Early Aerobic Exercise Intervention After Stroke: Improving Aerobic and Walking Capacity
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Early Aerobic Exercise Intervention After Stroke: Improving Aerobic and Walking Capacity by Jake Jangjin Yoon A thesis submitted in conformity with the requirements for the degree of Master of Science Graduate Department of Rehabilitation Science University of Toronto © Jake Jang Jin Yoon 2009
Abstract Early Aerobic Exercise Intervention After Stroke: Improving Aerobic and Walking Capacity Jake Jang Jin Yoon Advisor: Master of Science, 2009 Dr. Dina Brooks Graduate Department of Rehabilitation Science University of Toronto The benefits of brief-duration, early exercise programs in stroke have been shown, but the effects of longer-duration aerobic training early after stroke have not been examined. The purpose of this study was to determine the effects of an early aerobic exercise program that extended beyond inpatient into outpatient rehabilitation on aerobic capacity, walking parameters (walking distance, speed, and symmetry), health-related quality of life, and balance. Patients in the subacute phase after stroke (n = 15) with mild to moderate impairment received aerobic exercise in addition to conventional rehabilitation. The study participants demonstrated significant improvement in aerobic and walking capacity, peak work rate, quality of life, balance, and gait velocity from baseline to midpoint. However, no difference was found between midpoint and final. This early aerobic exercise program following stroke significantly improved aerobic capacity, walking ability, quality of life and balance during the inpatient period although no further improvement was observed during the outpatient period. ii
Acknowledgements First of all, I would like to thank my supervisor, Dr. Dina Brooks, for her ongoing support throughout my study. My thesis would not have been possible to complete without your guidance, and you are one of the most influential people who made my graduate experience fun and memorable. I cannot express my gratitude enough to you and I feel extremely lucky to have you as my supervisor. I would also like to thank Dr. Bill McIlroy for his guidance and patience. He has guided me through my graduate studies along with Dina when I felt overwhelmed with many questions. He is also one of the reasons why my graduate experience has been such a enjoyable experience. You have been such a great leader and a great mentor, and it has been my honour to work with you. I am grateful to Dr. Scott Thomas for his guidance and feedback. You have taught me how to think critically and made me become better at research. I would like to thank everyone at the Mobility Team for their support, especially Hannah Cheung, Sanjay Prajapati, Bimal Lakhani, and Ada Tang for their wisdom and laughter. I thank everyone at Toronto Rehab who made this work possible including Lou Biasin, Janice Komar, Jackie Lymburner, Chris Peppiatt, Dr. Mark Bayley, Dr. Denise Richardson, Dr. Lisa Becker, and all the study participants. Finally, I would like to thank my family and friends for their unconditional support and love. I truly believe that I would not have accomplished many of my goals if I did not have their support and belief in my ability. You are the source of my inspiration and drive to excel in what I do. Thank you. I am extremely fortunate to be surrounded by many inspirational and supportive people, and I sincerely apologize to you if I have missed you here. But, I am truly grateful to all of you who have guided and supported me. iii
Table of Contents Abstract ii Acknowledgements iii Table of Contents iv List of Tables vi List of Figures vii Abbreviations viii 1.0 Introduction 1 2.0 Background 5 2.1 Epidemiology of Stroke 5 2.2 Stroke Risk Factors 5 2.3 Impairments and Disabilities Following Stroke 7 2.3.1 Walking Capacity 9 2.3.2 Aerobic Capacity 11 2.4 Aerobic Training in Chronic Stroke Population 13 2.5 Aerobic Training in Subacute Stroke Population 20 2.6 Aerobic Exercise and Conventional Stroke Rehabilitation 24 2.7 Research Rationale and Objectives 24 2.8 Hypothesis 25 3.0 Methods 26 3.1 Participants 26 3.2 Measurements 26 3.3 Training Protocol 31 3.4 Data Analysis 32 4.0 Results 33 4.1 Demographics and Training Parameters 33 iv
4.2 Aerobic Capacity 37 4.2.1 Peak Work Rate (WRpeak) 38 4.2.2 Peak Heart Rate (HRpeak) 40 4.3 Six-Minute Walk Test 41 4.4 Secondary measurements 45 5.0 Discussion 54 5.1 Clinical Implications 58 5.2 Limitations 58 5.3 Future Directions 59 6.0 Conclusion 61 7.0 References 62 8.0 Appendices 73 8.1 Chedoke-McMaster Assessment Scale 73 8.2 VO2peak Assessment Form 75 8.3 Modified Borg Rating of Perceived Exertion Scale 76 8.4 Stroke Impact Scale 77 8.5 Berg Balance Scale 83 v
