Ventilatory Response To Exercise Research Articles

Inaugural Review Prize 2023: The exercise hyperpnoea dilemma: A 21st-century perspective.

During mild or moderate exercise, alveolar ventilation increases in direct proportion to metabolic rate, regulating arterial CO2 pressure near resting levels. Mechanisms giving rise to the hyperpnoea of exercise are unsettled despite over a century of investigation. In the past three decades, neuroscience has advanced tremendously, raising optimism that the 'exercise hyperpnoea dilemma' can finally be solved. In this review, new perspectives are offered in the hope of stimulating original ideas based on modern neuroscience methods and current understanding. We first describe the ventilatory control system and the challenge exercise places upon blood-gas regulation. We highlight relevant system properties, including feedforward, feedback and adaptive (i.e., plasticity) control of breathing. We then elaborate a seldom explored hypothesis that the exercise ventilatory response continuously adapts (learns and relearns) throughout life and ponder if the memory 'engram' encoding the feedforward exercise ventilatory stimulus could reside within the cerebellum. Our hypotheses are based on accumulating evidence supporting the cerebellum's role in motor learning and the numerous direct and indirect projections from deep cerebellar nuclei to brainstem respiratory neurons. We propose that cerebellar learning may be obligatory for the accurate and adjustable exercise hyperpnoea capable of tracking changes in life conditions/experiences, and that learning arises from specific cerebellar microcircuits that can be interrogated using powerful techniques such as optogenetics and chemogenetics. Although this review is speculative, we consider it essential to reframe our perspective if we are to solve the till-now intractable exercise hyperpnoea dilemma.

Defective exercise-related expiratory muscle recruitment in patients with PHOX2B mutations: A clue to neural determinants of the congenital central hypoventilation syndrome

Introduction and objectivesThe human congenital central hypoventilation syndrome (CCHS) is caused by mutations in the PHOX2B (paired-like homeobox 2B) gene. Genetically engineered PHOX2B rodents exhibit defective development of the brainstem retrotrapezoid nucleus (RTN), a carbon dioxide sensitive structure that critically controls expiratory muscle recruitment. This has been linked to a blunted exercise ventilatory response. Whether this can be extrapolated to human CCHS is unknown and represents the objective of this study. Materials and methodsThirteen adult CCHS patients and 13 healthy participants performed an incremental symptom-limited cycle cardiopulmonary exercise test. Responses were analyzed using guideline approaches (ventilation V'E, tidal volume VT, breathing frequency, oxygen consumption, carbon dioxide production) complemented by a breathing pattern analysis (i.e. expiratory and inspiratory reserve volume, ERV and IRV). ResultsA ventilatory response occurred in both study groups, as follows: V'E and VT increased in CCHS patients until 40 W and then decreased, which was not observed in the healthy participants (p<0.001). In the latter, exercise-related ERV and IRV decreases attested to concomitant expiratory and inspiratory recruitment. In the CCHS patients, inspiratory recruitment occurred but there was no evidence of expiratory recruitment (absence of any ERV decrease, p<0.001). ConclusionsAssuming a similar organization of respiratory rhythmogenesis in humans and rodents, the lack of exercise-related expiratory recruitment observed in our CCHS patients is compatible with a PHOX2B-related defect of a neural structure that would be analogous to the rodents' RTN. Provided corroboration, ERV recruitment could serve as a physiological outcome in studies aiming at correcting breathing control in CCHS.

Exercise ventilatory response after COVID-19: comparison between ambulatory and hospitalized patients.

