Mechanical ventilation in a conscious male during exercise: A case report.

We recently explored the cardiopulmonary interactions during partial unloading of the respiratory muscles during exercise. Expanding upon this work, we present a noteworthy case study whereby we eliminated the influence of respiration on cardiac function in a conscious but mechanically ventilated human during exercise. This human was a young healthy endurance-trained male who was mechanically ventilated during semi-recumbent cycle exercise at 75 Watts (W) (~30% Wmax). During mechanically ventilated exercise, esophageal pressure was reduced to levels indistinguishable from the cardiac artefact which led to a 94% reduction in the work of breathing. The reduction in respiratory pressures and respiratory muscle work led to a decrease in cardiac output (-6%), which was due to a reduction in stroke volume (-13%), left ventricular end-diastolic volume (-15%) and left-ventricular end-systolic volume (-17%) that was not compensated for by heart rate. Our case highlights the influence of extreme mechanical ventilation on cardiac function while noting the possible presence of a maximal physiological limit to which respiration (and its associated pressures) impacts cardiac function when the work of breathing is maximally reduced.

Quantifying Diaphragm Blood Flow With Contrast-Enhanced Ultrasound in Humans.

BACKGROUND: Despite the known interplay between blood flow and function, there is currently no minimally invasive method to monitor diaphragm hemodynamics. We used contrast-enhanced ultrasound (CEUS) to quantify relative diaphragm blood flow (Q˙DIA) in humans and assessed the technique's efficacy and reliability during graded inspiratory pressure threshold loading. We hypothesized that: (1) Q˙DIA would linearly increase with pressure generation: and (2) that there would be good test-retest reliability and interanalyzer reproducibility. RESEARCH QUESTION: Can the first minimally invasive method to measure relative diaphragm blood flow be validated in humans? STUDY DESIGN AND METHODS: Quantitative contrast-enhanced ultrasound of the costal diaphragm was performed in healthy participants (10 male subjects, 6 female subjects; mean age 28 ± 5 years; BMI 22.8 ± 2.0 kg/m) during unloaded breathing and three stages of loaded breathing on two separate days. Gastric and esophageal balloon catheters measured diaphragmatic pressure. Ultrasonography was performed during a constant-rate IV infusion of lipid-stabilized microbubbles following each stage. Ultrasound images were acquired after a destruction-replenishment sequence and diaphragm specific time-intensity data were used to determine Q˙DIA by two individuals. RESULTS: Transdiaphragmatic pressure for unloaded and each loading stage were 15.2 ± 0.8, 26.1 ± 0.8, 34.6 ± 0.8, and 40.0 ± 0.8 percentage of the maximum, respectively. Q˙DIA increased with each stage of loading (3.1 ± 3.1, 6.9 ± 3.6, 11.0 ± 4.9, and 13.5 ± 5.4 AU/s; P < .0001). The linear relationship between diaphragmatic flow and pressure was reproducible from day to day. Q˙DIA had good to excellent test-retest reliability (0.86 [0.77, 0.92]; P < .0001) and excellent interanalyzer reproducibility (0.93 [0.90, 0.95]; P < .0001) with minimal bias. INTERPRETATION: Relative Q˙DIA measurements have valid physiological underpinnings, are reliable day to day, and reproducible analyzer-to-analyzer. Contrast-enhanced ultrasound is a viable, minimally invasive method for assessing costal Q˙DIA in humans and may provide a tool to monitor diaphragm hemodynamics in clinical settings.

Traditional versus dynamic sitting: Lumbar spine kinematics and pain during computer work and activity guided tasks.

Dynamic sitting may mitigate low back pain during prolonged seated work. The current study compared pelvis and lumbar spine kinematics, pain, and work productivity, in traditional and dynamic sitting. Sixteen participants completed three 20-min blocks of computer work and activity guided tasks in a traditional office chair or backless and multiaxial rotating seat pan while kinematics were measured from accelerometers on the low back. Pain ratings were recorded on a visual analogue scale every 10 min. Similar pelvis and lumbar kinematics emerged when performing computer work in traditional and dynamic sitting. Pelvis and lumbar sagittal and frontal plane shifts and fidgets were largest for dynamic sitting in the activity guided tasks. Buttocks pain was higher in dynamic sitting, but low back pain and work productivity were unaffected. Dynamic sitting increased spine movement during activity guided tasks, without negatively impacting lumbar kinematics, low back pain, or productivity during seated computer work.

Ventilatory response of peripheral chemoreceptors to hypercapnia during exercise above the respiratory compensation point.

