Interval exercise delays critical mechanical-ventilatory constraints with positive consequences o... more 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˙CO). Sixteen men (FEV = 42.3 ± 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˙COnadir (35 ± 3 vs. 30 ± 5) and dead space/tidal volume (0.39 ± 0.05 vs. 0.34 ± 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 ...
Background Expiratory flow limitation and lung hyperinflation promote cardiocirculatory perturbat... more 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)¼38.5612.9% predicted; PaO 2 >60 mm Hg) underwent constant work rate cycle ergometer exercise tests (70e80% peak) to the limit of tolerance (Tlim) after inhaled bronchodilators (salbutamol plus ipratropium) or placebo. Muscle (de) oxygenation (wfractional O 2 extraction) was determined in the vastus lateralis by changes (D) in the deoxyhaemoglobin/myoglobin signal ([HHb]) from nearinfrared spectroscopy, and cardiac output (QT) was monitored by impedance cardiography. Results Bronchodilators reduced lung hyperinflation and increased Tlim compared with placebo (4546131 s vs 3216140 s, respectively; p<0.05). On-exercise kinetics of QT and pulmonary O 2 uptake ð _ Vo 2 Þ were accelerated with active treatment; D[HHb] dynamics, however, were delayed by w78% and the signal amplitude diminished by w21% (p<0.01). Consequently, the ratio between _ Vo 2 and D[HHb] dynamics decreased, suggesting improved microvascular O 2 delivery (s-_ Vo 2 /MRT-D [HHb]¼4.4861.57 s vs 2.0861.15 s, p<0.05). Of note, reductions in lung hyperinflation were related to faster QT kinetics and larger decrements in s-_ Vo 2 /MRT-D[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.
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.], Jan 24, 2015
Exercise intolerance due to impaired oxidative metabolism is a prominent symptom in patients with... more Exercise intolerance due to impaired oxidative metabolism is a prominent symptom in patients with mitochondrial myopathy (MM), but it is still uncertain whether L-carnitine supplementation is beneficial for patients with MM. The aim of our study was to investigate the effects of L-carnitine on exercise performance in MM. Twelve MM subjects (mean age±SD=35.4±10.8 years) with chronic progressive external ophthalmoplegia (CPEO) were first compared to 10 healthy controls (mean age±SD=29±7.8 years) before they were randomly assigned to receive L-carnitine supplementation (3 g/daily) or placebo in a double-blind crossover design. Clinical status, body composition, respiratory function tests, peripheral muscle strength (isokinetic and isometric torque) and cardiopulmonary exercise tests (incremental to peak exercise and at 70% of maximal), constant work rate (CWR) exercise test, to the limit of tolerance [Tlim]) were assessed after 2 months of L-carnitine/placebo administration. Patients w...
Background Expiratory flow limitation and lung hyperinflation promote cardiocirculatory perturbat... more 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)¼38.5612.9% predicted; PaO 2 >60 mm Hg) underwent constant work rate cycle ergometer exercise tests (70e80% peak) to the limit of tolerance (Tlim) after inhaled bronchodilators (salbutamol plus ipratropium) or placebo. Muscle (de) oxygenation (wfractional O 2 extraction) was determined in the vastus lateralis by changes (D) in the deoxyhaemoglobin/myoglobin signal ([HHb]) from nearinfrared spectroscopy, and cardiac output (QT) was monitored by impedance cardiography. Results Bronchodilators reduced lung hyperinflation and increased Tlim compared with placebo (4546131 s vs 3216140 s, respectively; p<0.05). On-exercise kinetics of QT and pulmonary O 2 uptake ð _ Vo 2 Þ were accelerated with active treatment; D[HHb] dynamics, however, were delayed by w78% and the signal amplitude diminished by w21% (p<0.01). Consequently, the ratio between _ Vo 2 and D[HHb] dynamics decreased, suggesting improved microvascular O 2 delivery (s-_ Vo 2 /MRT-D [HHb]¼4.4861.57 s vs 2.0861.15 s, p<0.05). Of note, reductions in lung hyperinflation were related to faster QT kinetics and larger decrements in s-_ Vo 2 /MRT-D[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.
Muscle vascular dysfunction, a hallmark of chronic diseases such as heart failure and diabetes, i... more 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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.
Background: It is currently unclear whether the additive effects of a long-acting b 2-agonist (LA... more Background: It is currently unclear whether the additive effects of a long-acting b 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 Z 47.4 AE 12.9% predicted) were randomly allocated to 2-wk formoterol fumarate 12 mg twice-daily (FOR) plus TIO 18 mg 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 AE 0.42 L vs. 1.25 AE 0.39 L and 124 AE 27% vs. 68 AE 14%, respectively; p < 0.05). FOR-TIO slowed the rate of decrement in exercise IC compared to FOR-PLA (Disotime-rest Z À0.27 AE 0.40 L vs. À0.45 AE 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).
This study addressed whether O(2) delivery during recovery from high-intensity, supra-gas exchang... more 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;(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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Q&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;(T), however, declined at similar rates (τ = 64.7 ± 18.8 vs. 73.0 ± 21.6 s; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 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.