Inefficient ventilatory response during cardiopulmonary exercise testing (CPET) has been suggested as a cause of post-COVID-19 dyspnea. It has been described in hospitalized patients (HOSP) with lung parenchymal sequelae but also after mild infection in ambulatory patients (AMBU). We hypothesize that AMBU and HOSP have different ventilatory responses to exercise, due to different etiologies. We analyzed CPET realized between July 2020 and May 2022 of patients with persisting respiratory symptoms 3 mo after COVID-19. Chest computed tomography (CT) scan, pulmonary function tests, quality of life, and respiratory questionnaires were collected. CPET data were specifically explored as a function of ventilation (V̇e) and time. Seventy-nine consecutive patients were included (42 AMBU and 37 HOSP, median: 54 [44-60] yr old, 57% female). Patients were hospitalized for a median of 20 [8-34] days, with pneumonia (41%) or acute respiratory distress syndrome (ARDS; 30%). Among HOSP, 12(32%) patients had abnormal values for spirometry and 18(51%) for carbon monoxide diffusing capacity (P < 0.001). CPET showed no differences between AMBU and HOSP in peak absolute O2 uptake (V̇o2) (1.59 [1.22-2.11] mL·min-1; P = 0.65). Tidal volume (VT) as a function of V̇e, was lower in AMBU than in HOSP (P < 0.01) toward the end of exercise. The slope of the V̇e-CO2 production was higher than normal in both groups (30.9 [26.1-34.3]; P = 0.96). In conclusion, the severity of COVID-19 did not influence the exercise capacity, but AMBU demonstrated a less efficient ventilatory response to exercise as compared with HOSP. CPET with exploration of data as a function of V̇e and throughout the exercise better unveil ventilatory inefficiency.NEW & NOTEWORTHY We evaluated the exercise ventilatory response in patients with persisting dyspnea after severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. We found that despite similar peak power and peak absolute O2 uptake, tidal volume as a function of ventilation was lower in ambulatory than in hospitalized patients toward the end of exercise, reflecting ventilatory inefficiency. We call for evaluation of minute ventilation with the exploration of data throughout the exercise and not only peak data to better unveil ventilatory inefficiency.

Patients With Myalgic Encephalomyelitis Have Blunted Exercise Ventilatory Responses In The Post-Exertional State

Patients With Myalgic Encephalomyelitis Have Blunted Exercise Ventilatory Responses In The Post-Exertional State

Impact of cyanosis on ventilatory responses during stair climb exercise in Eisenmenger syndrome and idiopathic pulmonary arterial hypertension

Studies assessing exercise ventilatory responses during real-life exercise in pulmonary arterial hypertension (PAH) which include patients with cyanotic congenital heart disease are scarce. We assessed the ventilatory response to stairclimbing in patients with idiopathic PAH (IPAH) and congenital heart disease-associated PAH with Eisenmenger (EIS) physiology compared to healthy controls. Fifteen adults with IPAH, six EIS and 15 age and body mass index (BMI) matched controls were prospectively recruited. Participants completed spirometry and a self-paced stair-climb (48 steps) with portable cardiopulmonary exercise testing (CPET) equipment in-situ. Borg dyspnoea scores were measured at rest and on stair-climb cessation. Both IPAH and EIS groups had amplified ventilatory responses compared to Controls. The rate of increase in minute ventilation (VE) was exaggerated in EIS driven by an early increase in tidal volume (Tv) and more gradual increase in respiratory rate (RR). Peak Tv, RR, Tv: forced vital capacity (FVC) ratio, VE/VCO2 slope and stairclimb duration were significantly higher in EIS and IPAH compared to controls despite similar baseline spirometry and change in oxygen uptake on exercise. A decline in end-tidal carbon dioxide (CO2) and arterial oxygen saturations in early exercise distinguished EIS and IPAH patients. Significant correlations were observed between peak exercise Borg score and stair-climb time (r = 0.73, p = 0.002), peak end-tidal CO2 (r = −0.73, p = 0.001), peak VE (r = 0.53, p = 0.008), peak RR (r = 0.42, p = 0.011) and VE/VCO2 slope (r = 0.54, p = 0.001). Patients with IPAH and EIS have exaggerated ventilatory responses to stair-climbing compared to the controls with more severe levels of dyspnoea perception in Eisenmenger syndrome for equivalent oxygen uptake and work.

Obesity Blunts the Ventilatory Response to Exercise in Men and Women.

