Maroula Vasilopoulou

HUMAN RESPIRATORY MUSCLE BLOOD FLOW MEASURED BY NEAR-INFRARED SPECTROSCOPY AND INDOCYANINE GREEN

Measurement of respiratory muscle blood flow (RMBF) in humans has important implications for understanding patterns of blood flow distribution during exercise in healthy individuals and those with chronic disease. Previous studies examining RMBF in humans have required invasive methods on anesthetized subjects. To assess RMBF in awake subjects, we applied an indicator-dilution method using near-infrared spectroscopy (NIRS) and the light-absorbing tracer indocyanine green dye (ICG). NIRS optodes were placed on the left seventh intercostal space at the apposition of the costal diaphragm and on an inactive control muscle (vastus lateralis). The primary respiratory muscles within view of the NIRS optodes include the internal and external intercostals. Intravenous bolus injection of ICG allowed for cardiac output (by the conventional dye-dilution method with arterial sampling), RMBF, and vastus lateralis blood flow to be quantified simultaneously. Esophageal and gastric pressures were also measured to calculate the work of breathing and transdiaphragmatic pressure. Measurements were obtained in five conscious humans during both resting breathing and three separate 5-min bouts of constant isocapnic hyperpnea at 27.1 +/- 3.2, 56.0 +/- 6.1, and 75.9 +/- 5.7% of maximum minute ventilation as determined on a previous maximal exercise test. RMBF progressively increased (9.9 +/- 0.6, 14.8 +/- 2.7, 29.9 +/- 5.8, and 50.1 +/- 12.5 ml 100 ml(-1) min(-1), respectively) with increasing levels of ventilation while blood flow to the inactive control muscle remained constant (10.4 +/- 1.4, 8.7 +/- 0.7, 12.9 +/- 1.7, and 12.2 +/- 1.8 ml 100 ml(-1) min(-1), respectively). As ventilation rose, RMBF was closely and significantly correlated with 1) cardiac output (r = 0.994, P = 0.006), 2) the work of breathing (r = 0.995, P = 0.005), and 3) transdiaphragmatic pressure (r = 0.998, P = 0.002). These data suggest that the NIRS-ICG technique provides a feasible and sensitive index of RMBF at different levels of ventilation in humans.

Contribution of respiratory muscle blood flow to exercise‐induced diaphragmatic fatigue in trained cyclists

We investigated whether the greater degree of exercise‐induced diaphragmatic fatigue previously reported in highly trained athletes in hypoxia (compared with normoxia) could have a contribution from limited respiratory muscle blood flow. Seven trained cyclists completed three constant load 5 min exercise tests at inspired O2 fractions () of 0.13, 0.21 and 1.00 in balanced order. Work rates were selected to produce the same tidal volume, breathing frequency and respiratory muscle load at each (63 ± 1, 78 ± 1 and 87 ± 1% of normoxic maximal work rate, respectively). Intercostals and quadriceps muscle blood flow (IMBF and QMBF, respectively) were measured by near‐infrared spectroscopy over the left 7th intercostal space and the left vastus lateralis muscle, respectively, using indocyanine green dye. The mean pressure time product of the diaphragm and the work of breathing did not differ across the three exercise tests. After hypoxic exercise, twitch transdiaphragmatic pressure fell by 33.3 ± 4.8%, significantly (P < 0.05) more than after both normoxic (25.6 ± 3.5% reduction) and hyperoxic (26.6 ± 3.3% reduction) exercise, confirming greater fatigue in hypoxia. Despite lower leg power output in hypoxia, neither cardiac output nor QMBF (27.6 ± 1.2 l min−1 and 100.4 ± 8.7 ml (100 ml)−1 min−1, respectively) were significantly different compared with normoxia (28.4 ± 1.9 l min−1 and 94.4 ± 5.2 ml (100 ml)−1 min−1, respectively) and hyperoxia (27.8 ± 1.6 l min−1 and 95.1 ± 7.8 ml (100 ml)−1 min−1, respectively). Neither IMBF was different across hypoxia, normoxia and hyperoxia (53.6 ± 8.5, 49.9 ± 5.9 and 52.9 ± 5.9 ml (100 ml)−1 min−1, respectively). We conclude that when respiratory muscle energy requirement is not different between normoxia and hypoxia, diaphragmatic fatigue is greater in hypoxia as intercostal muscle blood flow is not increased (compared with normoxia) to compensate for the reduction in , thus further compromising O2 supply to the respiratory muscles.