Background: Haemodynamic responses to exercise are related to physical impairment and worse progn... more 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 TM), 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 D (peak-unloaded exercise) SV <10 ml were markers of more advanced PAH (P<0.05). DCI 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 DCI 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 DCI 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 TM (PhysioFlow TM) 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.
Like other agnathans, the Pacific hagfish (Eptatretus stouti) lacks red blood cell (RBC) Cl(-)/HC... more Like other agnathans, the Pacific hagfish (Eptatretus stouti) lacks red blood cell (RBC) Cl(-)/HCO(3)(-) exchange. Despite this absence of anion exchange, the majority (86.7+/-1.4%) of the total CO(2) carried in the blood is found within the plasma as HCO(3)(-), and thus presumably is inaccessible to RBC carbonic anhydrase (CA). As such, a branchial plasma-accessible CA isozyme in hagfish would be beneficial for mobilizing the considerable plasma HCO(3)(-) stores for CO(2) excretion and blood acid-base balance. The current study used a combination of molecular and biochemical methods to identify two membrane-associated CA isozymes in the respiratory system of E. stouti. Using homology cloning methods, CA IV and XV-like isozymes were identified in the gill and RBC, respectively. Real-time PCR analysis of relative mRNA expression revealed that CA IV was specific to the gill, while CA XV was found in several tissues including the RBC, gill, liver, heart and muscle. Isolation of subcellular fractions of gill and RBC verified the presence of membrane-associated CA activity in each tissue that persisted after standard washing protocols. Unlike CA activity associated with the cytoplasmic fractions, the activity in gill membranes was not inhibited by sodium dodecyl sulphate, while RBC membrane activity was inhibited to a lesser degree than the cytoplasmic fraction. Additionally, incubation of gill membrane fractions with phosphatidylinositol-specific phospholipase C released significant CA activity into the supernatant indicating the presence of a glycophosphatidyl inositol-linkage to the membrane, as found with other CA IV and XV isozymes. These results demonstrate that Pacific hagfish possess gill and RBC plasma-accessible membrane-associated CA that may play important roles in respiratory gas exchange and acid-base balance.
BackgroundExpiratory flow limitation and lung hyperinflation promote cardiocirculatory perturbati... more BackgroundExpiratory flow limitation and lung hyperinflation promote cardiocirculatory perturbations that might impair O2 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.MethodsTwelve non- or mildly hypoxaemic males (forced expiratory volume in 1 s (FEV1)=38.5±12.9% predicted; Pao2>60
Interval exercise delays critical mechanical-ventilatory constraints with positive consequences o... more 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˙CO). Sixteen men (FEV = 42.3 ± 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˙COnadir (35 ± 3 vs. 30 ± 5) and dead space/tidal volume (0.39 ± 0.05 vs. 0.34 ± 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 ...
Background Expiratory flow limitation and lung hyperinflation promote cardiocirculatory perturbat... more 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)¼38.5612.9% predicted; PaO 2 >60 mm Hg) underwent constant work rate cycle ergometer exercise tests (70e80% peak) to the limit of tolerance (Tlim) after inhaled bronchodilators (salbutamol plus ipratropium) or placebo. Muscle (de) oxygenation (wfractional O 2 extraction) was determined in the vastus lateralis by changes (D) in the deoxyhaemoglobin/myoglobin signal ([HHb]) from nearinfrared spectroscopy, and cardiac output (QT) was monitored by impedance cardiography. Results Bronchodilators reduced lung hyperinflation and increased Tlim compared with placebo (4546131 s vs 3216140 s, respectively; p<0.05). On-exercise kinetics of QT and pulmonary O 2 uptake ð _ Vo 2 Þ were accelerated with active treatment; D[HHb] dynamics, however, were delayed by w78% and the signal amplitude diminished by w21% (p<0.01). Consequently, the ratio between _ Vo 2 and D[HHb] dynamics decreased, suggesting improved microvascular O 2 delivery (s-_ Vo 2 /MRT-D [HHb]¼4.4861.57 s vs 2.0861.15 s, p<0.05). Of note, reductions in lung hyperinflation were related to faster QT kinetics and larger decrements in s-_ Vo 2 /MRT-D[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.
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.], Jan 24, 2015
Exercise intolerance due to impaired oxidative metabolism is a prominent symptom in patients with... more Exercise intolerance due to impaired oxidative metabolism is a prominent symptom in patients with mitochondrial myopathy (MM), but it is still uncertain whether L-carnitine supplementation is beneficial for patients with MM. The aim of our study was to investigate the effects of L-carnitine on exercise performance in MM. Twelve MM subjects (mean age±SD=35.4±10.8 years) with chronic progressive external ophthalmoplegia (CPEO) were first compared to 10 healthy controls (mean age±SD=29±7.8 years) before they were randomly assigned to receive L-carnitine supplementation (3 g/daily) or placebo in a double-blind crossover design. Clinical status, body composition, respiratory function tests, peripheral muscle strength (isokinetic and isometric torque) and cardiopulmonary exercise tests (incremental to peak exercise and at 70% of maximal), constant work rate (CWR) exercise test, to the limit of tolerance [Tlim]) were assessed after 2 months of L-carnitine/placebo administration. Patients w...
