William Sheel

Professor

Relevant Degree Programs

 

Postdoctoral Fellows

  • Bruno Archiza (Physiology, Respiratory System, Cardiovascular System)

Graduate Student Supervision

Doctoral Student Supervision (Jan 2008 - May 2019)
Sex differences in diaphragmatic fatigue (2018)

Purpose: The purpose of the thesis was to: 1) establish the reliability of cervical magnetic stimulation and chest wall surface EMG in the assessment of the diaphragmatic compound muscle action potential (CMAP) in healthy men and women (Study #1, Chapter 3), and 2) explore sex-based differences in the mechanisms and consequences of diaphragmatic fatigue (DF), specifically, 2a) the cardiovascular response to inspiratory resistance (Study #2, Chapter 4), and 2b) the effect of DF on subsequent exercise performance (Study #3, Chapter 5).Methods: Diaphragmatic fatigue was assessed in healthy men and women by measuring transdiaphragmatic twitch pressure using cervical magnetic stimulation. Surface electrodes were placed on the left and right hemi-diaphragm. Inspiratory pressure-threshold loading (PTL) was used to induce DF at rest, whilst a host of cardiovascular variables were measured (including: heart rate [HR], mean arterial [MAP] and low-frequency systolic blood pressure variability [LFSBP]). A time-to-exhaustion cycle test was performed with and without the induction of DF.Results: All CMAP characteristics demonstrated high reproducibility within and between experimental sessions. At PTL task failure, the degree of DF was not different between sexes (~23%); however, time to task failure was longer in women than men (27 vs. 16 min). Furthermore, women exhibited less of an increase in HR (13 vs. 19 bpm) and MAP (10 vs. 14 mmHg), and significantly lower LFSBP (23 vs. 34 mmHg²) during PTL compared to men. Prior-induced DF negatively and equally affected subsequent exercise performance in men and women (~15%). Conclusions: Cervical magnetic stimulation is a reliable means to evaluate phrenic nerve conduction in healthy men and women. The female diaphragm is highly fatigue resistant, leading to an attenuation of the inspiratory muscle metaboreflex (i.e. cardiovascular consequences of DF). Yet, DF impairs exercise independent of sex.

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Sex-differences in respiratory mechanics during exercise in healthy aging (2018)

Purpose: Three studies were performed in order to comprehensively examine the combined effects of healthy aging and biological sex on respiratory mechanics and the perception of dyspnea during exercise in healthy adults.Methods: Study #1 (Chapter 2) investigated the mechanical ventilatory and sensory responses to incremental exercise in a group of younger men and women (20-30 years old), and older men and women (60-80 years old). Study #2 (Chapter 3) examined inspiratory muscle recruitment patterns during incremental exercise in a group of younger men and women (20-30 years old), and older men and women (60-80 years old). Study #3 (Chapter 4) assessed whether experimentally manipulating the magnitude of mechanical ventilatory constraint during moderate-intensity exercise would alter the perception of dyspnea in a group of older men and women.Conclusions: Healthy aging and biological sex independently increase the magnitude of ventilatory constraint during exercise in healthy adults. Specifically, older individuals and women have a higher work of breathing for a given minute ventilation, and a higher propensity towards expiratory flow limitation during exercise than men and younger individuals, respectively. Additionally, older women have a higher perception of dyspnea during exercise than older men, which could be explained by the combined effects of age and sex on mechanical ventilatory constraint during exercise (Study #1). Healthy aging and biological sex also independently affect the pattern of inspiratory muscle recruitment during exercise, where older individuals and women rely on extra-diaphragmatic inspiratory muscles to a greater extent than older individuals and women, respectively (Study #2). Despite these differences in respiratory mechanics, acutely manipulating the magnitude of mechanical ventilatory constraint during moderate-intensity exercise did not have an effect of the perception of dyspnea (Study #3). Collectively, the results of this thesis suggest that sex-differences in respiratory mechanics during exercise persist throughout the healthy aging process, but do not contribute to the increased sensations of dyspnea observed in healthy older women relative to healthy older men.