Heliox increases quadriceps muscle oxygen delivery during exercise in COPD patients with and without dynamic hyperinflation

Some reports suggest that heliox breathing during exercise may improve peripheral muscle oxygen availability in patients with chronic obstructive pulmonary disease (COPD). Besides COPD patients who dynamically hyperinflate during exercise (hyperinflators), there are patients who do not hyperinflate (non-hyperinflators). As heliox breathing may differently affect cardiac output in hyperinflators (by increasing preload and decreasing afterload of both ventricles) and non-hyperinflators (by increasing venous return) during exercise, it was reasoned that heliox administration would improve peripheral muscle oxygen delivery possibly by different mechanisms in those two COPD categories. Chest wall volume and respiratory muscle activity were determined during constant-load exercise at 75% peak capacity to exhaustion, while breathing room air or normoxic heliox in 17 COPD patients: 9 hyperinflators (forced expiratory volume in 1 s = 39 ± 5% predicted), and 8 non-hyperinflators (forced expiratory volume in 1 s = 48 ± 5% predicted). Quadriceps muscle blood flow was measured by near-infrared spectroscopy using indocyanine green dye. Hyperinflators and non-hyperinflators demonstrated comparable improvements in endurance time during heliox (231 ± 23 and 257 ± 28 s, respectively). At exhaustion in room air, expiratory muscle activity (expressed by peak-expiratory gastric pressure) was lower in hyperinflators than in non-hyperinflators. In hyperinflators, heliox reduced end-expiratory chest wall volume and diaphragmatic activity, and increased arterial oxygen content (by 17.8 ± 2.5 ml/l), whereas, in non-hyperinflators, heliox reduced peak-expiratory gastric pressure and increased systemic vascular conductance (by 11.0 ± 2.8 ml·min(-1)·mmHg(-1)). Quadriceps muscle blood flow and oxygen delivery significantly improved during heliox compared with room air by a comparable magnitude (in hyperinflators by 6.1 ± 1.3 ml·min(-1)·100 g(-1) and 1.3 ± 0.3 ml O(2)·min(-1)·100 g(-1), and in non-hyperinflators by 7.2 ± 1.6 ml·min(-1)·100 g(-1) and 1.6 ± 0.3 ml O(2)·min(-1)·100 g(-1), respectively). Despite similar increase in locomotor muscle oxygen delivery with heliox in both groups, the mechanisms of such improvements were different: 1) in hyperinflators, heliox increased arterial oxygen content and quadriceps blood flow at similar cardiac output, whereas 2) in non-hyperinflators, heliox improved central hemodynamics and increased systemic vascular conductance and quadriceps blood flow at similar arterial oxygen content.

Intensity of daily physical activity is associated with central hemodynamic and leg muscle oxygen availability in COPD

In chronic obstructive pulmonary disease (COPD), daily physical activity is reported to be adversely associated with the magnitude of exercise-induced dynamic hyperinflation and peripheral muscle weakness. There is limited evidence whether central hemodynamic, oxygen transport, and peripheral muscle oxygenation capacities also contribute to reduced daily physical activity. Nineteen patients with COPD (FEV1, 48 ± 14% predicted) underwent a treadmill walking test at a speed corresponding to the individual patients mean walking intensity, captured by a triaxial accelerometer during a preceding 7-day period. During the indoor treadmill test, the individual patient mean walking intensity (range, 1.5 to 2.3 m/s2) was significantly correlated with changes from baseline in cardiac output recorded by impedance cardiography (range, 1.2 to 4.2 L/min; r = 0.73), systemic vascular conductance (range, 7.9 to 33.7 ml·min(-1)·mmHg(-1); r = 0.77), systemic oxygen delivery estimated from cardiac output and arterial pulse-oxymetry saturation (range, 0.15 to 0.99 L/min; r = 0.70), arterio-venous oxygen content difference calculated from oxygen uptake and cardiac output (range, 3.7 to 11.8 mlO2/100 ml; r = -0.73), and quadriceps muscle fractional oxygen saturation assessed by near-infrared spectrometry (range, -6 to 23%; r = 0.77). In addition, mean walking intensity significantly correlated with the quadriceps muscle force adjusted for body weight (range, 0.28 to 0.60; r = 0.74) and the ratio of minute ventilation over maximal voluntary ventilation (range, 38 to 89%, r = -0.58). In COPD, in addition to ventilatory limitations and peripheral muscle weakness, intensity of daily physical activity is associated with both central hemodynamic and peripheral muscle oxygenation capacities regulating the adequacy of matching peripheral muscle oxygen availability by systemic oxygen transport.