List of Tables Table 1. Summary of literature: effects of aerobic training in chronic stroke 15 Table 2. Summary of literature: effects of aerobic training in sub-acute stroke 21 Table 3. Participant eligibility criteria 26 Table 4. Participant demographics at baseline 36 Table 5. Training parameters 36 Table 6. Gait symmetry values obtained during fast- and preferred-gait for all participants 50 Table 7. Gait symmetry values obtained during fast- and preferred-gait for participants with complete data 51 Table 8. Main outcome comparison between current and previous studies 52 Table 9. Patient characteristics from current and previous studies at baseline 53 vi
List of Figures Figure 1. Study timeline summary 27 Figure 2. Reason for exclusion 34 Figure 3. Flowchart depicting participants through each stage of the study 35 Figure 4. Baseline, midpoint and final values for VO2peak 37 Figure 5. Relationship between change in VO2 and number of training sessions 38 Figure 6. WRpeak obtained during max tests 39 Figure 7. Relationship between change in WR and number of training sessions 40 Figure 8. HRpeak obtained during max tests 41 Figure 9. Baseline, midpoint and final values for 6MWT with non-ambulatory participants (SA02, SA04, SA14, SA18, and SA25) given a score of 0m 42 Figure 10. Relationship between change in 6MWD and number of training sessions 43 Figure 11. Baseline, midpoint and final 6MWT values for participants excluding non-walkers at baseline 44 Figure 12. Relationship between change in 6MWD and number of training sessions excluding non-walkers 45 Figure 13. Scores for the SIS 46 Figure 14. Scores for the BBS 47 Figure 15. Baseline, midpoint and final gait velocity values for all participants 48 Figure 16. Baseline, midpoint and final gait velocity values for participants with complete data 49 Figure 17. Relationship between change in 6MWD and change in VO2peak 51 Figure 18. Comparison between current and previous study 53 vii
Abbreviations 6MWT Six-minute walk test ACSM American College of Sports Medicine ADL Activities of daily living ATP Adenosine triphosphate BBS Berg Balance Scale BP Blood pressure bpm Beats per minute CAD Coronary artery disease CMSA Chedoke McMaster Stroke Assessment DM Diabetes Mellitues ECG Electrocardiogram HR Heart rate HRpeak Peak heart rate HRR Heart rate reserve NIH National Institutes of Health Stroke Scale RER Respiratory exchange ratio RPE Rating of perceived exertion RPM Revolutions per minute SD Standard deviation SIS Stroke Impact Scale TM Treadmill TRI Toronto Rehabilitation Institute VO2 peak Peak oxygen consumption VO2 Oxygen consumption, oxygen uptake W Watts WR Work rate WRpeak Peak work rate viii
Chapter 1 1.0 Introduction Stroke is the leading cause of neurological disability in adult Canadians (Heart and Stroke Foundation of Canada, 2008), leaves many individuals post stroke with social isolation and reduced quality of life (Schepers, Visser-Meily, Ketelaar, & Lindeman, 2005), and puts a strain on the Canadian economy (Heart and Stroke Foundation of Canada, 2008). Every year, 35,000 – 50,000 Canadians suffer strokes, and there are approximately 300,000 individuals with stroke (Heart and Stroke Foundation of Canada, 2008). Unfortunately, these individuals have a 20% chance of having another stroke within 2 years of their first stroke (Heart and Stroke Foundation of Canada, 2008). Over the past decade, there has been a 30% increase in individuals with stroke worldwide, and this number may increase because of the combination of aging demographics, advances in medical care and improved stroke management (Patten, Lexell, & Brown, 2004). These individuals often experience interruptions in communication and cognition in addition to physical impairment, making it hard for them to integrate into the community (MacKay-Lyons & Howlett, 2005a). Hence, individuals post stroke often experience limited social participation and reduced quality of life (Jorgensen et al., 1995). Furthermore, the loss of individuals with stroke from the work force and their extended hospitalization following stroke has a large economic impact, costing the Canadian economy $2.7 billion a year (Heart and Stroke Foundation of Canada, 2008). For example, the average cost of acute care is about $27,000 per patient with stroke, and Canadians spend a total of 3 million days in hospital because of stroke (Heart and Stroke Foundation of Canada, 2008). To reduce the heavy economic burden on our economy, it is important to establish both effective and economic stroke programs which address stroke prevention and management. Aerobic exercise may be an effective way to manage and modify many risk factors of stroke and it may also be useful in effectively reducing stroke-related impairments since aerobic exercise has the potential to improve aerobic and walking capacity, prevent a cycle of inactivity, and 1