Rationale: Obesity presents a mechanical load to the thorax, which could perturb the generation of minute ventilation (V̇e) during exercise. Because the respiratory effects of obesity are not homogenous among all individuals with obesity and obesity-related effects could vary depending on the magnitude of obesity, we hypothesized that the exercise ventilatory response (slope of the V̇e and carbon dioxide elimination [V̇co2] relationship) would manifest itself differently as the magnitude of obesity increases.Objectives: To investigate the V̇e/V̇co2 slope in an obese population that spanned across a wide body mass index (BMI) range.Methods: A total of 533 patients who presented to a surgical weight loss center for pre-bariatric surgery testing performed an incremental maximal cycling test and were studied retrospectively. The V̇e/V̇co2 slope was calculated up to the ventilatory threshold. Patients were examined in groups based on BMI (category 1: 30-39.9 kg/m2, category 2: 40-49.9 kg/m2, and category 3: ≥50 kg/m2). Because the respiratory effects of obesity could be sex and/or age specific, we further examined patients in groups by sex and age (younger: <50 yr and older: ≥50 yr). Differences in the V̇e/V̇co2 slope were then compared between BMI category, age, and sex using a three-way ANOVA.Results: No significant BMI category by sex by age interactions was detected (P = 0.75). The V̇e/V̇co2 slope decreased with increases in BMI (category 1, 29.1 ± 4.0; category 2, 28.4 ± 4.1; and category 3, 27.1 ± 3.3) and was elevated in women (28.9 ± 4.1) compared with men (26.7 ± 3.2) (BMI category by sex interaction, P < 0.05). No age-related differences were observed (BMI category by age interaction, P = 0.55). The partial pressure for end-tidal CO2 was elevated at the ventilatory threshold in BMI category 3 compared with BMI categories 1 and 2 (both P < 0.01).Conclusions: These findings suggest that obesity presents a unique challenge to augmenting ventilatory output relative to CO2 elimination, such that the increase in the exercise ventilatory response becomes blunted as the magnitude of obesity increases. Further studies are required to investigate the clinical consequences and the mechanisms that may explain the attenuation of exercise ventilatory response with increasing BMI in men and women with obesity.

Novel application of Poincaré analysis to detect and quantify exercise oscillatory ventilation

Objective. Exercise oscillatory ventilation (EOV) is frequently observed in individuals with cardiac disease. Assessment of EOV relies on pattern recognition and this subjectivity and lack of quantification limits the widespread clinical use of EOV as a prognostic marker. Poincaré analysis quantifies the short (SD1) and long-term (SD2) variability of a signal and may provide an alternative means to identify and quantify unstable exercise breathing patterns. This study aimed to determine if Poincaré analysis can distinguish between the breathing patterns of healthy control subjects and individuals being assessed for heart transplantation with and without EOV. Approach. Thirty-nine subjects performed a cardiopulmonary exercise test as part of heart transplant assessment and were subjectively classified into two groups according to the presence of EOV: non-EOV (n = 19) and EOV (n = 20). The control group (n = 24) consisted of healthy adults. Poincaré analysis (SD1 and SD2) was performed for minute ventilation ( E) and tidal volume (VT) normalized to forced vital capacity ( En and Tn ), and breathing frequency (BF) for breath-by-breath data over the 10–15 ml · min−1 · kg−1 O2 range. Main results. Poincaré analysis showed similar exercise ventilatory responses between the non-EOV and control group. BF was found to discriminate between subjects with stable and unstable ventilation. BF SD1 was significantly higher in the EOV group compared to the non-EOV (7.9 versus 4.6, p < 0.01) and control (7.9 versus 4.2, p < 0.01) groups. The EOV group had significantly greater BF SD2 compared to the non-EOV (5.7 versus 3.5, p < 0.01) and control (5.7 versus 3.5, p < 0.01) groups. Significance. We demonstrated that this novel application of Poincaré analysis can objectively distinguish and quantify unstable from stable breathing patterns during exercise. In subjects being assessed for heart transplantation the presence of EOV is associated with greater BF variability. Poincaré analysis provides an objective measure to identify and quantify EOV. Summary at a glance. As EOV may indicate abnormal ventilatory control, there is a need for an objective measure to identify and quantify unstable from stable ventilation during exercise. We developed a method of quantifying BF variation by the application of Poincaré analysis and demonstrated higher than normal variability of BF in subjects being assessed for heart transplantation who demonstrated EOV.

