Tidal expiratory flow limitation during exercise is unrelated to peripheral hypercapnic chemosensitivity.

We sought to determine if peripheral hypercapnic chemosensitivity is related to expiratory flow limitation (EFL) during exercise. Twenty participants completed one testing day which consisted of peripheral hypercapnic chemosensitivity testing and a maximal exercise test to exhaustion. The chemosensitivity testing consisting of two breaths of 10% CO2 (O2∼21%) repeated 5 times during seated rest and the first 2 exercise intensities during the maximal exercise test. Following chemosensitivity testing, participants continued cycling with the intensity increasing 20 W every 1.5 minutes till exhaustion. Maximal expiratory flow-volume curves were derived from forced expiratory capacity maneuvers performed before and after exercise at varying efforts. Inspiratory capacity maneuvers were performed during each exercise stage to determine EFL. There was no difference between the EFL and non-EFL hypercapnic chemoresponse (mean response during exercise 0.96 ± 0.46 and 0.91 ± 0.33 l min-1 mmHg-1, p=0.783). Peripheral hypercapnic chemosensitivity during mild exercise does not appear to be related to the development of EFL during exercise.

Supramaximal Testing to Confirm the Achievement of V̇O 2max in Acute Hypoxia.

PURPOSE: We sought to determine if supramaximal exercise testing confirms the achievement of V̇O 2max in acute hypoxia. We hypothesized that the incremental and supramaximal V̇O 2 will be sufficiently similar in acute hypoxia. METHODS: Twenty-one healthy adults (males n = 13, females n = 8) completed incremental and supramaximal exercise tests in normoxia and acute hypoxia (fraction inspired oxygen = 0.14) separated by at least 48 h. Incremental exercise started at 80 and 60 W in normoxia and 40 and 20 W in hypoxia for males and females, respectively, with all increasing by 20 W each minute until volitional exhaustion. After a 20-min postexercise rest period, a supramaximal test at 110% peak power until volitional exhaustion was completed. RESULTS: Supramaximal exercise testing yielded a lower V̇O 2 than incremental testing in hypoxia (3.11 ± 0.78 vs 3.21 ± 0.83 L·min -1 , P = 0.001) and normoxia (3.71 ± 0.91 vs 3.80 ± 1.02 L·min -1 , P = 0.01). Incremental and supramaximal V̇O 2 were statistically similar, using investigator-determined equivalence bounds ±150 mL·min -1 , in hypoxia ( P = 0.02, 90% confidence interval [CI] = 0.05-0.14) and normoxia ( P = 0.03, 90% CI = 0.01-0.14). Likewise, using ±2.1 mL·kg -1 ·min -1 bounds, incremental and supramaximal V̇O 2 values were statistically similar in hypoxia ( P = 0.04, 90% CI = 0.70-2.0) and normoxia ( P = 0.04, 90% CI = 0.30-2.0). CONCLUSIONS: Despite differences in the oxygen cascade, incremental and supramaximal V̇O 2 values were statistically similar in both hypoxia and normoxia, demonstrating the utility of supramaximal verification of V̇O 2max in the setting of acute hypoxia.

Peripheral hypercapnic chemosensitivity at rest and progressive exercise intensities in males and females.

Peripheral hypercapnic chemosensitivity (PHC) is the ventilatory response to hypercapnia and is enhanced with acute whole body exercise. However, little is known about the mechanism(s) responsible for the exercise-related increase in PHC and if progressive exercise leads to further augmentation. We hypothesized that unloaded cycle exercise (0 W) would increase PHC but progressively increasing the intensity would not further augment the response. Twenty healthy subjects completed two testing days. Day 1 was a maximal exercise test on a cycle ergometer to determine peak power output (Wmax). Day 2 consisted of six 12-min stages: 1) rest on chair, 2) rest on bike, 3) 0 W unloaded cycling, 4) 25% Wmax, 5) 50% Wmax, and 6) ∼70% Wmax with ∼10 min of rest between each exercise stage. In each stage, PHC was assessed via two breaths of 10% CO2 (∼21% O2) repeated five times with ∼45 s between each to ensure end-tidal CO2 ([Formula: see text]) and ventilation returned to baseline. Prestimulus [Formula: see text] was not different between rest and unloaded cycling (P = 0.478). There was a significant increase in PHC between seated rest and 25% Wmax (0.71 ± 0.37 vs. 1.03 ± 0.52 L·mmHg-1·min-1, respectively, P = 0.0006) and between seated rest and unloaded cycling (0.71 ± 0.37 vs. 1.04 ± 0.4 L·mmHg-1·min-1, respectively, P = 0.0017). There was no effect of exercise intensity on PHC (1.03 ± 0.52 vs. 0.95 ± 0.58 vs. 1.01 ± 0.65 L·mmHg-1·min-1 for 25, 50, and 70% Wmax, P = 0.44). The increased PHC response from seated rest to unloaded and 25% Wmax, but no effect of exercise intensity suggests a possible feedforward/feedback mechanism causing increased PHC sensitivity through the act of cycling.NEW & NOTEWORTHY Unloaded exercise significantly increased the peripheral hypercapnic ventilatory response (HCVR) compared with rest. However, increases in exercise intensity did not further augment peripheral HCVR. Males had a greater peripheral HCVR compared with females, but there was no interaction between sex and intensity. The lack of sex interactions suggests the mechanism augmenting the peripheral HCVR with exercise is independent of sex. The increase in peripheral HCVR with exercise is likely due to central command.