improve quality of life. However, aerobic exercise has not been adequately implemented in stroke rehabilitation, and further studies are needed to elucidate the effects of aerobic exercise, especially during the inpatient rehabilitation period. Several authors have demonstrated the beneficial effects of aerobic exercise in stroke recovery using various exercise modalities including treadmill (Macko et al., 2005; Pohl, Mehrholz, Ritschel, & Ruckriem, 2002; Teixeira-Salmela, Olney, Nadeau, & Brouwer, 1999), cycle ergometer (Lennon, Carey, Gaffney, Stephenson, & Blake, 2008), and recumbent cross trainer (Page, Levine, Teepen, & Hartman, 2008). Improvements following aerobic exercise have been observed in cardiorespiratory fitness (Rimmer, Riley, Creviston, & Nicola, 2000), walking distance (Ada, Dean, Hall, Bampton, & Crompton, 2003; Pang, Eng, Dawson, McKay, & Harris, 2005) and velocity (Ada et al., 2003; Pohl et al., 2002), quality of life (Teixeira-Salmela, Nadeau, Mcbride, & Olney, 2001), balance (Page et al., 2008), stride length (Pohl et al., 2002), muscle strength of affected lower limb (Pang et al., 2005), body composition (Rimmer et al., 2000), and flexibility (Rimmer et al., 2000). Exercise training also has the potential to prevent recurrent strokes by managing many stroke risk factors including hypertension (Pescatello et al., 2004), hyperlipidemia (Stone, Bilek, & Rosenbaum, 2005), obesity (Villareal et al., 2006), insulin resistance (Villareal et al., 2006), and inflammation (Dekker et al., 2007). Cardiovascular fitness and walking capacity were of particular interest in this study because they have been shown to be significantly impaired following stroke, possibly resulting in inactivity and low quality of life. Cardiorespiratory fitness is severely reduced early after stroke, falling to 50% to 70% that of age- and sex-matched values of sedentary individuals (Kelly, Kilbreath, Davis, Zeman, & Raymond, 2003; MacKay- Lyons & Makrides, 2002b; Mackay-Lyons & Makrides, 2004). For instance, individuals in the subacute phase after stroke often do not satisfy the minimum oxygen uptake (VO2) value of 15 ml/kg/min to meet the physiologic demands for independent living (MacKay-Lyons & Makrides, 2002b). Furthermore, these individuals require greater oxygen uptake at a given workload than healthy age-matched individuals possibly due to reduced mechanical efficiency in movement and the effects of spasticity 2
(Gordon et al., 2004). The debilitating combination of poor cardiovascular fitness and increased energy costs for hemiparetic gait can hinder individuals post stroke from being physically active, negatively affecting their performance of activities of daily living (ADL). Many individuals with stroke possess impaired gait which may lead to low quality of life. According to the Copenhagen Stroke Study, 64% of patients with stroke walk independently at the end of rehabilitation (Jørgensen, Nakayama, Raaschou, & Olsen, 1995). However, only 7% of patients with stroke may have sufficient capacity to walk outside their homes (Goldie, Matyas, & Evans, 1996). Low walking competency may be accounted for low aerobic capacity (Pang, Eng, & Dawson, 2005) and abnormal gait present in up to two-thirds of individuals with stroke (Teixeira-Salmela et al., 2001). These abnormal gait patterns can be caused by deficits in sensorimotor control following stroke, leading to inefficient mobility. Hence, impaired walking capacity must be addressed effectively following stroke because low walking capacity may limit social participation and reduce quality of life (Langhammer, Stanghelle, & Lindmark, 2008). Despite the fact that aerobic exercise has the potential to improve aerobic and walking capacity in stroke survivors, it has not been consistently implemented in conventional rehabilitation. Also, there are no clear evidence-based guidelines for prescribing aerobic exercise, especially to the subacute stroke population. The recovery of neuromuscular function has been the overall aim of stroke rehabilitation which emphasizes training to remediate balance, strength and coordination issues (Potempa et al., 1995). Recent findings suggest that conventional stroke rehabilitation does not provide aerobic exercise of an adequate intensity to reverse the profound physical deconditioning in individuals post stroke (MacKay-Lyons & Makrides, 2002a). Furthermore, a recent Cochrane review investigated the effects of aerobic training on stroke recovery by analyzing data from 12 randomized controlled trials. The authors concluded that there were few data available to guide clinical practice at present with regard to fitness training interventions after stroke and more research was needed to 3