Ventilatory responses to constant load exercise following the inhalation of a short-acting ß2-agonist in a laboratory-controlled diesel exhaust exposure study in individuals with exercise-induced bronchoconstriction

ObjectiveIndividuals with exercise-induced bronchoconstriction (EIB) use ß2-agonists to reduce respiratory symptoms during acute exercise. The resultingbronchodilation could increase the dose of inhaled pollutants and impair respiratory function when exercise is performedin air pollution. We aimed to assess respiratory responses in individuals with EIB when completing a cycling bout while being exposed to diesel exhaust (DE) or filtered air (FA) with and without the inhalation of salbutamol (SAL), a short-acting ß2-agonist. MethodsIn a double-blind, repeated-measures design, 19 participants with EIB (22-33 years of age) completed four visits: FA-placebo (FA-PLA), FA-SAL, DE-PLA, DE-SAL. After the inhalation of either 400 µg of SAL or PLA, participants sat in the exposure chamber for 60 min, breathing either FA or DE (PM2.5 = 300 μg/m3). Participants then cycled for 30 min at 50 % of peak work rate while breathing FA or DE. Respiratory responses were assessed via spirometry, work of breathing (WOB), fractional use of ventilatory capacity (V̇E/V̇E,CAP), area under the maximal expiratory flow-volume curve (MEFVAUC), and dyspnea during and following cycling. ResultsBronchodilation in response to SAL and acute cycling was observed, independent of FA/DE exposure. Specifically, FEV1 was increased by 7.7 % (confidence interval (CI): 7.2–8.2 %; p < 0.01) in response to SAL, and MEFVAUC was increased after cycling by 1.1 % (0.9–1.3 %; p = 0.03). Despite a significant decrease in total WOB by 6.2 J/min (4.7–7.5 J/min; p = 0.049) and a reduction in V̇E/V̇E,CAP by 5.8 % (5–6 %, p < 0.01) in the SAL exposures, no changes were observed in dyspnea. The DE exposure significantly increased V̇E/V̇E,CAP by 2.4 % (0.9–3.9 %; p < 0.01), but this did not affect dyspnea. DiscussionOur findings suggest that the use of SAL prior to moderate-intensity exercise when breathing high levels of DE, does not reduce respiratory function or exercise ventilatory responses for up to 60 min following exercise.

Ventilatory Responsiveness during Exercise and Performance Impairment in Acute Hypoxia.

An adequate increase in minute ventilation to defend arterial oxyhemoglobin saturation (SpO2) during hypoxic exercise is commonly viewed as an important factor contributing to large inter-individual variations in the degree of exercise performance impairment in hypoxia. Although the hypoxic ventilatory response (HVR) could provide insight into the underpinnings of such impairments, it is typically measured at rest under isocapnic conditions. Thus, we aimed to determine whether 1) HVR at rest and during exercise are similar and 2) exercise HVR is related to the degree of impairment in cycling time trial (TT) performance from normoxia to acute hypoxia (∆TT). Sixteen endurance-trained men (V˙O2peak, 62.5 ± 5.8 mL·kg-1·min-1) performed two poikilocapnic HVR tests: one during seated rest (HVRREST) and another during submaximal cycling (HVREX). On two separate visits, subjects (n = 12) performed a 10-km cycling TT while breathing either room air (FiO2 = 0.21) or hypoxic gas mixture (FiO2 = 0.16) in a randomized order. HVREX was significantly (P < 0.001) greater than HVRREST (1.52 ± 0.47 and 0.22 ± 0.13 L·min-1·%SpO2-1, respectively), and these measures were not correlated (r = -0.16, P = 0.57). ∆TT was not correlated with HVRREST (P = 0.70) or HVREX (P = 0.54), but differences in ventilation and end-tidal CO2 between hypoxic and normoxic TT and the ventilatory equivalent for CO2 during normoxic TT explained ~85% of the variance in performance impairment in acute hypoxia (P < 0.01). We conclude that 1) HVR is not an appropriate measure to predict the exercise ventilatory response or performance impairments in acute hypoxia and 2) an adequate and metabolically matched increase in exercise ventilation, but not the gain in the ventilatory response to hypoxia, is essential for mitigating hypoxia-induced impairments in endurance cycling performance.

External dead space explains sex-differences in the ventilatory response to submaximal exercise in children with and without obesity