Attenuating intrathoracic pressure swings decreases cardiac output at different intensities of exercise.

Intrathoracic pressure (ITP) swings that permit spontaneous ventilation have physiological implications for the heart. We sought to determine the effect of respiration on cardiac output ( Q ̇ $\dot Q$ ) during semi-supine cycle exercise using a proportional assist ventilator to minimize ITP changes and lower the work of breathing (Wb ). Twenty-four participants (12 females) completed three exercise trials at 30%, 60% and 80% peak power (Wmax ) with unloaded (using a proportional assist ventilator, PAV) and spontaneous breathing. Intrathoracic and intraabdominal pressures were measured with balloon catheters placed in the oesophagus and stomach. Left ventricular (LV) volumes and Q ̇ $\dot Q$ were determined via echocardiography. Heart rate (HR) was measured with electrocardiogram and a customized metabolic cart measured oxygen uptake ( V ̇ O 2 ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}}}$ ). Oesophageal pressure swings decreased from spontaneous to PAV breathing by -2.8 ± 3.1, -4.9 ± 5.7 and -8.1 ± 7.7 cmH2 O at 30%, 60% and 80% Wmax , respectively (P = 0.01). However, the decreases in Wb were similar across exercise intensities (27 ± 42 vs. 35 ± 24 vs. 41 ± 22%, respectively, P = 0.156). During PAV breathing compared to spontaneous breathing, Q ̇ $\dot Q$ decreased by -1.0 ± 1.3 vs. -1.4 ± 1.4 vs. -1.5 ± 1.9 l min-1 (all P < 0.05) and stroke volume decreased during PAV breathing by -11 ± 12 vs. -9 ± 10 vs. -7 ± 11 ml from spontaneous breathing at 30%, 60% and 80% Wmax , respectively (all P < 0.05). HR was lower during PAV breathing by -5 ± 4 beats min-1 at 80% Wmax (P < 0.0001). Oxygen uptake decreased by 100 ml min-1 during PAV breathing compared to spontaneous breathing at 80% Wmax (P < 0.0001). Overall, attenuating ITPs mitigated LV preload and ejection, thereby suggesting that the ITPs associated with spontaneous respiration impact cardiac function during exercise. KEY POINTS: Pulmonary ventilation is accomplished by alterations in intrathoracic pressure (ITP), which have physiological implications on the heart and dynamically influence the loading parameters of the heart. Proportional assist ventilation was used to attenuate ITP changes and decrease the work of breathing during exercise to examine its effects on left ventricular (LV) function. Proportional assist ventilation with progressive exercise intensities (30%, 60% and 80% Wmax ) led to reductions in cardiac output at all intensities, primarily through reductions in stroke volume. Decreases in LV end-diastolic volume (30% and 60% Wmax ) and increases in LV end-systolic volume (80% Wmax ) were responsible for the reduction in stroke volume. The relationship between cardiac output and oxygen uptake is disrupted during respiratory muscle unloading.

The oxygen transport cascade and exercise: Lessons from comparative physiology.