explore the efficacy and feasibility of training, particularly soon after stroke (Saunders, Greig, Young, & Mead, 2004). To examine the efficacy and feasibility of early aerobic training, a previous study from our group exercised inpatients on a semi-recumbent cycle ergometer (3 sessions per week, 30 minutes per session) in addition to their inpatient rehabilitation (Tang, Sibley, Thomas, Bayley, Richardson, McIlroy, & Brooks, 2009). Upon completion of the study intervention, the Exercise group showed a trend towards greater improvements in aerobic and walking capacity, compared to the Control group. The authors suggested that the short training period during inpatient rehabilitation may have limited the extent of aerobic benefits and hypothesized that extending the training beyond inpatient rehabilitation would likely give rise to significant gains in aerobic and walking capacity. Therefore, the current study was conducted to determine the effects of aerobic exercise early after stroke on cardiovascular fitness, walking capacity, and various functional outcomes following stroke. 4
Chapter 2 2.0 Background 2.1 Epidemiology of Stroke Stroke is the fourth leading cause of death in Canada (Heart and Stroke Foundation of Canada, 2008). Approximately, 70% of the strokes occur in individuals over the age of 65, and the risk of stroke doubles each decade after 55 years old (Heart and Stroke Foundation of Canada, 2008). Also, over 50% of individuals post stroke under the age of 65 die within eight years (American Heart Association, 2002). Men have a greater risk of having a stroke than women, and 45% more women than men die from stroke in Canada (Heart and Stroke Foundation of Canada, 2008). The greater mortality in women is partially due to the fact that women live longer on average than men and stroke mortality increases with age (Heart and Stroke Foundation of Canada, 2008). It has been reported that about 70% of strokes are caused by cerebral ischemia, 27% by cerebral hemorrhage, and 3% by unknown reasons (Foulkes, Wolf, Price, Mohr, & Hier, 1988). According to the Heart and Stroke foundation of Canada, of every 100 people who have a stroke, 15 die, ten recover completely, 25 recover with a minor impairment or disability, 40 are left with a moderate to severe impairment, and ten are severely disabled and require long-term care (Heart and Stroke Foundation of Canada, 2008). Hence, it is imperative to recognize stroke risk factors and eliminate them appropriately if possible. 2.2 Stroke Risk Factors Some stroke risk factors are hereditary or caused by natural processes while others result from a person’s lifestyle (American Heart Association, 2002). Some of the risk factors that cannot be modified are age, heredity, race, and gender while controllable risk factors include high blood pressure, cigarette smoking, diabetes mellitus, cardiovascular disease, high blood cholesterol, poor diet, and physical inactivity 5
(American Heart Association, 2002). Many risk factors have been identified, and a few crucial ones from a study by Foulkes and colleagues (Foulkes et al., 1988) are listed as follows: • Age: Age is shown to be the single most important factor for stroke. The stroke rate after the age of 55 increases by a factor of more than two in both men and women for every 10 years. • Gender: Stroke occurs 1.25 times greater in men. However, because women live longer than men, women have a higher death rate from stroke. • Ethnicity: Blacks are about twice more likely to die of stroke than whites, and this mortality rate for blacks increases up to five times, compared to whites for the age group between 45 and 55. Asians, especially Chinese and Japanese, have a high stroke rate. • Heredity: An increased rate of stroke within families has long been documented, and potential reasons include a genetic tendency for stroke and its risk factors. • Hypertension: Hypertension is a major modifiable risk factor, and the level of hypertension is a good indicator for the risk of stroke. Both systolic and diastolic pressures are shown to be important for monitoring the risk of stroke. • Smoking: Smoking is an important modifiable risk factor for stroke and has been shown to increase the risk by 1.5. • Diabetes Mellitues (DM): People with diabetes mellitus and impaired glucose tolerance are more susceptible to atherosclerosis, and DM has been shown to be an independent risk factor for ischemic stroke with a risk range from 1.8 to 3.0. • Physical Inactivity: This factor has received increasing attention, and the beneficial effects of physical activity are potentially achieved by controlling various risk factors. Exercise training has been shown improve many other stroke risk factors in non-stroke population (Villareal et al., 2006), including hypertension (Pescatello et al., 2004), hyperlipidemia (Stone et al., 2005), obesity (Villareal et al., 2006), insulin resistance (Villareal et al., 2006), and inflammation (Dekker et al., 2007). Furthermore, epidemiological studies suggest that physical 6