Peripheral hypercapnic chemosensitivity (PHC) is assessed as the change in ventilation in response to a rapid change in carbon dioxide pressures (PCO2). The increase in chemoresponse from rest to sub-respiratory compensation point (RCP) exercise intensities is well-defined but less clear at intensities above the RCP when changes in known ventilatory stimulants occur. Twenty healthy subjects (n=10 females) completed a maximal exercise test on one day and on a subsequent day, transient hypercapnia was used to test PHC at multiple exercise stages. The transient hypercapnia involved two breaths of 10% CO2 repeated five times during each of the following: sitting at rest on the cycle ergometer, cycling at 40% Wmax, cycling at 85% Wmax, at rest on the cycle ergometer immediately following the 85% stage, and cycling at 40% Wmax again following the post-exercise rest. The PHC was not different across exercise intensities (0.98±0.37 vs. 0.91±0.39 vs. 0.92±0.42 L min-1 mmHg-1 for 1st 40% Wmax, 85% Wmax, and 2nd 40% Wmax, respectively (p=0.45). There were no differences in PHC between pre-supra-RCP exercise rest and post-supra-RCP exercise rest (0.52±0.23 vs. 0.53±0.24 L min-1 mmHg-1, p=0.8003). Using a repeated measures correlation to account for within participants changes, there was a significant relationship between the end-tidal PCO2 and PHC for the 85% intensity (r=0.5, p<0.0001) when end-tidal PCO2 was dynamic between the trials. We conclude that the physiological changes (e.g. metabolic milieu, temperature, etc) produced with supra-RCP exercise do not further augment PHC, and that the pre-stimulus end-tidal PCO2 modulates the PHC.

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.

The pulmonary physiology of exercise.

The pulmonary system is the first and last "line of defense" in terms of maintaining blood gas homeostasis during exercise. Our review provides the reader with an overview of how the pulmonary system responds to acute exercise. We undertook this endeavor to provide a companion article to "Cardiovascular Response to Exercise," which was published in Advances in Physiological Education. Together, these articles provide the readers with a solid foundation of the cardiopulmonary response to acute exercise in healthy individuals. The intended audience of this review is level undergraduate or graduate students and/or instructors for such classes. By intention, we intend this to be used as an educational resource and seek to provide illustrative examples to reinforce topics as well as highlight uncertainty to encourage the reader to think "beyond the textbook." Our treatment of the topic presents "classic" concepts along with new information on the pulmonary physiology of healthy aging.NEW & NOTEWORTHY Our narrative review is written with the student of the pulmonary physiology of exercise in mind, be it a senior undergraduate or graduate student or those simply refreshing their knowledge. We also aim to provide examples where the reader can incorporate real scenarios.

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.

Dysanapsis is not associated with exertional dyspnoea in healthy male and female never-smokers aged 40 years and older.

In healthy adults, airway-to-lung (i.e., dysanapsis) ratio is lower and dyspnoea during exercise at a given minute ventilation (V̇E) is higher in females than in males. We investigated the relationship between dysanapsis and sex on exertional dyspnoea in healthy adults. We hypothesized that females would have a smaller airway-to-lung ratio than males and that exertional dyspnoea would be associated with airway-to-lung ratio in males and females. We analyzed data from n = 100 healthy never-smokers aged ≥40 years enrolled in the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who underwent pulmonary function testing, a chest computed tomography scan, and cardiopulmonary exercise testing. The luminal area of the trachea, right main bronchus, left main bronchus, right upper lobe, bronchus intermedius, left upper lobe, and left lower lobe were 22%-37% smaller (all p < 0.001) and the airway-to-lung ratio (i.e., average large conducting airway diameter relative to total lung capacity) was lower in females than in males (0.609 ± 0.070 vs. 0.674 ± 0.082; p < 0.001). During exercise, there was a significant effect of V̇E, sex, and their interaction on dyspnoea (all p < 0.05), indicating that dyspnoea increased as a function of V̇E to a greater extent in females than in males. However, after adjusting for age and total lung capacity, there were no significant associations between airway-to-lung ratio and measures of exertional dyspnoea, regardless of sex (all r < 0.34; all p > 0.05). Our findings suggest that sex differences in airway size do not contribute to sex differences in exertional dyspnoea.

Quadriceps fatigue during hypoxic and ischemic knee-extension exercise is similar in males and females.