Studies of animal physiology not only provide valuable knowledge for the species in question, but also offer insights into human physiology. This thought is best highlighted by the 'Krogh Principle', which states "for many problems there is an animal on which it can be most conveniently studied". This graphical review focuses on three distinct stages of the oxygen transport cascade in which human exercise physiology knowledge has been enhanced by studies carried out in animal models. We begin by exploring ventilation, and the detrimental effects of cold, dry air on the airways in two sets of elite athletes, the cross-country skier and the racing sled dog. We then discuss the transport of oxygen via hemoglobin in humans and deer mice with relatively shifted oxygen dissociation curves. Finally, we consider the technical difficulties of measuring respiratory muscle blood flow in exercising humans and how an equine model can provide an understanding of the distribution of blood flow during exercise. These cases illustrate the complementary nature of physiological studies across species.

Perception of exercise-induced dyspnea after experimentally induced breathing discomfort.

The perception of dyspnea is influenced by both physiological and psychological factors. We sought to determine whether exertional dyspnea perception could be experimentally manipulated through prior exposure to heightened dyspnea while exercising. We hypothesized that dyspnea perception during exercise would be lower following an induced dyspnea task (IDT). Sixteen healthy participants (eight females, eight males) completed two days of exercise testing. Day 1 involved an incremental cycle exercise test starting at 40 W for females and 60 W for males, increasing by 20 W each minute until volitional exhaustion. Following the maximal exercise test on Day 1, participants completed IDT, involving 5 min of exercise at 70% of peak work rate with 500 mL dead space and external resistance (i.e., 6.8 ± 2.3 cm·H2O·s-1·L-1 inspiration, 3.8 ± 0.7 cm·H2O·s-1·L-1 expiration). Day 2 consisted of an incremental exercise test identical to Day 1. At maximal exercise, there were no differences in oxygen uptake (V̇O2; 44.7 ± 7.7 vs. 46.5 ± 6.3 mL·kg-1·min-1), minute ventilation (120 ± 35 vs. 127 ± 38 L·min-1), dyspnea (6.5 [4, 8.5] vs. 6 [4.25, 8.75]), or leg discomfort (6 [5, 8.75] vs. 7 [5, 9]) between days (all p > 0.05). At 60%-80% of peak V̇O2 (V̇O2peak), dyspnea was significantly lower on Day 2 (-0.75 [-1.375, 0] for 60% and -0.5 [0, -2] for 80%, p < 0.05) despite no differences in relevant physiological variables. The onset of perceived dyspnea occurred at a significantly higher exercise intensity on Day 2 than on Day 1 (42% ± 19% vs. 51% ± 17% V̇O2peak, respectively; p < 0.05). Except for 40% V̇O2peak (p = 0.05), RPE-L was not different at any intensities nor was the onset of perceived leg discomfort different between days (38% ± 14% vs. 43% ± 10% V̇O2peak, respectively; p = 0.10). Exposure to heightened dyspnea alters exercise-induced dyspnea perception during subsequent submaximal exercise bouts.

The effect of inspiratory muscle training and detraining on the respiratory metaboreflex.

NEW FINDINGS: What is the central question of this study? Is the attenuation of the respiratory muscle metaboreflex preserved after detraining? What is the main finding and its importance? Inspiratory muscle training increased respiratory muscle strength and attenuated the respiratory muscle metaboreflex as evident by lower heart rate and blood pressure. After 5 weeks of no inspiratory muscle training (detraining), respiratory muscle strength was still elevated and the metaboreflex was still attenuated. The benefits of inspiratory muscle training persist after cessation of training, and attenuation of the respiratory metaboreflex follows changes in respiratory muscle strength. ABSTRACT: Respiratory muscle training (RMT) improves respiratory muscle (RM) strength and attenuates the RM metaboreflex. However, the time course of muscle function loss after the absence of training or 'detraining' is less known and some evidence suggest the respiratory muscles atrophy faster than other muscles. We sought to determine the RM metaboreflex in response to 5 weeks of RMT and 5 weeks of detraining. An experimental group (2F, 6M; 26 ± 4years) completed 5 weeks of RMT and tibialis anterior (TA) training (each 5 days/week at 50% of maximal inspiratory pressure (MIP) and 50% maximal isometric force, respectively) followed by 5 weeks of no training (detraining) while a control group (1F, 7M; 24 ± 1years) underwent no intervention. Prior to training (PRE), post-training (POST) and post-detraining (DETR), all participants underwent a loaded breathing task (LBT) to failure (60% MIP) while heart rate and mean arterial blood pressure (MAP) were measured. Five weeks of training increased RM (18 ± 9%, P < 0.001) and TA (+34 ± 19%, P < 0.001) strength and both remained elevated after 5 weeks of detraining (MIP-POST vs. MIP-DETR: 154 ± 31 vs. 153 ± 28 cmH2O, respectively, P = 0.853; TA-POST vs. TA-DETR: 86 ± 19 vs. 85 ± 16 N, respectively, P = 0.982). However, the rise in MAP during LBT was attenuated POST (-11 ± 17%, P = 0.003) and DETR (-9 ± 9%, P = 0.007) during the iso-time LBT. The control group had no change in MIP (P = 0.33), TA strength (P = 0.385), or iso-time MAP (P = 0.867) during LBT across all time points. In conclusion, RM and TA have similar temporal strength gains and the attenuation of the respiratory muscle metaboreflex remains after 5 weeks of detraining.