activity is inversely associated with increased risk for stroke (Gordon et al., 2004). Individuals with stroke often have significant atherosclerotic lesions throughout their vascular system and are at a greater risk for, or already have, associated comorbid cardiovascular disease (Roth, 1993; Wolf, Clagett, Easton, Goldstein, Gorelick, Kelly- Hayes, Sacco, & Whisnant, 1999). In fact, atherosclerosis is one of the most common underlying causes of ischemic stroke, and it is not surprising that many of the important modifiable risk factors for coronary artery disease (CAD) are also stroke risk factors, including hypertension, abnormal blood lipids and lipoproteins, cigarette smoking, physical inactivity, obesity, and diabetes mellitus (Gordon et al., 2004; Pearson et al., 2002; Wolf, Clagett, Easton, Goldstein, Gorelick, Kelly-Hayes, Sacco, & Whisnant, 1999a). As many as 75% of individuals with stroke have cardiac disease and those who survive for many years following stroke are more likely to die from cardiac disease than from any other cause, including a second stroke (Roth, 1993). Evidence from clinical trials suggests that stroke can often be prevented (Sacco et al., 1997). Intensive management of risk factors can be expected to lessen the risk for atherothrombotic events in the coronary or peripheral arteries, reducing the risk of stroke and cardiac events (Gordon et al., 2004). The combination of management and modification of the risk factors through lifestyle interventions and appropriate pharmacological therapy is important for the prevention of stroke (Wolf, Clagett, Easton, Goldstein, Gorelick, Kelly-Hayes, Sacco, & Whisnant, 1999) Therefore, physical activity, which modifies many stroke risk factors, should be considered as one important element of a stroke prevention program. 2.3 Impairments and Disabilities Following Stroke The primary impairments due to upper motor neuron damage following stroke may include hemiplegia, incoordination, spasticity, balance disturbances, sensorimotor loss, and aphasia (Gordon et al., 2004). Many factors affect the degree of impairment 7
including physiological factors such as the mechanism, extent, and location of the vascular lesion (Patten et al., 2004). The secondary impairments often include disuse muscle atrophy, changes in muscle fiber type distribution and metabolism, and muscle fatigue (MacKay-Lyons & Howlett, 2005). Functional disabilities, on the other hand, are characterized by compromised abilities to perform ADL, such as making a bed and showering (Gordon et al., 2004). Impairments following stroke can contribute to the deconditioned state commonly observed in individuals with stroke. For example, hemiparesis can dramatically reduce the amount of muscle mass and the pool of motor units available during physical activity, thus decreasing the metabolically active tissue (Saunders et al., 2004). Moreover, a number of biological changes have been shown to occur in skeletal muscles and surrounding tissues following stroke, resulting in further disability and low fitness levels. Individuals post stroke have low levels of lean tissue mass which is an independent predictor of peak oxygen comsumption (VO2peak) and thus have an impaired ability to use oxygen (Ryan, Dobrovolny, Silver, Smith, & Macko, 2000). A deficit severity-dependent shift towards a fast-twitch muscle molecular phenotype in the paretic leg makes individuals post stroke more susceptible to fatigue and insulin resistant which may account for the high incidence of impaired glucose tolerance in this population (De Deyne, Hafer-Macko, Ivey, Ryan, & Macko, 2004; Ivey, Hafer-Macko, & Macko, 2008). Also, intramuscular area fat is 25% greater in the paretic thigh area than in the non-paretic thigh region (Ivey, Hafer-Macko, & Macko, 2008). Increased intramuscular fat has been related to insulin resistance and its complications, suggesting that these changes in body composition might impact metabolic health as well as fitness and function (Ryan, Dobrovolny, Silver, Smith, & Macko, 2000). Often, individuals post stroke are negatively affected not only by impairments in neuromuscular control, but also interruption in communication, continence, cognition, perception, and mental status (MacKay-Lyons & Howlett, 2005). There are many factors affecting disability of stroke survivors, and factors other than the loss of neuromuscular function should not be overlooked in order to explain the causes of disability. 8