Hypoxia is known to increase muscle fatigue via both central and peripheral mechanisms. Females are typically less fatigable than males during isometric fatiguing contractions due to greater peripheral blood flow. However, sex differences in fatigue are blunted during dynamic fatiguing tasks. Thus, this study determined the interactions of sex and hypoxia on knee extensor muscle contractile function during a dynamic, ischemic fatiguing contraction. Electrical stimulation was used to determine contractile properties of the knee extensor muscles in eight males and eight females before and after an ischemic, dynamic fatiguing task while inspiring room air or a hypoxic gas mixture (10% O2:90% N2). Fatigue (assessed as time-to-task failure) was ∼10% greater during the hypoxic condition (94.3 ± 33.4 s) compared with normoxic condition (107.0 ± 42.8 s, P = 0.041) and ∼40% greater for females than males (77.1 ± 18.8 vs. 124.2 ± 38.7, P < 0.001). Immediately after the dynamic fatiguing task, there were reductions in maximal voluntary contraction force (P = 0.034) and electrically evoked twitch force (P < 0.001), and these reductions did not differ based on sex or inspirate. Cerebral tissue oxygenation showed a significant interaction of time and inspirate (P = 0.003) whereby it increased during normoxia and remained unchanged in hypoxia. No sex-related differences in the changes of cerebral tissue oxygenation were observed (P = 0.528). These data suggest that acute hypoxia increases central fatigue during ischemic single-leg exercise resulting in earlier exercise termination, but the effect does not differ based on sex.NEW & NOTEWORTHY Hypoxia exacerbates fatigue via central mechanisms after ischemic single-leg exercise. The greater fatigue observed during ischemic dynamic fatiguing exercise with hypoxia inspirate did not differ between the sexes. Hypoxia-induced central limitations are present in acute ischemic exercise and do not appear different in males and females.

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.

Attenuated cardiac autonomic function in humans with high-affinity hemoglobin and compensatory polycythemia.

During hypoxic exposure, humans with high-affinity hemoglobin (and compensatory polycythemia) have blunted increases in heart rate compared with healthy humans with typical oxyhemoglobin dissociation curves. This response may be associated with altered autonomic control of heart rate. Our hypothesis-generating study aimed to investigate cardiac baroreflex sensitivity and heart rate variability among nine humans with high-affinity hemoglobin [6 females, O2 partial pressure at 50% [Formula: see text] (P50) = 16 ± 1 mmHg] compared with 12 humans with typical affinity hemoglobin (6 F, P50 = 26 ± 1 mmHg). Participants breathed normal room air for a 10-min baseline, followed by 20 min of isocapnic hypoxic exposure, designed to lower the arterial partial pressure O2 ([Formula: see text]) to ∼50 mmHg. Beat-by-beat heart rate and arterial blood pressure were recorded. Data were averaged in 5-min periods throughout the hypoxia exposure, beginning with the last 5 min of baseline in normoxia. Spontaneous cardiac baroreflex sensitivity and heart rate variability were determined using the sequence method and the time and frequency domain analyses, respectively. Cardiac baroreflex sensitivity was lower in humans with high-affinity hemoglobin than controls at baseline and during isocapnic hypoxic exposure (normoxia: 7 ± 4 vs. 16 ± 10 ms/mmHg, hypoxia minutes 15-20: 4 ± 3 vs. 14 ± 11 ms/mmHg; group effect: P = 0.02, high-affinity hemoglobin vs. control, respectively). Heart rate variability calculated in both the time (standard deviation of the N-N interval) and frequency (low frequency) domains was lower in humans with high-affinity hemoglobin than in controls (all P < 0.05). Our data suggest that humans with high-affinity hemoglobin may have attenuated cardiac autonomic function.

The Impact of Acetazolamide and Methazolamide on Exercise Performance in Normoxia and Hypoxia.

Doherty, Connor J., Jou-Chung Chang, Benjamin P. Thompson, Erik R. Swenson, Glen E. Foster, and Paolo B. Dominelli. The impact of acetazolamide and methazolamide on exercise performance in normoxia and hypoxia. High Alt Med Biol. 24:7-18, 2023.-Carbonic anhydrase (CA) inhibitors are commonly prescribed for acute mountain sickness (AMS). In this review, we sought to examine how two CA inhibitors, acetazolamide (AZ) and methazolamide (MZ), affect exercise performance in normoxia and hypoxia. First, we briefly describe the role of CA inhibition in facilitating the increase in ventilation and arterial oxygenation in preventing and treating AMS. Next, we detail how AZ affects exercise performance in normoxia and hypoxia and this is followed by a discussion on MZ. We emphasize that the overarching focus of the review is how the two drugs potentially affect exercise performance, rather than their ability to prevent/treat AMS per se, their interrelationship will be discussed. Overall, we suggest that AZ hinders exercise performance in normoxia, but may be beneficial in hypoxia. Based upon head-to-head studies of AZ and MZ in humans on diaphragmatic and locomotor strength in normoxia, MZ may be a better CA inhibitor when exercise performance is crucial at high altitude.