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Sex differences in the integrated response to high respiratory muscle work during exercise (2017)

Purpose. The purpose of this thesis was to investigate sex differences in the integrated response to high respiratory muscle work during exercise. To accomplish this, I developed two novel methodologies (Chapters 2 & 4) in order to answer two subsequent research questions (Chapters 3 & 5).Methods. Chapter 2: Using computer software coupled with physiological measurements, I measured the oxygen cost of exercise hyperpnea in healthy subjects. Chapter 3: Healthy men and women performed voluntary hyperpnea while the oxygen cost of breathing was determined. The absolute and relative oxygen cost of breathing was compared between the sexes at different absolute and relative ventilation.Chapter 4: Using readily available components, I developed a proportional assist ventilator that could operate during all exercise intensities.Chapter 5: Healthy men and women completed three time-to-exhaustion (TTE) tests and quadriceps muscle fatigue was measured after each. The first TTE served as a control and during the 2nd and 3rd either a hyperoxic mixture was inspired or the work of breathing was lowered.Conclusion The oxygen cost of breathing can be consistently and reproducibly measured in healthy women when the work of breathing during exercise is precisely matched (Chapter 2). At ventilations above ~55 l min-¹, women have a greater oxygen cost of exercise hyperpnea. During intense exercise, the oxygen uptake of the respiratory muscles in women represents a greater fraction of total oxygen uptake (Chapter 3). A proportional assist ventilator can reduce the work of breathing to
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Expiratory time constant heterogeneity in experimental acute respiratory distress syndrome (2016)

Purpose This thesis evaluated regional heterogeneity of pulmonary mechanical values within models of lung injury. To this end four separate studies were completed. I evaluated regional expiratory time constant (τE) heterogeneity and tissue strain (ε) in a lung model using functional respiratory imaging (FRI) (Study 1, Chapter 2), and developed an in vivo porcine model of lung injury (Study 2, Chapter 3). This model was used to assess changes in τE due to manipulations of respiratory gas density (Study 3, Chapter 4) and mechanical ventilation parameters (Study 4, Chapter 5). MethodsStudy 1: Using computerized tomography (CT) images we generated 3-dimensional lung models. These were used calculated global and regional values for resistance, elastance, ε and τE under three different airway pressure conditions. Study 2: Experimental lung injury was induced in 11female Yorkshire X pigs. Necropsy, light and electron microscopy of lung was performed.Study 3: I utilized a multi-compartment model to describe the effects of changes in tidal volume (VT) and positive end-expiratory pressure (PEEP) on lung emptying during passive deflation before and after experimental lung injury in 6 adult female Yorkshire X pigs. Expiratory time constants (τE) were determined by partitioning the expiratory flow-volume (V˙ V) curve into multiple discrete segments.Study 4: Tracheal pressure and flow were measured in 7 pigs before and after experimental lung injury. Gas density was altered by using helium-oxygen (He), sulfur hexafluoride-oxygen (SF6) and nitrogen-oxygen (N2) gas. ConclusionsFunctional respiratory imaging demonstrates regional variation in both ε and τE. These findings raise questions about the use of whole lung measures of ε and τE to guide clinical management of lung injury (Study 1). I developed a stable model of lung injury using SPA that replicates the light and electron microscopic findings seen in human ARDS (Study 2). A pragmatic strategy using changes in the pattern of expiration described by a multi-compartment model of τE reveals that alterations in and gas density (Study 3) as well as PEEP and VT (Study 4) change expiratory pulmonary mechanics. These observations lay the groundwork for future clinical studies in lung injured patients.

