William Sheel

The pathophysiological hallmark of Chronic Obstructive Pulmonary Disease (COPD) is dynamic hyperinflation and progressive impairment of ventilatory mechanics with exercise and contributes to intolerable perceptions of dyspnea. Patients with the most deteriorated health status may be candidates for lung transplantation. While lung mechanics generally improve post-transplant, affective and sensory perceptions of exertional dyspnea vary. PURPOSE: The purpose of this thesis was to compare ratings of dyspnea with lung and chest wall mechanics in COPD patients pre- and post-bilateral lung transplantation during incremental exercise to exhaustion and steady-state exercise breathing a helium-hyperoxia gas mixture. METHODS: Two older males (n=2) and one older female (n=1) between the ages of 60-70 waitlisted for transplantation participated in this study. All three subjects were GOLD stage IV COPD, defined as “very severe” with an FEV1
View record

The magnitude of exercise-induced diaphragmatic fatigue (EIDF) is similar in males irrespective of aerobic fitness. When compared to aerobically fit males, aerobically fit females appear less susceptible to EIDF. We hypothesized that chronic endurance training and regular exposure to high levels of exercise hyperpnea may confer EIDF resistance in aerobically fit females when compared to healthy females with average aerobic fitness. Healthy females (25 ± 4 years) performed graded cycle exercise to exhaustion to characterize aerobic fitness and were assigned into a highly-aerobically fit (Hi-Fit) or averagely-aerobically fit (Avg-Fit) group (Hi-Fit: n = 9, V̇O₂max = 56.1 ± 3.4 mL/kg/min; Avg-Fit: n = 9, V̇O₂max = 35.7 ± 4.9, p
View record

Early mobilization (EM) has been an increasingly recognized tool in the intensive care unit (ICU) for critically ill patients. Advances in critical care medicine has led to the growth of the cohort of patients termed ‘chronically critically ill’. These patients successfully stabilize from acute critical illness, however due to deterioration of physical and/or cognitive function become dependent on full time hospital care. ICU acquired weakness (ICUAW) is a spectrum disease characterized by symmetrical physical and/or cognitive impairments developed while admitted to an ICU. The development of ICUAW is a contributing factor that leads to chronic critical illness. EM has been proposed as a tool that can be used to prevent or slow down the onset of ICUAW. PURPOSE: The purpose of this thesis was to describe and quantify the rehabilitation practices and the cardiopulmonary trends in critically ill sepsis patients in the Vancouver General Hospital’s ICU. METHODS: Patients (n = 21) who met the inclusion and exclusion criteria were observed during a four-week period, Monday to Friday. The chart notes were used for Saturdays and Sundays. Daily cardiopulmonary vitals (e.g. heart rate (HR), blood pressure (BP), respiratory rate, peripheral oxygen saturation etc.) were taken at three time points and the chart notes were used to record test results. Additionally, physiotherapy sessions were observed and described. RESULTS: Norepinephrine had a decreased median dose during EM compared to prophylactic management in the released to ward outcome group. Sequential Organ Failure Assessment (SOFA) score was significantly different between patients who achieved a mobility score of 0 compared to ≥ 3 (p = 0.014). Sitting on the edge of the bed (EOB) elicited a HR and BP response suggestive of exercise in some patients. Lastly, the cardiopulmonary trends were consistent with what was expected. CONCLUSION: Norepinephrine dose and SOFA score may independently be able to help predict the mobility score a patient is likely to achieve during physiotherapy. The HR and MAP response observed during EOB in some patients participating in EM, presented a trend suggestive of exercise and warrants further investigation.

View record

The pulmonary system can maintain arterial blood gas homeostasis during exercise in healthy, young adults. However, some endurance athletes demonstrate a significant reduction in arterial oxygenation during exercise, a phenomenon termed exercise-induced arterial hypoxemia (EIAH). EIAH has been previously observed in young adults, and male masters athletes but there are no reports of gas exchange impairment in female masters athletes. It was hypothesized the majority of female masters athletes will develop EIAH during submaximal, near maximal, and maximal treadmill exercise. Pulmonary function was assessed followed by an incremental exercise test to determine maximal O2 uptake (V̇O2max). Participants were instrumented with a radial arterial catheter, an oesophageal balloon-tipped catheter, and temperature probe. Arterial samples were drawn while participants exercised at 60-70, 75, 90-95, and 100% V̇O2max for 2-4 minutes. Participants (n=6, 48-57 years) had an average V̇O2max of 47±2 ml/kg/min (range 40-55 ml/kg/min, 135-186% predicted). During submaximal, near maximal, and maximal exercise the arterial partial pressure of O2 (PaO2) decreased from rest by 14±2 mmHg (range 6-21), 13±4 (range -6-24), and 11±7 mmHg (range -7-21), respectively. The arterial partial pressure of CO2 (PaCO2) decreased from rest by 1.8±1 mmHg (range -2-6), 4±1 mmHg (range 0.3- 8), and 5±2 mmHg (range 2-5) at submaximal, near maximal, and maximal exercise, respectively. There was a reduction in oxyhemoglobin saturation 2.5± 0.3% (range 1.9-3.4) and arterial O2 content 1.2± 0.2 mL O2/100 mL of blood (range 0.7-1.8) at all intensities. Participants with a minimal change to PaCO2 tended to have a greater reduction in PaO2 (r = -0.85, R2 = 0.73, p
View record