We compared the exercise ventilatory response (slope of the ventilation, V̇E and carbon dioxide production, V̇CO2 relationship) in boys and girls with and without obesity. 46 children with obesity (BMI percentile: 97.7 ± 1.4) and 27 children without obesity (BMI percentile: 55.1 ± 22.2) were included and divided into groups by sex (with obesity: 17 girls and 29 boys; without obesity: 13 girls and 14 boys). A 6 min constant load cycling test at 45 % of peak work rate was performed. The V̇E/V̇CO2 slope was similar (p = 0.67) between children with (32.7 ± 4.3) and without (32.2 ± 6.1) obesity; however, it was higher (p = 0.02) in girls (35.4 ± 5.6) than boys (32.6 ± 4.9). We also examined a corrected V̇E/V̇CO2 slope for the effects of mechanical dead space (VDM), by subtracting V̇DM from V̇E (V̇Ecorr/V̇CO2 slope). The V̇Ecorr/V̇CO2 slope remained similar (p = 0.37) between children with (26.8 ± 3.2) and without obesity (26.1 ± 3.1); however, no sex differences were observed (p = 0.13). Therefore, VDM should be accounted for before evaluating the V̇E/V̇CO2 slope, particularly when making between-sex comparisons.

Lasting alterations to the exercise ventilatory response in adult survivors of prematurity

IntroductionWe previously published that the ventilatory drive in adult survivors of prematurity is impaired in hypoxic conditions. Previously studies in adult survivors of prematurity demonstrate impairments in expiratory flow that limit ventilation during exercise. However, ventilatory drive during exercise has not been explored. Therefore, the purpose of this study was to evaluate the ventilatory drive during exercise, including exercise in hypoxia. We hypothesized that the ventilatory drive (VE/VCO2) to exercise would be limited in individuals born premature and not further impacted by hypoxia.MethodsPrematurely born adults (age 19–21) from the Newborn Lung Project cohort participated in two graded exercise tests breathing either 21% (normoxia) or 12% (hypoxia) oxygen. The term‐born control group was well‐matched in terms of sex, height, weight, baseline pulmonary function, and VO2max. We measured arterial blood gases, metabolism and ventilation at each workload to determine the ventilatory response to normoxic and hypoxic exercise.ResultsIn normoxic exercise, adults born prematurely have overall increased minute ventilation, compared to controls, explained by an increased frequency that compensated for their limited tidal volume. VE/VCO2 was also greater, suggesting reduced ventilatory efficiency. This is can be explained by the lower blood pH during exercise. In hypoxic exercise, the ventilatory drive in adults born prematurely is more similar to the control.ConclusionWe demonstrate the existence of a lifelong ventilation phenotype associated with prematurity that, contrary to our hypothesis, includes decreased ventilatory efficiency (increased VE/VCO2) and decreased blood pH. Prematurely‐born adults compensate for poor chemoreceptor function in hypoxic exercise via mechanisms currently being investigated by our group.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The control of ventilation during exercise: a lesson in critical thinking.

Learning the basic competencies of critical thinking are very important in the education of any young scientist, and teachers must be prepared to help students develop a valuable set of analytic tools. In my experience, this is best achieved by encouraging students to study areas with little scientific consensus, such as the control mechanisms of the exercise ventilatory response, as it can allow greater objectivity when evaluating evidence, while also giving students the freedom to think independently and problem solve. In this article, I discuss teaching strategies by which physiology, biomedical science, and sport science students can simultaneously develop their understanding of respiratory control mechanisms and learn to critically analyze evidence thoroughly. This can be best achieved by utilizing both teacher-led and student-led learning environments, the latter of which encourages the development of learner autonomy and independent problem solving. In this article, I also aim to demonstrate a systematic approach of critical assessment that students can be taught, adapt, and apply independently. Among other things, this strategy involves: 1) defining the precise phenomenon in question; 2) understanding what investigations must demonstrate to explain the phenomenon and its underlying mechanisms; 3) evaluating the explanations/mechanisms of the phenomenon and the evidence for them; and 4) forming strategies to produce strong evidence, if none exists.

Use of 'ideal' alveolar air equations and corrected end-tidal PCO2 to estimate arterial PCO2 and physiological dead space during exercise in patients with heart failure.

