Effect of increased inspiratory muscle work on blood flow to inactive and active limbs during submaximal dynamic exercise.

NEW FINDINGS: What is the central question of this study? Increased respiratory muscle activation is associated with neural and cardiovascular consequences via the respiratory muscle metaboreflex. Does increased sympathetic vasoconstriction originating from the respiratory musculature elicit a reduction in blood flow to an inactive limb in order to maintain blood flow to an active limb? What is the main finding and its importance? Arm blood flow was reduced whereas leg blood flow was preserved during mild leg exercise with inspiratory resistance. Blood flow to the active limb is maintained via sympathetic control of blood flow redistribution when the respiratory muscle-induced metaboreflex is activated. ABSTRACT: The purpose of this study was to elucidate the effect of increasing inspiratory muscle work on blood flow to inactive and active limbs. Healthy young men (n = 10, 20 ± 2 years of age) performed two bilateral dynamic knee-extension and knee-flexion exercise tests at 40% peak oxygen uptake for 10 min. The trials consisted of spontaneous breathing for 5 min followed by voluntary hyperventilation either with or without inspiratory resistance for 5 min (40% of maximal inspiratory mouth pressure, inspiratory duty cycle of 50% and a breathing frequency of 40 breaths min-1 ). Mean arterial blood pressure was acquired using finger photoplethysmography. Blood flow in the brachial artery (inactive limb) and in the femoral artery (active limb) were monitored using Doppler ultrasound. Mean arterial blood pressure during exercise was higher (P < 0.05) with inspiratory resistance (121 ± 7 mmHg) than without resistance (99 ± 5 mmHg). Brachial artery blood flow increased during exercise without inspiratory resistance (120 ± 31 ml min-1 ) compared with the resting level, whereas it was attenuated with inspiratory resistance (65 ± 43 ml min-1 ). Femoral artery blood flow increased at the onset of exercise and was maintained throughout exercise without inspiratory resistance (2576 ± 640 ml min-1 ) and was unchanged when inspiratory resistance was added (2634 ± 659 ml min-1 ; P > 0.05). These results suggest that sympathetic control of blood redistribution to active limbs is facilitated, in part, by the respiratory muscle-induced metaboreflex.

Inspiratory muscle training abolishes the blood lactate increase associated with volitional hyperpnoea superimposed on exercise and accelerates lactate and oxygen uptake kinetics at the onset of exercise.

We examined the effects of inspiratory muscle training (IMT) upon volitional hyperpnoea-mediated increases in blood lactate ([lac(-)](B)) during cycling at maximal lactate steady state (MLSS) power, and blood lactate and oxygen uptake kinetics at the onset of exercise. Twenty males formed either an IMT (n = 10) or control group (n = 10). Prior to and following a 6-week intervention, two 30 min trials were performed at MLSS (207 ± 28 W), determined using repeated 30 min constant power trials. The first was a reference trial, whereas during the second trial, from 20 to 28 min, participants mimicked the breathing pattern commensurate with 90% of the maximal incremental exercise test minute ventilation ([Formula: see text]). Prior to the intervention, the MLSS [lac(-)](B) was 3.7 ± 1.8 and 3.9 ± 1.6 mmol L(-1) in the IMT and control groups, respectively. During volitional hyperpnoea, [Formula: see text] increased from 79.9 ± 9.5 and 76.3 ± 15.4 L min(-1) at 20 min to 137.8 ± 15.2 and 135.0 ± 19.7 L min(-1) in IMT and control groups, respectively; [lac(-)](B) concurrently increased by 1.0 ± 0.6 (+27%) and 0.9 ± 0.7 mmol L(-1) (+25%), respectively (P < 0.05). Following the intervention, maximal inspiratory mouth pressure increased 19% in the IMT group only (P < 0.01). Following IMT only, the increase in [lac(-)](B) during volitional hyperpnoea was abolished (P < 0.05). In addition, the blood lactate (-28%) and phase II oxygen uptake (-31%) kinetics time constants at the onset of exercise and the MLSS [lac(-)](B) (-15%) were reduced (P < 0.05). We attribute these changes to an IMT-mediated increase in the oxidative and/or lactate transport capacity of the inspiratory muscles.