The muscle metaboreflex is a cardiovascular control mechanism that contributes to the reflex increase in mean arterial pressure (MAP) and blood flow redistribution during exercise, to meet metabolic demands. The MAP response to metaboreflex activation is attenuated in females compared to males, during both limb and respiratory muscle work. Whether this sex-based difference is similar in magnitude across muscle groups is currently not well-understood. PURPOSE: The purpose of this thesis was to compare sex-based differences in the pressure response to limb and inspiratory metaboreflex activation, during relative and absolute workloads. METHODS: Seventeen healthy participants (n=9 males, n=8 females) completed two experimental visits; the first visit included pulmonary function tests, forearm volume and circumference measurements, and two bouts of exercise. The second day mimicked the first, except with no pulmonary function measurements. The exercise performed on both days were acute bouts of intermittent handgrip exercise (IHE) and pressure threshold loading (PTL) to volitional exhaustion, performed in a randomized order, and separated by 30-min of rest. PTL is a resistive breathing task that requires participants to generate large inspiratory pressures to overcome a threshold load, and attain unimpeded breathing. Participants exercised at a predetermined relative (R) or absolute (A) workload, and cardiopulmonary measurements were recorded continuously throughout. RESULTS: A time-dependent rise in MAP was observed in all participants, regardless of sex, muscle, or workload (p
View record

INTRODUCTION: Pediatric solid organ transplant (SOT) recipients report lower physical activity levels, exercise capacity, muscular strength, and quality of life than their healthy peers. Opportunities for structured recreational activity are limited for this population. Virtual exercise programs may reduce barriers to exercise, allow better access to specialized care, and cost less than traditional exercise rehabilitation programs. The aim of this study was to implement an 8-week virtual exercise program for pediatric SOT recipients. METHODS: A circuit-based training program with a primary focus on strength was designed by a clinical exercise physiologist (AD). All participants completed a treadmill exercise stress test prior to starting the exercise program. Self-report surveys were used to assess quality of life (Pediatric Quality of Life Inventory, PedsQL), fatigue (Pediatric Quality of Life Multidimensional Fatigue Scale, PedsQL-Fatigue), and physical activity (Physical Activity Questionnaire for Children and Adolescents, PAQ) at baseline and at completion of the program. The strength subtest of the Bruininks-Oseretsky Test of Motor Proficiency (2nd Edition) was administered virtually pre- and post-intervention. Exercise classes were conducted via Zoom, thrice weekly for 30 minutes. Weekly engagement with the study team was provided through a web-based text messaging platform (WelTel Inc., Vancouver, BC). Participants who could not attend a class were sent a recorded link of the class via email. RESULTS: Prior to the intervention, the median z-score for strength was -1.00 (-1.65 - -0.60). After the exercise intervention, strength scores improved to a z-score of -0.20 (-1.30 - 0.40); p=0.007. There were no changes in z-scores for the PAQ (-0.53 (-1.60 - -0.01) vs. -0.28 (-1.78 – 0.21) p=0.959, PedsQL -0.83 (-1.79 - -0.02) vs. -0.81 (-1.80 - -0.20); p=0.441, or PedsQL Fatigue [-0.75 (-1.90 - -0.08) vs. -0.74 (-1.49 - -0.16), p=0.314].CONCLUSION: Results showed that the delivery of this program was successful amongst participants. Increases in strength were seen following the 8-week exercise program with no changes in total quality of life, daily physical activity levels, and fatigue. These results suggest that a virtual exercise program may be used in future studies involving pediatric SOT patients to promote exercise.

View record

The mechanisms and sites that contribute to skeletal muscle fatigue vary depending on the specifications of the task, oxygen delivery, and fibre type composition. Due to anatomic and physiologic differences, men and women can have altered responses to a similar muscular fatiguing stimulus. The aerobic diaphragm muscle may exhibit neural protection under cases of potentially high fatigue, with a higher inhibition at the periphery. Hypoxia exacerbates key factors in diaphragm fatigue development, that may vary on the basis of sex. PURPOSE: The purpose of this thesis is to compare diaphragm fatigue between men and women under conditions of high-intensity exercise in normoxia and acute hypoxia. METHODS: Twenty healthy participants (n=10 men) came to the lab on three occasions, the first day included pulmonary characterization and a maximal graded exercise test. The final two trial days consisted of randomized exercise in a normoxic or a hypoxic condition (FIO₂ =0.21, 0.15, respectively). Exercise consisted of cycling at ~85% V̇O₂max until exhaustion; diaphragm force production was assessed via cervical magnetic stimulation pre- and post-exercise, and into recovery. RESULTS: There were no significant differences in the degree of diaphragm fatigue regardless of sex or FIO₂. Time-to-failure was significantly shorter in hypoxia for both groups (men: p = 0.016, women: p
View record