Arterial CO2 tension (PaCO2) and physiological dead space (VD) are not routinely measured during clinical cardiopulmonary exercise testing (CPET). Abnormal changes in PaCO2 accompanied by increased VD directly contribute to impaired exercise ventilatory function in heart failure (HF). Because arterial catheterization is not standard practice during CPET, this study tested the construct validity of PaCO2 and VD prediction models using 'ideal' alveolar air equations and basic ventilation and gas-exchangegas exchange measurements during CPET in HF. Forty-seven NYHA class II/III HF (LVEF=21±7%; age=55±9years; male=89%; BMI=28±5kg/m2) performed step-wise cycle ergometry CPET to volitional fatigue. Breath-by-breath ventilation and gas exchange were measured continuously. Steady-state PaCO2 was measured at rest and peak exercise via radial arterial catheterization. Criterion VD was calculated via 'ideal' alveolar equations, whereas PaCO2 or VD models were based on end-tidal CO2 tension (PETCO2), tidal volume (VT), and/or weight. Criterion measurements of PaCO2 (38±5 vs. 33±5mmHg, P<0.01) and VD (0.26±0.07 vs. 0.41±0.15L, P<0.01) differed at rest vs. peak exercise, respectively. The equation, 5.5+0.90×PETCO2-0.0021×VT, was the strongest predictor of PaCO2 at rest and peak exercise (bias±95%LOA=-3.24±6.63 and -0.98±5.76mmHg; R2=0.57 and 0.75, P<0.001, respectively). This equation closely predicted VD at rest and peak exercise (bias±95%LOA=-0.03±0.06 and -0.02±0.13L; R2=0.86 and 0.83, P<0.001, respectively). These data suggest predicted PaCO2 and VD based on breath-by-breath gas exchange and ventilatory responses demonstrate acceptable agreement with criterion measurements at peak exercise in HF patients. Routine assessment of PaCO2 and VD can be used to improve interpretability of exercise ventilatory responses in HF.

The Gravity-Loading countermeasure Skinsuit (GLCS) and its effect upon aerobic exercise performance

The Russian Pingvin suit is employed as a countermeasure to musculoskeletal atrophy in microgravity, though its 2-stage loading regime is poorly tolerated. The Gravity-Loading Countermeasure Skinsuit (GLCS) has been devised to comfortably compress the body via incrementally increasing longitudinal elastic-fibre tensions from the shoulders to the feet. We tested whether the Mk III GLCS was a feasible adjunct to sub-maximal aerobic exercise and resulting VO2Max predictions. Eight healthy subjects (5♂, 28±6yr) performed cycle ergometry at 75% VO2Max (derived from an Astrand-Rhyming protocol) whilst wearing a GLCS and gym clothing (GYM). Ventilatory parameters, heart rate (HR), core temperature (TC), and blood lactate (BL) were recorded along with subjective perceived exertion, thermal comfort, movement discomfort and body control. Physiological and subjective responses were compared over TIME and between GYM and GLCS (ATTIRE) with 2-way repeated measures ANOVA and Wilcoxon tests respectively. Resultant VO2Max predictions were compared with paired t-tests between ATTIRE. The GLCS induced greater initial exercise ventilatory responses which stabilised by 20min. HR and TC continued to rise from 5min irrespective of ATTIRE, whereas BL was greater in the GLCS at 20min. Predicted VO2Max did not differ with ATTIRE, though some observed differences in HR were noteworthy. All subjective ratings were exacerbated in the GLCS. Despite increased perception of workload and initial ventilatory augmentations, submaximal exercise performance was not impeded. Whilst predicted VO2Max did not differ, determination of actual VO2Max in the GLCS is warranted due to apparent modulation of the linear HR-VO2 relationship. The GLCS may be a feasible adjunct to exercise and potential countermeasure to unloaded-induced physiological deconditioning on Earth or in space.

Short-term modulation of the ventilatory response to exercise is preserved in obstructive sleep apnea