Background Expiratory flow limitation and lung hyperinflation promote cardiocirculatory perturbat... more 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)¼38.5612.9% predicted; PaO 2 >60 mm Hg) underwent constant work rate cycle ergometer exercise tests (70e80% peak) to the limit of tolerance (Tlim) after inhaled bronchodilators (salbutamol plus ipratropium) or placebo. Muscle (de) oxygenation (wfractional O 2 extraction) was determined in the vastus lateralis by changes (D) in the deoxyhaemoglobin/myoglobin signal ([HHb]) from nearinfrared spectroscopy, and cardiac output (QT) was monitored by impedance cardiography. Results Bronchodilators reduced lung hyperinflation and increased Tlim compared with placebo (4546131 s vs 3216140 s, respectively; p<0.05). On-exercise kinetics of QT and pulmonary O 2 uptake ð _ Vo 2 Þ were accelerated with active treatment; D[HHb] dynamics, however, were delayed by w78% and the signal amplitude diminished by w21% (p<0.01). Consequently, the ratio between _ Vo 2 and D[HHb] dynamics decreased, suggesting improved microvascular O 2 delivery (s-_ Vo 2 /MRT-D [HHb]¼4.4861.57 s vs 2.0861.15 s, p<0.05). Of note, reductions in lung hyperinflation were related to faster QT kinetics and larger decrements in s-_ Vo 2 /MRT-D[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.
Muscle vascular dysfunction, a hallmark of chronic diseases such as heart failure and diabetes, i... more 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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.
Background: It is currently unclear whether the additive effects of a long-acting b 2-agonist (LA... more Background: It is currently unclear whether the additive effects of a long-acting b 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 Z 47.4 AE 12.9% predicted) were randomly allocated to 2-wk formoterol fumarate 12 mg twice-daily (FOR) plus TIO 18 mg 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 AE 0.42 L vs. 1.25 AE 0.39 L and 124 AE 27% vs. 68 AE 14%, respectively; p < 0.05). FOR-TIO slowed the rate of decrement in exercise IC compared to FOR-PLA (Disotime-rest Z À0.27 AE 0.40 L vs. À0.45 AE 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).
This study addressed whether O(2) delivery during recovery from high-intensity, supra-gas exchang... more 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;(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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Q&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;(T), however, declined at similar rates (τ = 64.7 ± 18.8 vs. 73.0 ± 21.6 s; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 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.
Background: Haemodynamic responses to exercise are related to physical impairment and worse progn... more 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 TM), 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 D (peak-unloaded exercise) SV <10 ml were markers of more advanced PAH (P<0.05). DCI 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 DCI 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 DCI 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 TM (PhysioFlow TM) 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.
Like other agnathans, the Pacific hagfish (Eptatretus stouti) lacks red blood cell (RBC) Cl(-)/HC... more Like other agnathans, the Pacific hagfish (Eptatretus stouti) lacks red blood cell (RBC) Cl(-)/HCO(3)(-) exchange. Despite this absence of anion exchange, the majority (86.7+/-1.4%) of the total CO(2) carried in the blood is found within the plasma as HCO(3)(-), and thus presumably is inaccessible to RBC carbonic anhydrase (CA). As such, a branchial plasma-accessible CA isozyme in hagfish would be beneficial for mobilizing the considerable plasma HCO(3)(-) stores for CO(2) excretion and blood acid-base balance. The current study used a combination of molecular and biochemical methods to identify two membrane-associated CA isozymes in the respiratory system of E. stouti. Using homology cloning methods, CA IV and XV-like isozymes were identified in the gill and RBC, respectively. Real-time PCR analysis of relative mRNA expression revealed that CA IV was specific to the gill, while CA XV was found in several tissues including the RBC, gill, liver, heart and muscle. Isolation of subcellular fractions of gill and RBC verified the presence of membrane-associated CA activity in each tissue that persisted after standard washing protocols. Unlike CA activity associated with the cytoplasmic fractions, the activity in gill membranes was not inhibited by sodium dodecyl sulphate, while RBC membrane activity was inhibited to a lesser degree than the cytoplasmic fraction. Additionally, incubation of gill membrane fractions with phosphatidylinositol-specific phospholipase C released significant CA activity into the supernatant indicating the presence of a glycophosphatidyl inositol-linkage to the membrane, as found with other CA IV and XV isozymes. These results demonstrate that Pacific hagfish possess gill and RBC plasma-accessible membrane-associated CA that may play important roles in respiratory gas exchange and acid-base balance.
BackgroundExpiratory flow limitation and lung hyperinflation promote cardiocirculatory perturbati... more BackgroundExpiratory flow limitation and lung hyperinflation promote cardiocirculatory perturbations that might impair O2 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.MethodsTwelve non- or mildly hypoxaemic males (forced expiratory volume in 1 s (FEV1)=38.5±12.9% predicted; Pao2>60
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