Altering magnetic field strength impacts the assessment of diaphragmatic function using cervical magnetic stimulation.

Quantifying diaphragm neuromuscular function using cervical magnetic stimulation (CMS) typically uses only a single stimulator (1-Stim) which may be inadequate to maximally stimulate the phrenic nerves. We questioned if using two stimulators (2-Stim) together alters diaphragm neuromuscular function at baseline and following inspiratory pressure threshold loading. Six (n = 3 female) healthy young participants were instrumented with esophageal and gastric balloon tipped catheters and electrodes over the 7-8th intercostal space. With either 1-Stim or 2-Stim an incremental protocol, where the stimulator intensity was progressively increased was completed prior to a series of potentiated twitches. The inspiratory threshold loading test consisted of loaded breathing to failure. Compared to 1-Stim, 2-Stim resulted in significantly greater unpotentiated Pditw and M-waves during the incremental protocol (both p < 0.01). Similarly, 2-Stim resulted in greater potentiated Pditw (31 ± 8 vs. 41 ± 9 cmH2O; p = 0.02) and M-waves (6.4 ± 2.9 vs. 8.6 ± 2.4 V; p = 0.02). Our findings suggest that CMS using 1-Stim is unlikely to generate a sufficient magnetic field to maximally stimulate the phrenic nerves and may underestimate diaphragm function.

Peripheral hypercapnic chemosensitivity in trained and untrained females and males during exercise.

Hypercapnic chemosensitivity is the response to the increased partial pressure of carbon dioxide and results from central and peripheral chemosensor stimulation. The hypercapnic chemosensitivity of the peripheral chemoreceptors is potentially impacted by acute exercise, aerobic fitness, and sex. We sought to determine the peripheral chemoresponse to transient hypercapnia at rest and during exercise in males and females of various fitness. We hypothesized that 1) higher fitness participants would have lower hypercapnic chemosensitivity compared with those with lower fitness and 2) males would have a higher chemoresponse than females. Forty healthy participants (20 females) participated in one test day involving transient hypercapnic chemosensitivity testing and a maximal exercise test. Chemosensitivity testing involved two breaths of 10% CO2 repeated five times (45 s to 1 min between repeats) at rest and the first two stages of a maximal exercise test. There was no significant difference between higher and lower aerobic fitness groups, (mean difference 0.23 ± 0.22 rest; -0.07 ± 0.04 stage 1; 0.11 ± 0.17 stage 2 L/mmHg·min) during each stage (P = 0.472). However, we saw a significant increase in the hypercapnic response during stage 1 (0.98 ± 0.4 L/mmHg·min) compared with rest (0.79 ± 0.5 L/mmHg·min; P = 0.01). Finally, at 80 W, males had a higher chemoresponse compared with females, which persisted following body surface area correction (0.56 ± 0.2 vs. 0.42 ± 0.2 L/mmHg·min·m2, for females and males respectively (P = 0.038). Our findings suggest that sex, unlike aerobic fitness, influences peripheral hypercapnic chemosensitivity and that context (i.e., rest vs. exercise) is an important consideration.NEW & NOTEWORTHY The hypercapnic chemoresponse to transient CO2 showed an increase during acute physical activity; however, this response did not persist with further increases in intensity and was not different between participants of different aerobic fitness. Males and females show a differing response to CO2 during exercise when compared with an iso-V̇co2. Our results suggest that adaptations that lead to increased aerobic fitness do not impact the hypercapnic ventilatory response but there is an effect of sex.