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Hypoxia and autonomic control (2012)

Humans have a remarkable ability to cope with and survive exposure to hypoxia. Some have suggested a benefit in certain physiological systems in response to such exposure. However, the physiological response to hypoxia is multifaceted and includes an orchestrated response from many autonomic mechanisms. Thus, the purpose of this thesis was to more fully understand the human autonomic response to hypoxia as an integrated unit. Furthermore, pathological models of hypoxia provide evidence that suggests hypoxia can result in an autonomic response that outlasts the hypoxic stimulus. However, the persistent effect of hypoxia is only evident in certain reflexes, although comorbidities that accompany a pathological model complicate interpretation. Therefore, employing a healthy human model with continued measurement of physiological measures in the post-hypoxia period provides a more complete understanding of the integrated human physiological response to hypoxia. This Doctoral thesis is comprised of four separate investigations, each focusing on autonomic control both during and following an acute hypoxic exposure. In the first study (Chapter 2), the microneurography technique was used to demonstrate that the chemoreflex plays an important role in persistent sympathoexcitation following acute isocapnic hypoxia. With the use of the spontaneous baroreflex analysis technique, the follow-up study (Chapter 3) implicated a resetting of the arterial baroreflex that works to permit the persistent sympathoexcitation. The focus of the third study (Chapter 4) was on cerebrovascular control during fluctuations in blood pressure via bolus injections of vasoactive drugs. There was an improvement in cerebral autoregulation to increases in blood pressure following acute isocapnic hypoxia. The final study (Chapter 5) considered the role of carbon dioxide on hypoxic cerebral autoregulation, and found an impairment in isocapnic hypoxia but no effect in poikilocapnic hypoxia. The findings from this series of studies demonstrate the acute and persistent effects of short-term hypoxia, and the integrated nature in which autonomic mechanisms orchestrate the human physiological response to hypoxia.

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Acclimatisation, de-acclimatisation and re-acclimatisation to hypoxia (2011)

No abstract available.

Respiratory mechanics and diaphragmatic fatigue during exercise in men and women (2010)

No abstract available.

Master's Student Supervision (2010 - 2018)
Does inspiratory resistive loading cause expiratory muscle fatigue? (2016)

Expiratory resistive loading (ERL) elicits inspiratory as well as expiratory muscle fatigue, suggesting parallel co-activation of the inspiratory muscles during expiration. It is unknown whether the expiratory muscles are similarly co-activated to the point of fatigue during inspiratory resistive loading (IRL). The purpose of this study was to determine whether IRL elicits expiratory as well as inspiratory muscle fatigue. Male subjects (n=10) underwent isocapnic IRL to task failure (60% maximal inspiratory pressure, 15 breaths/min, 0.7 inspiratory duty cycle). Abdominal and diaphragm contractile function was assessed at baseline and at 3, 15 and 30 min post-IRL by measuring gastric twitch pressure (Pga,tw) and transdiaphragmatic twitch pressure (Pdi,tw) in response to potentiated magnetic stimulation of the thoracic and phrenic nerves, respectively. Electromyographic activity of the diaphragm, rectus abdominis, and external oblique was monitored to ensure consistency of stimulation. Fatigue was defined as >15% reduction from baseline in Pga,tw or Pdi,tw. During IRL (mean ± SE; 11.9 ± 2.5 min), mean arterial pressure and heart rate increased in a time-dependent manner (13 mmHg and 50 beats/min for the final min, respectively). Pdi,tw was significantly lower than baseline (34.1 ± 3.2 cmH₂O) at 3 min (23.2 ± 1.9 cmH₂O, p
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Effects of heliox on respiratory mechanics and sensory responses during exercise in endurance-trained men and women (2012)