BackgroundThe ventilatory response to exercise can be transiently adjusted in response to environmentally (e.g., breathing apparatus) or physiologically altered conditions (e.g., respiratory disease), maintaining constant relative arterial PCO2 regulation from rest to exercise (Mitchell and Babb, 2006); this augmentation is called short-term modulation (STM) of the exercise ventilatory response. Obesity and/or obstructive sleep apnea could affect the exercise ventilatory response and the capacity for STM due to chronically increased mechanical and/or ventilatory loads on the respiratory system, and/or recurrent (chronic) intermittent hypoxia experienced during sleep. We hypothesized that: (1) the exercise ventilatory response is augmented in obese OSA patients compared with obese non-OSA adults, and (2) the capacity for STM with added dead space is diminished in obese OSA patients. MethodsNine obese adults with OSA (age: 39±6 yr, BMI: 40±5kg/m2, AHI: 25±24 events/h [range 6–73], mean±SD) and 8 obese adults without OSA (age: 38±10 yr, BMI: 37±6kg/m2, AHI: 1±2) completed three, 20-min bouts of constant-load submaximal cycling exercise (8min rest, 6min at 10 and 30W) with or without added external dead space (200 or 400mL; 20min rest between bouts). Steady-state measurements were made of ventilation (V˙E), oxygen consumption V˙O2), carbon dioxide production (V˙CO2), and end-tidal PCO2 (PETCO2). The exercise ventilatory response was defined as the slope of the V˙E-V˙CO2 relationship (ΔV˙E/ΔV˙CO2). ResultsIn control (i.e. no added dead space), the exercise ventilatory response was not significantly different between non-OSA and OSA groups (ΔV˙E/ΔV˙CO2 slope: 30.5±4.2 vs 30.5±3.8, p>0.05); PETCO2 regulation from rest to exercise did not differ between groups (p>0.05). In trials with added external dead space, ΔV˙E/ΔV˙CO2 increased with increased dead space (p < 0.05) and the PETCO2 change from rest to exercise remained small (<2mmHg) in both groups, demonstrating STM. There were no significant differences between groups. ConclusionsContrary to our hypotheses: (1) the exercise ventilatory response is not increased in obese OSA patients compared with obese non-OSA adults, and (2) the capacity for STM with added dead space is preserved in obese OSA and non-OSA adults.

Age and Sex Differences in the Mechanical Ventilatory Response to Exercise

Age and Sex Differences in the Mechanical Ventilatory Response to Exercise

End Tidal CO2 Regulation During Rest versus Exercise Under Beginning Conditions of Eucapnia versus Hypocapnia

PURPOSE: The exercise ventilatory response in mammals is feed forward with respect to arterial CO2 pressure (PaCO2) regulation, such that PaCO2 during exercise is regulated relative to the resting level, independent of sensory feedback. Arterial and alveolar PaCO2 are indirectly reflected by end tidal CO2 (EtCO2). These experiments employed EtCO2 measurements to examine possible differences in feed forward CO2 regulation from rest to exercise under beginning conditions of eucapnia (EC) and hypocapnia (HC). It was hypothesized that, compared to rest, normal increases in EtCO2 would be attenuated following hyperventilation induced HC to lower resting EtCO2 immediately prior to exercise, but lower EtCO2 would not persist to the same degree at rest following hyperventilation. METHODS: VO2 (ml/kg/min) and EtCO2 (mmHg) were collected on 20 subjects (n=10 males & 10 females, 20.9±0.6 y.o.) during the fifth minute of steady-state rest (baseline), and during each subsequent minute of either mild exercise (5 min. walking @ 1% grade, 4.83 k.p.h.) or further rest (5 min.) under conditions EC and HC (7 deep, rapid breaths immediately prior to exercise or further rest). Percent change from baseline EtCO2 values were determined for each minute of rest and exercise. All EH and HC conditions were compared for both rest and exercise using a one-way repeated measures ANOVA or paired t-test. Data were expressed as mean±S.E.M of % change from baseline EtCO2, and p<0.05 was considered significant. RESULTS: Hyperventilation significantly decreased EtCO2 prior to both exercise (-37±1.9%, p<0.001) and further rest (-34.2±2.1%, p<0.001). No differences in %EtCO2 change were observed between EC and HC conditions (EC %EtCO2 change - HV %EtCO2 change) within the resting or exercise measurements. EtCO2 differences between EC and HC conditions were significantly larger during exercise following hyperventilation, versus rest following hyperventilation, during the fourth minute (3.30±2.18% vs -0.91±1.52%, p=0.041) and fifth minute (4.67±2.66% vs -0.70±1.58%, p=0.034). CONCLUSIONS: EtCO2 data trends were consistent with our hypothesis. Mean EtCO2 % change remained consistently lower during five minutes of mild exercise following hyperventilation, when compared to five minutes of rest following hyperventilation, although statistical differences between rest and exercise HC and EC conditions were observed only during the fourth and fifth minutes.