Prefrontal cortex activation during incremental inspiratory loading in healthy participants.

We aimed to investigate whether changes in prefrontal cortex (PFC) oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb) associates with inspiratory muscle effort during inspiratory threshold loading (ITL) in healthy participants. Participants performed an incremental ITL. Breathing pattern, partial pressure of end-tidal CO2 (PETCO2), mouth pressure and O2Hb and HHb over the right dorsolateral PFC, sternocleidomastoid (SCM), and diaphragm/intercostals (Dia/IC) were monitored. Fourteen healthy participants (8 men; 29 ± 5 years) completed testing. Dyspnea was higher post- than pre-ITL (5 ± 1 vs. 0 ± 1, respectively; P<0.05). PFC O2Hb increased (P < 0.001) and HHb decreased (P = 0.001) at low loads but remained stable with increasing ITL intensities. PFC total hemoglobin increased at task failure compared to rest. SCM HHb increased throughout increasing intensities. SCM and Dia/IC total hemoglobin increased in the at task failure compared to rest. PETCO2 did not change (P = 0.528). PFC is activated early during the ITL but does not show central fatigue at task failure despite greater dyspnea and an imbalance of SCM oxygen demand and delivery.

Inspiratory flow-resistive breathing, respiratory muscle-induced systemic oxidative stress, and diaphragm fatigue in healthy humans.

We questioned whether the respiratory muscles of humans contribute to systemic oxidative stress following inspiratory flow-resistive breathing, whether the amount of oxidative stress is influenced by the level of resistive load, and whether the amount of oxidative stress is related to the degree of diaphragm fatigue incurred. Eight young and healthy participants attended the laboratory for four visits on separate days. During the first visit, height, body mass, lung function, and maximal inspiratory mouth and transdiaphragmatic pressure (Pdimax) were assessed. During visits 2-4, participants undertook inspiratory flow-resistive breathing with either no resistance (control) or resistive loads equivalent to 50 and 70% of their Pdimax (Pdimax50% and Pdimax70%) for 30 min. Participants undertook one resistive load per visit, and the order in which they undertook the loads was randomized. Inspiratory muscle pressures were higher (P < 0.05) during the 5th and Final min of Pdimax50% and Pdimax70% compared with control. Plasma F2-isoprostanes increased (P < 0.05) following inspiratory flow-resistive breathing at Pdimax70%. There were no increases in plasma protein carbonyls or total antioxidant capacity. Furthermore, although we evidenced small reductions in transdiapragmaic twitch pressures (PdiTW) after inspiratory flow-resistive breathing at Pdimax50% and Pdimax70%, this was not related to the increase in plasma F2-isoprostanes. Our novel data suggest that it is only when sufficiently strenuous that inspiratory flow-resistive breathing in humans elicits systemic oxidative stress evidenced by elevated plasma F2-isoprostanes, and based on our data, this is not related to a reduction in PdiTW.NEW & NOTEWORTHY We examined whether the respiratory muscles of humans contribute to systemic oxidative stress following inspiratory flow-resistive breathing, whether the amount of oxidative stress is influenced by the level of resistive load, and whether the amount of oxidative stress is related to the degree of diaphragm fatigue incurred. It is only when sufficiently strenuous that inspiratory flow-resistive breathing elevates plasma F2-isoprostanes, and our novel data show that this is not related to a reduction in transdiaphragmatic twitch pressure.

Preliminary study: comparative effects of lung volume therapy between slow and fast deep-breathing techniques on pulmonary function, respiratory muscle strength, oxidative stress, cytokines, 6-minute walking distance, and quality of life in persons with COPD.