Although many individuals post stroke continue to experience functional limitations, neurological impairments may only account for less than a third of stroke-induced disabilities (Roth et al., 1998). Other factors influencing disabilities include motivation, coping skills, cognition, pre- and post-stroke medical comorbidities, physical fitness level, effects of treatment, and the type and duration of rehabilitation training (Gordon et al., 2004). Various impairments and disabilities following stroke can create a debilitating cycle of further decreased physical activity and greater exercise intolerance, leading to secondary complications such as reduced cardiorespiratory fitness and muscle atrophy. For instance, even though over 60% of individuals with stroke achieve independent walking at the end of rehabilitation (Jørgensen et al., 1995), they still are faced with gait asymmetry (Patterson et al., 2008), increased energy expenditure during walking (Macko et al., 2001), reduced walking speed (Tang, Sibley, Thomas, Bayley, Richardson, McIlroy, & Brooks, 2009), and decreased walking distance (Patterson et al., 2007). These impairments in walking parameters may result in low physical activity, social isolation, and ultimately reduced quality of life. Thus, recovering walking capacity post stroke should be addressed effectively in stroke rehabilitation. 2.3.1 Walking Capacity Walking is a coordinated function which requires a highly integrated neural control system. Stroke often leads to long-term walking impairment by disrupting these neural control systems. To perform successful gait, individuals post stroke are required to maintain balance of the upper body over the hip joints, coordinate stance and swing phases of walking, and produce sufficient energy to propel the body forward with each step. Typical abnormal movement patterns include reduced knee flexion during swing and stance phase, knee hyperextension during stance, and excessive ankle plantar flexion during swing and/or stance (Pease, Bowyer, & Kadyan, 2005). Each of these movements has the potential negative effect of raising the energy expenditure for walking, thus making gait more difficult by disrupting the rhythmic motion and stability of walking. 9
One of the most functionally limiting impairments following a stroke may be a dramatic decrease in gait velocity (Pease et al., 2005). Walking velocity is influenced by step length and cadence, and a decrease in either or both of these parameters can result in decreased gait velocity (Pease et al., 2005). Individuals post stroke with gait impairments spend more time both during single-limb stance on the unaffected side and also during double-limb support, causing low gait velocity (Pease et al., 2005). This increased duration of single-limb stance on the unaffected side is due to a delay in initiation and a decrease in the speed of hip flexion during swing phase (Pease et al., 2005). Even though restoration of walking is a primary goal in stroke rehabilitation, many people with stroke continue to experience impaired gait which results in high energy costs. According to the Copenhagen Stroke Study, 64% of individuals post stroke walk independently at the end of rehabilitation, 14% walk with assistance, and 22% are unable to walk (Jørgensen et al., 1995). Initial walking is impaired in two-thirds of the stroke population (Teixeira-Salmela et al, 2001)), and abnormal gait patterns in individuals with stroke can be caused by deficits in sensorimotor control following stroke, leading to inefficient mobility. Also, the oxygen cost of walking is greater in hemiplegic patients compared to that of healthy subjects of comparable body weight (Gordon et al., 2004) which may discourage the patients from being physically active. Stroke can increase the energy cost of walking up to two times that of able-bodied persons by dramatically reducing the mechanical efficiency of walking (Macko et al., 2001). Because of the high energy cost associated with gait following stroke, reduced physical activity level is commonly observed in this population (Michael, Allen, & Macko, 2005). Furthermore, a recent study by Newman and colleague demonstrated an association between poor performance in long-distance walking and mortality and cardiovascular disease in older adults (Newman, Simonsick, & Naydeck, 2006). Therefore, restoration of gait is a crucial part of conventional stroke rehabilitation given its importance in the 10