Mechanical ventilatory constraints have been shown to develop in healthy endurance-trained (ET) men, and both ET and untrained women due to structural and functional sex-based differences with respect to the pulmonary system. The purpose of this study was to compare the effects of unloading the respiratory system using a heliox (He-O₂) inspirate on expiratory flow limitation (EFL), the work of breathing (WOB), operational lung volumes and sensory responses (leg and breathing discomfort) between men and women. It was hypothesized that He-O₂ would reduce EFL, operational lung volumes, the WOB and sensory responses while increasing airflow rates, minute ventilation (V’E) and exercise performance. The aforementioned changes would occur to a greater extent in women and those developing EFL breathing room air (RA). Endurance trained men (n = 11) and women (n = 11) competitive cyclists completed two 5 km time trials (TT), breathing either RA or He-O₂. The maximum expiratory flow-volume (MEFV) curve method was used to determine EFL. An esophageal balloon catheter was used to measure the WOB as determined by transpulmonary pressure (the difference between esophageal and mouth pressures). Sensory responses were recorded throughout the TTs. Both sexes had a small (albeit non-significant) 2.3% improvement in power output breathing He-O₂. During the RA TT, 60% of women and 36% of men developed EFL. Heliox significantly increased the MEFV curve for both sexes however 40% of women and 45% of men still developed EFL. The magnitude of EFL was variable throughout both TT’s for all subjects due to alterations in end expired lung volume and expiratory flow rates, as subjects utilized the He-O₂ induced enhanced ventilatory reserve. Despite significantly lower V’E, women had similar WOB and operational lung volumes as men. Sensory responses were not affected by sex, inspirate, or presence of EFL. Collectively these findings suggest that EFL occurs to various extents throughout endurance exercise in both sexes and may limit endurance performance. Sex-based differences in pulmonary structure and function predispose women to mechanical ventilatory constraints breathing RA and increase women’s relative cost of breathing compared to men.

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Exercise-induced arterial hypoxemia in healthy young women; role of mechanical constraints to ventilation (2012)

Many young adult male athletes with a high maximal O₂ consumption (VO₂Max) show exercise-induced arterial hypoxemia (EIAH). In women, EIAH may occur at submaximal exercise intensities and at lower fitness levels, but this is controversial. Greater EIAH in women may be attributed to their increased mechanical constraints to ventilation owing to smaller airway diameters. Accordingly, the purpose of this study was to characterize EIAH, gas exchange and respiratory mechanics during exercise in young healthy women. Subjects (n=31, VO₂Max =48±1, range 28-62 mL/kg/min) completed a step-wise maximal test on a treadmill. A 3-stage constant load exercise test was also completed where the inspired gas was switched between room air and heliox (21% O₂: 79% He). Arterial blood gases (PaO₂, PaCO₂, pH), corrected for esophageal temperature, and oxyhemoglobin saturation (SaO₂) were measured at rest and during the last 30 s of each exercise stage. The work of breathing (WOB) was obtained using an esophageal balloon-tipped catheter. Expiratory flow limitation (EFL) was determined by superimposing tidal flow-volume loops on the maximum expiratory flow-volume curve. Twenty of the 31 women developed some degree of EIAH with a nadir PaO₂ and SaO₂ ranging from 58-103 mmHg and 87-98%; respectively. Subjects with EIAH were fitter (VO₂Max 51±1 vs. 42±2 mL/kg/min), had a greater VEMax (91±3 vs. 77±4 L/min) and had an increased resistive WOB (30±2 vs. 19±1 cmH₂O/breath); for the EIAH and non-EIAH groups respectively (P
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The effect of consistent practice of yogic breathing exercises on the human cardiorespiratory system (2012)

Yogic breathing exercises (YBE) are complex breathing patterns that can include hyperventilation, hypoventilation, and apnea. Some YBE can significantly alter blood gases and result in hypoxic hypercapnia. The consequence of consistent practice of these breathing exercises is unknown. Thus, the purpose of this Master’s thesis was to quantify the cardiovascular, respiratory, and cerebrovascular effects of two common YBE: bhastrika and chaturbhuj; and, to determine the effect of their consistent practice on chemosensitivity. The first study was cross-sectional and compared experienced yogic breathers (YB) with matched controls in the above categories. It determined three things. First, bhastrika and chaturbhuj result in significant hypoxic hypercapnia. Second, the increase in blood pressure during their practice was higher in experienced yogic breathers. Third, experienced YB had reduced chemosensitivity compared to controls. The second was a controlled, longitudinal training study where experimental subjects practiced yogic breathing exercises for 6 weeks. This study had three major findings. First, after 6 weeks of training, bhastrika and chaturbhuj produced hypercapnia and mild hypoxia. Second, chaturbhuj resulted in cyclic oscillation of cardiovascular variables including blood pressure, heart rate, stroke volume, and cerebral blood flow velocity with inspiration and expiration. Third, post intervention there was no change in chemosensitivity measures. The findings from these two studies demonstrate that YBE significantly alter end-tidal gases, resulting in complex oscillations of cardiovascular and cerebrovascular variables, and if practiced for the long term, may reduce chemosensitivity.