BACKGROUND: Lung volume therapy with the Voldyne® device can improve lung volume and has a nonsignificant benefit on respiratory muscle strength via the slow deep-breathing technique (SDBT); whereas respiratory muscle training with a respiratory muscle trainer via the fast deep-breathing technique (FDBT) has produced a significant improvement in people with COPD. Thus, the aim of this study was to compare the efficiency of lung volume therapy with the Voldyne® device with the SDBT and FDBT on pulmonary function, respiratory muscle strength, oxidative stress, cytokines, walking capacity, and quality of life (QoL) in people with COPD. METHODS: A total of 30 COPD patient volunteers with mild (stage I) to moderate (stage II) severity were randomized into two groups: SDBT (n=15) and FDBT (n=15). Pulmonary function (FVC, FEV1, and FEV1/FVC), maximal inspiratory mouth pressure (PImax), oxidative stress status (total antioxidant capacity [TAC], glutathione [GSH], malondialdehyde [MDA], and nitric oxide [NO]), inflammatory cytokines (tumor necrosis factor-alpha [TNF-α] and IL-6), 6-minute walking distance (6MWD), and total clinical COPD questionnaire (CCQ) score were evaluated before and after 4 weeks of training. RESULTS: All the parameters had no statistical difference between the groups before training. The PImax, TAC, IL-6, total QoL score, and 6MWD changed significantly in the SDBT group after the 4-week experiment as compared to those in the pre-experimental period, whereas FVC, FEV1, FEV1%, FEV1/FVC%, PImax, TAC, MDA, NO, TNF-α, IL-6, 6MWD, and total CCQ score changed significantly in the FDBT group as compared to those in the pre-experimental period. The FEV1%, PImax, TNF-α, IL-6, and total CCQ score differed significantly in the FDBT group in the post-experimental period as compared to those in the SDBT group. CONCLUSION: This preliminary study concluded that the application of incentive spirometry with the Voldyne® device via fast deep breathing possibly improved respiratory muscle strength and QoL and reduced inflammatory cytokines, MDA, and NO better than that via slow deep breathing among people with COPD.

Depleted iron stores are associated with inspiratory muscle weakness independently of skeletal muscle mass in men with systolic chronic heart failure.

BACKGROUND: Skeletal and respiratory muscle dysfunction constitutes an important pathophysiological feature of heart failure (HF). We assessed the relationships between respiratory muscle function, skeletal muscle mass, and physical fitness in men with HF with reduced left ventricular ejection fraction (HFrEF), and investigated the hypothesis of whether iron deficiency (ID) contributes to respiratory muscle dysfunction in these patients. METHODS: We examined 53 male outpatients with stable HFrEF without asthma or chronic obstructive pulmonary disease (age: 64 ± 10 years; New York Heart Association [NYHA] class I/II/III: 36/51/13%; ischaemic aetiology: 83%; all with left ventricular ejection fraction ≤40%) and 10 middle-aged healthy men (control group). We analysed respiratory muscle function (maximal inspiratory and expiratory pressure at the mouth [MIP and MEP, respectively]), appendicular lean mass/body mass index (ALM/BMI; ALM was measured using dual-energy X-ray absorptiometry), physical fitness (components of Functional Fitness Test for Older Adults), and iron status. RESULTS: MIP, MEP, and ALM/BMI (but not MIP adjusted for ALM/BMI) were lower in men with HFrEF vs. healthy men. MIP, MEP, and MIP adjusted for ALM/BMI (but not ALM/BMI) were lower in men with HFrEF with vs. without ID. In a multivariable linear regression model lower serum ferritin (but not transferrin saturation) was associated with lower MIP independently of ALM/BMI, left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and haemoglobin concentration. In multivariable linear regression models, lower MIP was associated with worse results in Functional Fitness Test when adjusted for ALM/BMI or relevant clinical variables (NYHA class, estimated glomerular filtration rate, NT-proBNP, and haemoglobin concentration). CONCLUSIONS: In men with HFrEF, low ferritin reflecting depleted iron stores is associated with inspiratory muscle weakness independently of skeletal muscle mass. Inspiratory muscle dysfunction correlates with worse physical fitness independently of either skeletal muscle mass or disease severity.

Oxygen consumption of respiratory muscles in patients with COPD.