The diaphragm is the largest contributing muscle in a spontaneous breath. Classically, when failure in this muscle occurs, mechanical ventilation is implemented to reduce acute respiratory failure. The proportional assist ventilator (PAV) is a type of mechanical ventilator that can maintain gas homeostasis in dynamic exercise. However, PAV’s effect on the diaphragm, accessory respiratory muscles, and effectiveness during lower intensity exercise is still unclear. PURPOSE: To investigate the diaphragm electrical activity during low exercise intensity (10% below gas exchange threshold (GET)) while reducing the work of breathing via a PAV. METHODS: 8 participants (n = 4 male, n = 4 female; 26.8 ± 1 years) completed two days of testing. On day one, subjects performed a maximal VO2 exercise test on a cycle ergometer. On day 2, subjects cycled at 10% below GET while alternating breathing on the PAV and spontaneously. Electromyography of the diaphragm (EMGdi), scalenes (EMGSCA), and sternocleidomastoids (EMGSCM), work of breathing (WOB), pressure time product of the esophagus (PTPes), diaphragm (PTPdi) and gastric (PTPga) were measured throughout the experimental protocol. RESULTS: WOB was lower while breathing on the PAV during medium (p
View record

Competitive swimmers have high rates of exercise induced bronchoconstriction (EIB), which may be associated with repeated exposure to chlorinated pool water. The eucapnic voluntary hyperpnea (EVH) test is often used in a laboratory setting to provoke a reduction in lung function associated with EIB. Swimmers however, experience EIB symptoms in warm, humid and chlorinated environments. The relationship between EVH testing conditions and the development of EIB from swim exercise is unclear. PURPOSE: To compare the provoking effects of inspired air and high-intensity exercise in inducing EIB in swimmers to laboratory-based EVH method. METHODS: 15 collegiate swimmers (n=5 male, n=10 female; 21±2 years) completed three days of testing in random order. On day one, subjects performed an EVH test in a laboratory (EVH-L). On a separate day, swimmers performed a modified EVH test, while breathing chlorinated pool air (EVH-Cl). On a third day subjects completed a swimming challenge (Swim), performing consecutive 200 and 400 m freestyle efforts at 85% of their season’s best time (average achieved 200 and 400 m time; 2:18.52±7.79 and 4:55.22±20.38, respectively) and age-predicted heart rate maximum. Lung function was measured at baseline, as well as 3-, 5-, 10-, 15-, and 20-minutes following EVH testing and swim exercise. RESULTS: EVH-L elicited a -9.7±6.4 % fall compared to the EVH-Cl test, -6.6±9.2 % (p>0.05) and Swim, -3.0±7.5 % (p>0.05). A significant correlation in FEV1 fall index between EVH-L vs. EVH-Cl (r =0.78, p0.05) and EVH-CL vs. Swim (r =0.50, p>0.05). A greater reduction in forced expired flow between 25 and 75 % lung volume (FEF25-75) was induced by the EVH-L (-16.6±8.7 %) compared to the EVH-Cl (-8.2±14.9 %) (p>0.05) and Swim test (-1.3±15.6 %) (p
View record

Whether the large lungs of competitive swimmers result from intensive swim training or genetic endowment has been widely debated. Given that peak growth velocities for the lungs occur during puberty, this longitudinal study aimed to determine if competitive swimming during puberty affected lung development. Female swimmers (n=11) and healthy controls (n=10) aged 11-14 years old were assessed before and after one competitive swimming season. Pulmonary function testing included lung volumes, spirometry, diffusion capacity (DL,CO), and maximal inspiratory (PIMAX) and expiratory (PEMAX) pressures. Ventilatory constraints, including end-expiratory lung volume (EELV), expiratory flow limitation (EFL), and utilization of ventilatory capacity (V̇E/V̇ECAP), were assessed during an incremental cycling test. Despite being of similar age (p=0.10), maturational development (p=0.27), and height (p=0.38) as controls, swimmers had a larger total lung capacity (p0.05). Pubertal female swimmers already had larger lung capacities, higher flows, and greater indices of respiratory muscle strength, but similar ventilatory constraints while cycling. One competitive swimming season did not further accentuate this enhanced function or alter exercise ventilatory mechanics, suggesting that competitive swimming during puberty did not affect lung development.

View record

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
View record

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.

View record

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
View record

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.

View record

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.

View record

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.

View record