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The influence of fitness level on the appearance of intrapulmonary arteriovenous shunting in healthy women (2010)

It was hypothesized that intrapulmonary arteriovenous shunts would be recruited at lower exercise intensities in highly trained individuals, compared to untrained and moderately trained individuals. Twenty-four women with normal lung and cardiac function, completed a maximal exercise test on a semi-supine cycle ergometer, while agitated saline contrast echocardiography was performed. Subjects were considered either untrained (VO₂peak 45 ml/kg/min), as determined by their performance on the exercise test. One subject did not shunt, four subjects demonstrated shunt pre-exercise, and eleven subjects demonstrated shunt in stage one of exercise. Twenty subjects continued to shunt immediately post-exercise, and seventeen subjects continued to shunt three minutes post exercise. These findings contrast with other studies in the upright cycling position, indicating an effect of body position. Percent of VO₂peak at shunt onset was not different between the groups, indicating no influence of training status. Cardiac output was not different between groups, potentially due to the inability of subjects to reach their true maximum on the exercise test. Peripheral oxygen saturation did not drop significantly during exercise and there was no difference in the lowest value reached by each group, indicating no limitations to pulmonary gas exchange.

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The muscle metaboreflex during exercise in chronic obstructive pulmonary disease (2010)

Chronic obstructive pulmonary disease (COPD) is characterised by deteriorating lung and airway function. Altered peripheral skeletal muscle properties, favouring glycolytic metabolism, are also well-documented in this population. Skeletal muscle properties such as those found in COPD patients may have significant effects on the magnitude of the muscle metaboreflex. Hypotheses: It was hypothesized that the muscle metaboreflex would be magnified in people with COPD compared to healthy controls, and that disease severity and exercise capacity would be correlated with the magnitude of the muscle metaboreflex. Methods: Eleven people with mild-to-severe COPD (FEV₁.₀ = 56.3 ± 7.4% predicted) and 11 age- and gender- matched controls performed isometric handgrip exercise (IHG) for 2.5 minutes, at 35% MVC, followed by 2 minutes of post-exercise circulatory occlusion (PECO). Hemodynamic changes were measured throughout the protocol to assess the magnitude of the metaboreflex. Participants also performed a progressive cycle test to volitional exhaustion. Results: Heart rate, mean arterial pressure (MAP), leg blood flow and leg vascular resistance responses were similar between the COPD group and controls throughout IHG and PECO (% change from baseline) (p > 0.05). Heart rate was highest at minute 2.5 of IHG (COPD 18 ± 4%, control 18 ± 3%) and returned to baseline during PECO, while MAP peaked at minute 2.5 of IHG (COPD 29 ± 5%, control 30 ± 3%) and remained elevated throughout PECO (COPD 25 ± 3%, control 21 ± 2%). Total peripheral resistance rose more in the COPD group throughout the protocol and approached significance at minute 2 of PECO (COPD 39 ± 9, control 18 ± 4%, p = 0.09). Cardiac output remained significantly higher throughout IHG and PECO in the control group (IHG 2.5 min: COPD 0.08 ± 7, control 17 ± 4%, p = 0.01). There was no association between disease severity (r = -0.22, p = 0.32) or exercise capacity (r = -0.02, p=0.92) and the magnitude of the muscle metaboreflex. Conclusions: The muscle metaboreflex is preserved in people with COPD. The mechanisms responsible remain unclear, however, unchanged upper limb skeletal muscle properties and desensitization of peripheral afferents to metabolites are plausible explanations.

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