We measured the oxygen consumption (VO2) of respiratory muscles in 8 COPD patients and 12 age-matched healthy subjects using a closed circuit device which allows a continuous increase in external dead space and is equipped with a 9-L Collins spirometer. Furthermore, we measured simultaneously mouth occlusion pressure at 0.1 s of inspiration (P0.1), minute ventilation (VE), and other ventilatory parameters during the measurement of total VO2 (VO2 tot). We found that the logarithm of VO2tot (logVO2tot) had a good correlation with VE in both groups. The mean slope of the regression line of logVO2tot and VE (delta logVO2tot/delta VE) of COPD patients was significantly higher than that of normal subjects (p < 0.001). However, the mean Y-intercept (metabolic VO2[VO2met]) of the regression lines did not differ between the two groups. The P0.1 in COPD patients was higher than that in normal subjects at the corresponding dead space loading. However, the VE did not differ between the two groups except for at rest and the first 1 min after dead space loading. These results suggest that the VO2 of respiratory muscles in patients with COPD is higher at given ventilation compared with that in age-matched normal subjects and that this increased VO2 partly may be due to an augmented ventilatory drive.

[Mechanical and metabolic reproducibility of resistance test of expiratory muscles with incremental threshold loading]. / Reproducibilidad mecánica y metabólica de la prueba de resistencia de los músculos espiratorios con cargas umbrales incrementales.

BACKGROUND: The study of respiratory muscle endurance has mainly focused on inspiratory muscles. A new method to measure expiratory muscle endurance, through incremental threshold loading using a weighted plunger valve, has recently been described. OBJECTIVES: To evaluate the mechanical features of the plunger valve and the reproducibility of the method from the standpoint of both mechanics and metabolism. METHODS: Four untrained healthy subjects performed an incremental test with expiratory threshold loading (50 g every 2 min) on each of three non-consecutive days; each test continued until the subject could no longer open the valve. Mouth pressure was recorded continuously during each test; on the first two test days, oxygen consumption (VO2) was also measured. RESULTS: Opening and closing pressures were the same and were independent of expiratory flow, with a linear load-pressure relationship (4 cmH2O) for every 10 g of weight). The maximal tolerated load (MTL) in the three tests was stable for two of the subjects, whereas the maximal load was reached by the other two subjects in the second and third tests, respectively. When MTL was reached in the third test, mean and peak mouth pressures (the latter expressed as percent of maximal expiratory pressure [MEP]) were 49 +/- 4% and 71 +/- 4%, respectively; the expiratory tension-time index measured at the mouth ([PMEANmouth/MEP] x [TE/Ttot]) was 0.25 +/- 0.02 (TE: expiratory time; Ttot: total time). In the first and second tests, we also measured oxygen consumption of the recruited muscles, which were mainly the expiratory muscles (VO2respmax); consumption in the last test was 213 +/- 65 ml O2/min (2.9 +/- 1.1 ml O2/kg/min). The intraindividual coefficient of variation ranged from 6.3% to 19.5% for the mechanical parameters and from 14% to 21% for the metabolic ones. CONCLUSIONS: The expiratory endurance test using a threshold valve allows quantification of muscle and metabolic reserve under incremental expiratory loads. The valve has appropriate mechanical characteristics for this purpose and reproducibility is acceptable, through the precise determination of the may require up to three tests.

Target-flow inspiratory muscle training: breathing patterns and metabolic costs.

In target-flow inspiratory muscle training (TF-IMT), the generated inspiratory mouth pressure and the duration of the inspiration and expiration are standardized to given an adequate training stimulus to the inspiratory muscles. The acute effects of TF-IMT on the efficiency of breathing were studied in a group of 12 COPD patients with a ventilatory limitation of their exercise capacity (mean age 58, mean FEV1 46.2% of predicted) and in 15 normal subjects (mean age 30). Also, the effect of a 10 week period of TF-IMT on the maximal inspiratory mouth pressure (PImax) in the COPD patients was measured. After an unloaded baseline period, the subjects started to inspire through a target-flow device during 15 min, followed by a recovery phase of 5 min. During TF-IMT minute ventilation (VE) decreased only in the COPD group. The ventilatory equivalent for O2 (VE/VO2) and the dead space to tidal volume ratio (VD/VT) decreased in both groups. During recovery, VE, VE/VO2 and VD/VT remained below baseline values in the COPD group, but not in the control group. PCO2 and lactate concentrations did not change during TF-IMT. After the 10 week training period, PImax [means) (SD] increased from 5.7(2.2) to 8.2(2.7) kPa (p less than 0.05). The results indicate that with standardized TF-IMT, the inspiratory muscles can be trained effectively in COPD patients with a ventilatory limitation. The persistence of the decrease in VE, VE/VO2 and VD/VT after a training session may be an additional beneficial effect of TF-IMT.