Home-based maintenance tele-rehabilitation reduces the risk for acute exacerbations of COPD, hospitalisations and emergency department visits

Pulmonary rehabilitation (PR) remains grossly underutilised by suitable patients worldwide. We investigated whether home-based maintenance tele-rehabilitation will be as effective as hospital-based maintenance rehabilitation and superior to usual care in reducing the risk for acute chronic obstructive pulmonary disease (COPD) exacerbations, hospitalisations and emergency department (ED) visits. Following completion of an initial 2-month PR programme this prospective, randomised controlled trial (between December 2013 and July 2015) compared 12 months of home-based maintenance tele-rehabilitation (n=47) with 12 months of hospital-based, outpatient, maintenance rehabilitation (n=50) and also to 12 months of usual care treatment (n=50) without initial PR. In a multivariate analysis during the 12-month follow-up, both home-based tele-rehabilitation and hospital-based PR remained independent predictors of a lower risk for 1) acute COPD exacerbation (incidence rate ratio (IRR) 0.517, 95% CI 0.389–0.687, and IRR 0.635, 95% CI 0.473–0.853), respectively, and 2) hospitalisations for acute COPD exacerbation (IRR 0.189, 95% CI 0.100–0.358, and IRR 0.375, 95% CI 0.207–0.681), respectively. However, only home-based maintenance tele-rehabilitation and not hospital-based, outpatient, maintenance PR was an independent predictor of ED visits (IRR 0.116, 95% CI 0.072–0.185). Home-based maintenance tele-rehabilitation is equally effective as hospital-based, outpatient, maintenance PR in reducing the risk for acute COPD exacerbation and hospitalisations. In addition, it encounters a lower risk for ED visits, thereby constituting a potentially effective alternative strategy to hospital-based, outpatient, maintenance PR. Home tele-rehabilitation reduces risk of COPD exacerbation; is effective alternative to in-hospital rehabilitation http://ow.ly/T17g30ap9cY

On- and off-exercise kinetics of cardiac output in response to cycling and walking in COPD patients with GOLD Stages I-IV.

Exercise-induced dynamic hyperinflation and large intrathoracic pressure swings may compromise the normal increase in cardiac output (Q) in Chronic Obstructive Pulmonary Disease (COPD). Therefore, it is anticipated that the greater the disease severity, the greater would be the impairment in cardiac output during exercise. Eighty COPD patients (20 at each GOLD Stage) and 10 healthy age-matched individuals undertook a constant-load test on a cycle-ergometer (75% WR(peak)) and a 6min walking test (6MWT). Cardiac output was measured by bioimpedance (PhysioFlow, Enduro) to determine the mean response time at the onset of exercise (MRTon) and during recovery (MRToff). Whilst cardiac output mean response time was not different between the two exercise protocols, MRT responses during cycling were slower in GOLD Stages III and IV compared to Stages I and II (MRTon: Stage I: 45±2, Stage II: 65±3, Stage III: 90±3, Stage IV: 106±3s; MRToff: Stage I: 42±2, Stage II: 68±3, Stage III: 87±3, Stage IV: 104±3s, respectively). In conclusion, the more advanced the disease severity the more impaired is the hemodynamic response to constant-load exercise and the 6MWT, possibly reflecting greater cardiovascular impairment and/or greater physical deconditioning.

Limitation in tidal volume expansion partially determines the intensity of physical activity in COPD

In patients with chronic obstructive pulmonary disease (COPD), reduced levels of daily physical activity are associated with the degree of impairment in lung, peripheral muscle, and central hemodynamic function. There is, however, limited evidence as to whether limitations in tidal volume expansion also, importantly, determine daily physical activity levels in COPD. Eighteen consecutive patients with COPD [9 active (forced expiratory volume in 1 s, FEV1: 1.59 ± 0.64 l) with an average daily movement intensity >1.88 m/s(2) and 9 less active patients (FEV1: 1.16 ± 0.41 l) with an average intensity <1.88 m/s(2)] underwent a 4-min treadmill test at a constant speed corresponding to each individual patients average movement intensity, captured by a triaxial accelerometer during a preceding 7-day period. When chest wall volumes, captured by optoelectronic plethysmography, were expressed relative to comparable levels of minute ventilation (ranging between 14.5 ± 4.3 to 33.5 ± 4.4 l/min), active patients differed from the less active ones in terms of the lower increase in end-expiratory chest wall volume (by 0.15 ± 0.17 vs. 0.45 ± 0.21 l), the greater expansion in tidal volume (by 1.76 ± 0.58 vs. 1.36 ± 0.24 l), and the larger inspiratory reserve chest wall volume (IRVcw: by 0.81 ± 0.25 vs. 0.39 ± 0.27 l). IRVcw (r(2) = 0.420), expiratory flow (r(2) change = 0.174), and Borg dyspnea score (r(2) change = 0.123) emerged as the best contributors, accounting for 71.7% of the explained variance in daily movement intensity. Patients with COPD exhibiting greater ability to expand tidal volume and to maintain adequate inspiratory reserve volume tend to be more physically active. Thus interventions aiming at mitigating restrictions on operational chest wall volumes are expected to enhance daily physical activity levels in COPD.