Therapeutic hypothermia attenuates physiologic, histologic, and metabolomic markers of injury in a porcine model of acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a lung injury characterized by noncardiogenic pulmonary edema and hypoxic respiratory failure. The purpose of this study was to investigate the effects of therapeutic hypothermia on short-term experimental ARDS. Twenty adult female Yorkshire pigs were divided into four groups (n = 5 each): normothermic control (C), normothermic injured (I), hypothermic control (HC), and hypothermic injured (HI). Acute respiratory distress syndrome was induced experimentally via intrapulmonary injection of oleic acid. Target core temperature was achieved in the HI group within 1 h of injury induction. Cardiorespiratory, histologic, cytokine, and metabolomic data were collected on all animals prior to and following injury/sham. All data were collected for approximately 12 h from the beginning of the study until euthanasia. Therapeutic hypothermia reduced injury in the HI compared to the I group (histological injury score = 0.51 ± 0.18 vs. 0.76 ± 0.06; p = 0.02) with no change in gas exchange. All groups expressed distinct phenotypes, with a reduction in pro-inflammatory metabolites, an increase in anti-inflammatory metabolites, and a reduction in inflammatory cytokines observed in the HI group compared to the I group. Changes to respiratory system mechanics in the injured groups were due to increases in lung elastance (E) and resistance (R) (ΔE from pre-injury = 46 ± 14 cmH2 O L-1 , p < 0.0001; ΔR from pre-injury: 3 ± 2 cmH2 O L-1  s- , p = 0.30) rather than changes to the chest wall (ΔE from pre-injury: 0.7 ± 1.6 cmH2 O L-1 , p = 0.99; ΔR from pre-injury: 0.6 ± 0.1 cmH2 O L-1  s- , p = 0.01). Both control groups had no change in respiratory mechanics. In conclusion, therapeutic hypothermia can reduce markers of injury and inflammation associated with experimentally induced short-term ARDS.

Evaluation of sex-based differences in airway size and the physiological implications.

Recent evidence suggests healthy females have significantly smaller central conducting airways than males when matched for either height or lung volume during analysis. This anatomical sex-based difference could impact the integrative response to exercise. Our review critically evaluates the literature on direct and indirect techniques to measure central conducting airway size and their limitations. We present multiple sources highlighting the difference between male and female central conducting airway size in both pediatric and adult populations. Following the discussion of measurement techniques and results, we discuss the functional implications of these differences in central conducting airway size, including work of breathing, oxygen cost of breathing, and how these impacts will continue into elderly populations. We then discuss a range of topics for the future direction of airway differences and the benefits they could provide to both healthy and diseased populations. Specially, these sex-differences in central conducting airway size could result in different aerosol deposition or how lung disease manifests. Finally, we detail emerging techniques that uniquely allow for high-resolution imaging to be paired with detailed physiological measures.

Impact of wearing a surgical and cloth mask during cycle exercise.

We sought to determine the impact of wearing cloth or surgical masks on the cardiopulmonary responses to moderate-intensity exercise. Twelve subjects (n = 5 females) completed three, 8-min cycling trials while breathing through a non-rebreathing valve (laboratory control), cloth, or surgical mask. Heart rate (HR), oxyhemoglobin saturation (SpO2), breathing frequency, mouth pressure, partial pressure of end-tidal carbon dioxide (PetCO2) and oxygen (PetO2), dyspnea were measured throughout exercise. A subset of n = 6 subjects completed an additional exercise bout without a mask (ecological control). There were no differences in breathing frequency, HR or SpO2 across conditions (all p > 0.05). Compared with the laboratory control (4.7 ± 0.9 cmH2O [mean ± SD]), mouth pressure swings were smaller with the surgical mask (0.9 ± 0.7; p < 0.0001), but similar with the cloth mask (3.6 ± 4.8 cmH2O; p = 0.66). Wearing a cloth mask decreased PetO2 (-3.5 ± 3.7 mm Hg) and increased PetCO2 (+2.0 ± 1.3 mm Hg) relative to the ecological control (both p < 0.05). There were no differences in end-tidal gases between mask conditions and laboratory control (both p > 0.05). Dyspnea was similar between the control conditions and the surgical mask (p > 0.05) but was greater with the cloth mask compared with laboratory (+0.9 ± 1.2) and ecological (+1.5 ± 1.3) control conditions (both p < 0.05). Wearing a mask during short-term moderate-intensity exercise may increase dyspnea but has minimal impact on the cardiopulmonary response. Novelty: Wearing surgical or cloth masks during exercise has no impact on breathing frequency, tidal volume, oxygenation, and heart rate However, there are some changes in inspired and expired gas fractions that are physiologically irrelevant. In young healthy individuals, wearing surgical or cloth masks during submaximal exercise has few physiological consequences.