The effect of inspiratory muscle fatigue on breathing pattern and ventilatory response to CO2.

1. The effects of inducing inspiratory muscle fatigue on the subsequent breathing pattern were examined during resting unstimulated breathing and during CO2 rebreathing. In addition, we examined whether induction of inspiratory muscle fatigue alters CO2 responsiveness. 2. Global inspiratory muscle fatigue and diaphragmatic fatigue were achieved by having subjects breathe against an inspiratory resistive load while generating a predetermined fraction of either their maximal mouth pressure or maximal transdiaphragmatic pressure until they were unable to generate the target pressure. 3. Induction of inspiratory muscle fatigue had no effect on the subsequent breathing pattern during either unstimulated breathing or during CO2 rebreathing. 4. Following induction of inspiratory muscle fatigue, the slope of the ventilatory response to CO2 was significantly decreased from 18.8 +/- 3.3 during control to 13.8 +/- 2.1 l min-1 (% end-tidal CO2 concentration)-1 with fatigue (P < 0.02).

Inspiratory muscle strength is a determinant of maximum oxygen consumption in chronic heart failure.

OBJECTIVE: To investigate the significance of respiratory muscle weakness in chronic heart failure and its relation both to maximum oxygen consumption during cardiopulmonary exercise testing and to skeletal muscle (quadriceps) strength. SUBJECTS: Seven healthy men aged 54.9 (SEM 4.3) years and 20 men with chronic heart failure aged 61.4 (1.6) years (P = 0.20) with radionuclide left ventricular ejection fraction of 25.4 (3.0)%. METHODS: Mouth pressures during maximum static inspiratory effort (PImax) at functional residual capacity (FRC) and residual volume (RV) were measured in all subjects and taken as indices of inspiratory muscle strength. Similarly, mouth pressures during maximum static expiratory effort (PEmax) at FRC and total lung capacity (TLC) were taken as indices of expiratory muscle strength. Cardiopulmonary exercise testing was performed in all subjects. All controls and 15 heart failure patients also had their right quadriceps muscle strength measured. RESULTS: There was respiratory muscle weakness in heart failure patients, with reduction of PImax at FRC (59.7) (6.3) v 85.6 (9.6) cm H2O, P = 0.045), PEmax at FRC (94.8 (6.2) v 134.6 (9.1) cm H2O, P = 0.004), and PEmax at TLC (121.7 (8.5) v 160.7 (13) cm H2O, P = 0.028). PImax at RV was also reduced but this did not reach statistical significance (77.3 (6.6) v 89.3 (13) cm H2O, P = 0.44). There was also significant weakness of the right quadriceps muscle (308.5 (22) v 446.2 (28) N, P = 0.001). PImax at both FRC and RV correlated with maximum oxygen consumption (r = 0.59, P = 0.006, and r = 0.45, P = 0.048 respectively) but not PEmax. There was, however, no significant correlation between PImax and right quadriceps strength. CONCLUSIONS: Respiratory muscle weakness is seen in chronic heart failure. The results suggest that inspiratory muscles are important in determining maximum oxygen consumption and exercise tolerance in these patients. The lack of correlation between respiratory and right quadriceps muscle strength further suggests that the magnitude and time course of respiratory and locomotor muscle weakness may differ in individual patients. Treatment aimed at improving the function of the involved muscle groups may alleviate symptoms.