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.

Effects of Face Masks on the Multiple Dimensions and Neurophysiological Mechanisms of Exertional Dyspnea.

INTRODUCTION: During the coronavirus disease 2019 pandemic, public health officials widely adopted the use of face masks (FM) to minimize infections. Despite consistent evidence that FMs increase dyspnea, no studies have examined the multidimensional components of dyspnea or their underlying physiological mechanisms. METHODS: In a randomized crossover design, 16 healthy individuals ( n = 9 women, 25 ± 3 yr) completed incremental cycling tests over three visits, where visits 2 and 3 were randomized to either surgical FM or no mask control. Dyspnea intensity and unpleasantness were assessed throughout exercise (0-10 Borg scale), and the Multidimensional Dyspnea Profile was administered immediately after exercise. Crural diaphragmatic EMG and esophageal pressure were measured using a catheter to estimate neural respiratory drive and respiratory muscle effort, respectively. RESULTS: Dyspnea unpleasantness was significantly greater with the FM at the highest equivalent submaximal work rate achieved by a given participant in both conditions (iso-work; 5.9 ± 1.7 vs 3.9 ± 2.9 Borg 0-10 units, P = 0.007) and at peak exercise (7.8 ± 2.1 vs 5.9 ± 3.4 Borg 0-10 units, P = 0.01) with no differences in dyspnea intensity ratings throughout exercise compared with control. There were significant increases in the sensory quality of "smothering/air hunger" ( P = 0.01) and the emotional response of "anxiousness" ( P = 0.04) in the FM condition. There were significant increases in diaphragmatic EMG and esophageal pressure at select submaximal work rates, but no differences in heart rate, pulse oximetry-derived arterial oxygen saturation, or breathing frequency throughout exercise with FMs compared with control. FMs significantly reduced peak work rate and exercise duration (both P = 0.02). CONCLUSIONS: FMs negatively impact the affective domain of dyspnea and increase neural respiratory drive and respiratory muscle effort during exercise, although the impact on other cardiorespiratory responses are minimal.

The effect of proportional assist ventilation on the electrical activity of the human diaphragm during exercise.

NEW FINDINGS: What is the central question of this study? What is the effect of lowering the normally occurring work of breathing on the electrical activity and pressure generated by the diaphragm during submaximal exercise in healthy humans? What is the main finding and its importance? Ventilatory assist during exercise elicits a proportional lowering of both the work performed by the diaphragm and diaphragm electrical activity. These findings have implications for exercise training studies using proportional assist ventilation to reduce diaphragm work in patients with cardiopulmonary disease. ABSTRACT: We hypothesized that when a proportional assist ventilator (PAV) is applied in order to reduce the pressure generated by the diaphragm, there would be a corresponding reduction in electrical activity of the diaphragm. Healthy participants (five male and four female) completed an incremental cycle exercise test to exhaustion in order to calculate workloads for subsequent trials. On the experimental day, participants performed submaximal cycling, and three levels of assisted ventilation were applied (low, medium and high). Ventilatory parameters, pulmonary pressures and EMG of the diaphragm (EMGdi ) were obtained. To compare the PAV conditions with spontaneous breathing intervals, ANOVA procedures were used, and significant effects were evaluated with a Tukey-Kramer test. Significance was set at P < 0.05. The work of breathing was not different between the lowest level of unloading and spontaneous breathing (P = 0.151) but was significantly lower during medium (25%, P = 0.02) and high (36%, P < 0.001) levels of PAV. The pressure-time product of the diaphragm (PTPdi ) was lower across PAV unloading conditions (P < 0.05). The EMGdi was significantly lower in medium and high PAV conditions (P = 0.035 and P < 0.001, respectively). The mean reductions of EMGdi with PAV unloading were 14, 22 and 39%, respectively. The change in EMGdi for a given lowering of PTPdi with the PAV was significantly correlated (r = 0.61, P = 0.01). Ventilatory assist during exercise elicits a reduction in the electrical activity of the diaphragm, and there is a proportional lowering of the work of breathing. Our findings have implications for exercise training studies using assisted ventilation to reduce diaphragm work in patients with cardiopulmonary disease.

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.