performance of ADL, maintenance of independence, and reduction of other health problems associated with immobility and sedentary lifestyle. 2.3.2 Aerobic Capacity Aerobic capacity refers to the highest amount of oxygen consumed while performing large muscle, moderate-to-high intensity exercise for prolonged periods (American College of Sports Medicine, 2006). Aerobic capacity is often used interchangeably with cardiorespiratory fitness, cardiovascular fitness, and exercise capacity. Peak oxygen consumption (VO2peak) obtained from a maximal exercise test is the single most important measure of cardiorespiratory fitness (American College of Sports Medicine, 2006). It is important to maintain high levels of cardiorespiratory fitness because low levels of VO2peak are associated with increased risk of premature death from all causes; especially from cardiovascular disease (American College of Sports Medicine, 2006). There are many factors affecting VO2peak, including age, gender, heredity, and training. VO2peak decreases at least by 0.25mL/kg/min every year for men and women after the age of 25, and exercise capacity for women is typically 15% to 30% lower than that of men (MacKay-Lyons & Howlett, 2005). Heredity also plays a major role in VO2peak and may account for up to 50% of the variance between individuals (Wolfarth, 2001). Physical training can improve VO2peak at any age, and the American College of Sports Medicine (ACSM) recommends exercising at an intensity ranging from 40% to 85% of heart rate reserve (HRR) with a training duration of greater than 20 minutes for 3-5 days/week to increase VO2peak (American College of Sports Medicine, 2006). Cardiovascular fitness is significantly reduced early after stroke, falling to 50% to 70% of age- and sex-matched values of sedentary individuals (Kelly et al., 2003; MacKay- Lyons & Makrides, 2002; Mackay-Lyons & Makrides, 2004). According to the ACSM, for male individuals between the age of 50 and 59, a VO2peak for 90th percentile is 49.0 11
ml/kg/min and 10th percentile 29.9 ml/kg/min (American College of Sports Medicine, 2006). As for females with the same age range, a VO2peak for 90th percentile is 37.8 ml/kg/min and 10th percentile 21.9 ml/kg/min. VO2peak following stroke is often much lower than these values and has been reported to be as low as 8.3 ± 0.9 ml/kg/min (Teixeira da Cunha Filho et al., 2001). Unfortunately, the levels of VO2peak early after stroke are often lower than the minimum VO2 value of 15 ml/kg/min to meet the physiologic demands for independent living (MacKay-Lyons & Makrides, 2002). Low levels of VO2peak in individuals with stroke have been associated with reduced functional performance, often affecting the performance of ADL (Pang, Eng, Dawson, & Gylfadóttir, 2006). These individuals are required to work at a higher exercise intensity to complete the same functional activities, when compared with their fitter counterparts (Pang et al., 2006). Hence, cardiac and respiratory muscles are required to work harder, expending more energy, and this may lead to early exhaustion in people with low aerobic capacity. Furthermore, many individuals with stroke require greater oxygen uptake at a given workload than in healthy age-matched individuals possibly due to reduced mechanical efficiency in movement and the effects of spasticity (Gordon et al., 2004). Hence, the debilitating combination of poor cardiovascular fitness and increased energy costs for hemiparetic gait can hinder individuals post stroke from being physically active, negatively affecting their performance of ADL. Furthermore, reduced levels of VO2peak may increase the risk of various health-related conditions. Diminished cardiovascular fitness has been associated with an increased risk of various forms of cardiovascular disease (Pang et al., 2006), insulin resistance (Ivey, Hafer-Macko, & Macko, 2008), and osteoporosis in the chronic stroke population (Pang et al., 2006). Also, low aerobic capacity may be one of the strongest predictors of stroke, comparable with other important stroke risk factors (Kurl et al., 2003). Lee and Blair examined the association between cardiovascular fitness and stroke mortality following 16,878 healthy men with no history of previous stroke, aged 40 to 87 years in the Aerobics Center Longitudinal Study Database (Lee & Blair, 2002). During an average of 10 years of follow-up, high- and moderate-fit men had a 12
68% and 63% lower risk of stroke mortality respectively when compared with low-fit men. The inverse association between cardiovascular fitness and stroke mortality remained even after statistical adjustments for age, cigarette smoking, alcohol intake, body mass index, hypertension, diabetes mellitus, and parental history of coronary heart disease. Therefore, improving aerobic capacity is an important approach to manage and prevent many health-related conditions including stroke. 