Type III–IV muscle afferents are not required for steady-state exercise hyperpnea in healthy subjects and patients with COPD or heart failure

Blockade of group III–IV muscle afferents by intrathecal injection of the μ-opioid agonist fentanyl (IF) in humans has been variously reported to depress exercise hyperpnea in some studies but not others. A key unanswered question is whether such an effect is transient or persists in the steady state. Here we show that in healthy subjects undergoing constant-load cycling exercise IF significantly slows the transient exercise ventilatory kinetics but has no discernible effect on the ventilatory response when exercise is sufficiently prolonged. Thus, the ventilatory response to group III–IV muscle afferents input in healthy subjects is not a simple reflex but acts like a high-pass filter with maximum sensitivity during early-phase exercise and is reset in the late phase. In patients with chronic heart failure (CHF) IF causes sustained CO2 retention not only during exercise but also in the resting state, where muscle afferents feedback is minimal. In patients with chronic obstructive pulmonary disease (COPD), IF also elicits sustained decreases in the exercise ventilatory response but with little or no resultant CO2 retention due to concomitant decreases in physiological VD/VT (dead space-to-ventilation ratio). These results support the proposition that optimal long-term regulation of exercise hyperpnea in health and in disease is determined centrally by the respiratory controller through the continuing adaptation of an internal model which dynamically tracks the metabolic CO2 load and the ventilatory inefficiency 1/1−VD/VT that must be overcome for the maintenance of arterial PCO2 homeostasis, rather than being reflexively driven by group III–IV muscle afferents feedback per se.

Effects of altered airway function on exercise ventilation in asthmatic adults.

Variable airway function is a central feature of the asthmatic condition. Thus, habitually active asthmatics are certain to exercise under conditions of variable airway (dys)function. The purpose of this study was to determine the effects of variable preexercise airway function on ventilation during whole-body exercise in asthmatic adults. Eight mild asthmatic (age = 26 yr; V˙O2peak = 49 mL·kg·min) and nine nonasthmatic (age = 30 yr; V˙O2peak = 46 mL·kg·min) adults performed constant workrate cycling exercise to exhaustion after four separate interventions: 1) a control trial (CON); 2) inhalation of fast-acting β2-agonist (BD); 3) eucapnic voluntary hyperpnea challenge (BC); and 4) sham to the hyperpnea (SHAM). Pulmonary function was assessed at baseline and after each intervention. Exercise ventilation and operating lung volumes were compared among the four exercise trials in both control and asthmatic subjects. Baseline pulmonary function was significantly lower in asthmatic subjects compared with control subjects. In asthmatic subjects, postintervention (i.e., preexercise) forced expiratory volume 1.0 s was significantly different among the four exercise trials (CON = 3.5 ± 0.4, BD = 4.1 ± 0.4, SHAM = 3.6 ± 0.3, BC = 2.8 ± 0.3 L, P < 0.05), whereas it was not different in control subjects. There were no differences in exercise ventilation or operating lung volumes during exercise among the four trials either within asthmatic subjects or between control and asthmatic subjects. These findings suggest that the state of airway function-whether bronchodilated or bronchoconstricted-before exercise in the mild asthmatic does not affect the exercise ventilatory response. Thus, ventilatory system function in the asthmatic appears to be responsive to the acute requirement for increased airflow during whole-body exercise.

Isocapnic augmented exercise ventilation in congestive heart failure: effect of apparent (real‐feel) metabolic CO2 load in respiratory chemosensing

CO2 breathing introduces an airway CO2 load that clogs the mechanism of pulmonary CO2 elimination, inevitably causing hypercapnia when the inspired PCO2 is high enough to prohibit isocapnia regardless of the ventilation level. The control law (Comroe's law) evidencing such self‐imposed permissive hypercapnia has been dubbed “CO2 tolerance curve” (rather than CO2 response curve) by Fenn and Craig (1963). By contrast, muscular exercise introduces a metabolic CO2 load that is readily countered with proportionate increase in ventilation without CO2 retention. Isocapnia from rest to exercise is maintained by the controller with the exercise ventilatory response being well adjusted for corresponding decrease in anatomical VD/VT, resulting in a small positive Y‐intercept in the ventilation vs. metabolic CO2 output relationship (Whipp's law). Remarkably, patients with congestive heart failure compensate for their abnormally large alveolar VD/VT with augmented ventilation, maintaining isocapnia at rest and during exercise without CO2 retention despite their decreased exercise tolerance. Thus, the control law governing isocapnic exercise ventilatory response is not merely determined by metabolic CO2 output per se but is responsive to an apparent (real‐feel) metabolic CO2 load that also accounts for the adverse effect of physiological VD/VT on pulmonary CO2 elimination. (Supported by HL067966 and RR028241)