Quadriceps muscle blood flow and oxygen availability during repetitive bouts of isometric exercise in simulated sailing

Abstract In this study, we wished to determine whether the observed reduction in quadriceps muscle oxygen availability, reported during repetitive bouts of isometric exercise in simulated sailing efforts (i.e. hiking), is because of restricted muscle blood flow. Six national-squad Laser sailors initially performed three successive 3-min hiking bouts followed by three successive 3-min cycling tests sustained at constant intensities reproducing the cardiac output recorded during each of the three hiking bouts. The blood flow index (BFI) was determined from assessment of the vastus lateralis using near-infrared spectroscopy in association with the light-absorbing tracer indocyanine green dye, while cardiac output was determined from impedance cardiography. At equivalent cardiac outputs (ranging from 10.3±0.5 to 14.8±0.86 L · min−1), the increase from baseline in vastus lateralis BFI across the three hiking bouts (from 1.1±0.2 to 3.1±0.6 nM · s−1) was lower (P = 0.036) than that seen during the three cycling bouts (from 1.1±0.2 to 7.2±1.4 nM · s−1) (Cohens d: 3.80 nM · s−1), whereas the increase from baseline in deoxygenated haemoglobin (by ∼17.0±2.9 μM) (an index of tissue oxygen extraction) was greater (P = 0.006) during hiking than cycling (by ∼5.3±2.7 μM) (Cohens d: 4.17 μM). The results suggest that reduced vastus lateralis muscle oxygen availability during hiking arises from restricted muscle blood flow in the isometrically acting quadriceps muscles.

Activity monitoring reflects cardiovascular and metabolic variations in COPD patients across GOLD stages II to IV.

We investigated whether activity monitoring reliably reflects variations in oxygen transport and utilization during walking in COPD patients. Forty-two patients (14 in each GOLD stage II, III and IV) performed an incremental treadmill protocol to the limit of tolerance. Breath-by-breath gas exchange, central hemodynamic variables and activity monitoring were simultaneously recorded. Physiological variables and accelerometer outputs rose linearly with walking speeds. Strong correlations (r[interquartile range, IQR]) were found between treadmill walking intensity (WI: range 0.8-2.0 ms(-2)) and oxygen consumption (0.95 [IQR 0.87-0.97]), (range 7.6-15.5 ml kg(-1)min(-1)); minute ventilation (0.95 [IQR 0.86-0.98]), (range 20-37 l min(-1)); cardiac output (0.89 [IQR 0.73-0.94]), (range 6.8-11.5 l min(-1)) and arteriovenous oxygen concentration difference (0.84 [IQR 0.76-0.90]), (range 7.7-12.1 ml O2100 ml(-1)). Correlations between WI and gas exchange or central hemodynamic parameters were not different across GOLD stages. In conclusion, central hemodynamic, respiratory and muscle metabolic variations during incremental treadmill exercise are tightly associated to changes in walking intensity as recorded by accelerometry across GOLD stages II to IV. Interestingly, the magnitude of these associations is not different across GOLD stages.

Interval training induces clinically meaningful effects in daily activity levels in COPD

Mounting evidence suggests that daily activity levels (DAL) in patients with chronic obstructive pulmonary disease (COPD) are markedly low compared with healthy age-matched individuals and are associated with poorer health status and prognosis [1]. COPD severity negatively impacts on DAL since patients with low DAL experience greater ventilatory, central haemodynamic and peripheral muscle oxygenation constraints during activities of daily living when compared with more physically active counterparts [2, 3]. Although exercise training as part of pulmonary rehabilitation has shown to mitigate the aforementioned physiological constraints [4], there is no evidence of clinically meaningful improvements in DAL following pulmonary rehabilitation [5] as manifested by a mean increase of at least 1000 steps·day−1 [6]. This has been attributed to methodological shortfalls, such as lack of adequately controlled studies, small sample size, short duration of pulmonary rehabilitation programmes, application of activity monitors non-validated for COPD patients [5] and insufficient exercise intensities to induce true physiological training effects. Interval exercise training has been shown to allow application of intense loads to peripheral muscles that induce substantial physiological effects manifested by mitigation of respiratory and central haemodynamic limitations and partial restoration of peripheral muscle dysfunction in patients with diverse COPD severity [7, 8]. In this context, it is reasoned that application of this training modality would allow transfer of the aforementioned physiological benefits into clinically meaningful improvements in DAL [2, 3]. Accordingly, the purpose of this randomised controlled study was to investigate the effect of a 12-week high-intensity interval exercise training programme in DAL in addition to usual care in patients with COPD. 12 weeks of interval training induces clinically meaningful effects in amount and intensity of daily activities in COPD http://ow.ly/rZXI3002awp