtained on constant-speed treadmill tests to the limit of tolerance (Tlim). RESULTS: FOR-TIO was superior to FOR-PLA in increasing post-treatment FEV(1) and Tlim (1.34 +/- 0.42 L vs. 1.25 +/- 0.39 L and 124 +/- 27% vs. 68 +/- 14%, respectively; p < 0.05). FOR-TIO slowed the rate of decrement in exercise IC compared to FOR-PLA (Deltaisotime-rest = -0.27 +/- 0.40 L vs. -0.45 +/- 0.36 L, p < 0.05). In addition, end-expiratory lung volume (% total lung capacity) was further reduced with FOR-TIO (p < 0.05). Of note, patients showing greater increases in Tlim with FOR-TIO (16/26, 61.6%) had more severe airways obstruction and lower exercise capacity at baseline. Improvement in Tlim with FOR-TIO was also related to larger increases in FEV(1) (p < 0.05). CONCLUSIONS: Compared to FOR monotherapy, FOR-TIO further improved effort-induced dynamic hyperinflation and exercise endurance in patients with moderate-to-severe COPD. These beneficial consequences were more likely to be found in severely-disabled patients with larger resting functional responses to the combination therapy. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00680056 [ClinicalTrials.gov].

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.