2.4 Aerobic Training in Chronic Stroke Population Several benefits of aerobic exercise have been reported in healthy population (McArdle, 1996). For example, aerobic training results in metabolic adaptations which include increases in mitochondrial size and number, enhanced activity of aerobic enzymes, and greater capillarization of trained muscle (McArdle, 1996). Moreover, aerobic training stimulates functional and dimensional changes in the cardiovascular system which include lower resting and submaximal exercise heart rate, enlarged left ventricular cavity, increased stroke volume and cardiac output, and a greater arteriovenous oxygen difference (McArdle, 1996). These changes enhance the ability to deliver and use oxygen even during vigorous exercise. In chronic stroke, with a few exceptions, studies have shown positive physiological, psychological, and functional outcomes of aerobic programs (summarized in Table 1). Some studies reported no significant improvement in VO2peak, walking distance, and gait speed following aerobic exercise programs (Lee et al., 2008; Saunders et al., 2004). Also, a recent Cochrane review investigated the effects of aerobic training for stroke patients by complying data from 12 randomized controlled trials, and the authors reported no overall improvements in cardiovascular fitness or self-selected walking speed (Saunders et al., 2004). However, many aerobic training studies on chronic population reported significant improvements in functional outcomes. Table 1 summarizes aerobic training studies on the chronic stroke population, and improvements in cardiorespiratory fitness, walking 13
distance and velocity, quality of life, balance, stride length, muscle strength of affected lower limb, and body composition , and flexibility have been observed. Furthermore, aerobic exercise has been shown to increase the ratio of slow to fast twitch muscles in paretic limb (Hafer-Macko, Ryan, Ivey, & Macko, 2008) and improve glucose tolerance and insulin sensitivity (Ivey, Ryan, Hafer-Macko, Goldberg, & Macko, 2007). Improvements in physical function and control during training and testing sessions also has the potential to increase psychological gains following exercise programs (Teixeira- Salmela et al., 1999). 14
Table 1. Summary of literature: effects of aerobic training in chronic stroke Time Duration / Outcome Findings/Author's Study Design Population since Intervention Intensity Measures Conclusions stroke Ada et al., Randomized, N = 27 6months 4weeks; E: Both treadmill and Walking speed (over The 4-week treadmill and 2003 placebo- (19M; 8F) to 3x/week; overground walking 10m), overground walking controlled Mean age 5 years 30min/session with proportion of walking capacity program significantly clinical trial = 66 treadmill walking (distance over 6min), increased walking speed with decreasing by 10% and handicap (stroke- and walking capacity, but 3-month each week; adapted 30-item did not decrease handicap. follow-up C: Low-intensity, version of the These gains were largely home exercise program Sickness Impact maintained 3 months after to lengthen lower limb Profile). the cessation of training. muscles and to train balance and coordination. Chu et al., Single-blind N = 12 > 1 year 8 weeks; E: Water-based VO2peak, maximal Exercise group 2004 randomized (11M; 1F) 3x/week; exercise program workload, muscle significantly improved controlled trial Mean age 60min/session focusing on leg strength, gait speed, cardiovascular fitness, = 61.9 exercise to improve and Berg Balance maximal workload, gait (Exercise); cardiovascular fitness Scale score. speed, and paretic lower- 63.4 and gait speed; extremity muscle strength. (Control) C: Arm and hand exercises while sitting. Dean et Randomized, N = 12 >3months 4 weeks; E: Circuit program Gait speed, walking Task-related circuit al., 2000 controlled (3 people 3x/week; designed to strengthen distance, timed up training improved walking pilot study withdrew; 60min/session muscles in the affected and go, sit to stand, distance, gait speed, with 2-month 9 people leg and practicing and step test. affected leg force follow-up completed locomotion-related production, and the the study) task; number of repetitions of (7M; 6F) C: Similar to exercise the step test. Mean age group, except it was = 66.2 designed to improve (Exercise); the affected upper 62.3 limb. (Control) 15
Time Duration / Outcome Findings/Author's Study Design Population since Intervention Intensity Measures Conclusions stroke Lee et al., Randomized N = 52 >3months 10-12 weeks; E1: aerobic cycling 6-minute walk No significant differences 2008 controlled trial (28M, 20F) 3x/week; plus sham progressive distance, habitual and between groups on Mean age 60min/session resistance training fast gait velocities, walking distance, gait = 63.2 (PRT); and stair climbing velocity. PRT group E2: sham cycling plus power, significantly improved PRT; cardiorespiratory stair climbing power, E3: aerobic cycling fitness, muscle muscle strength, power, plus PRT; strength, power, muscle endurance, cycling C: sham cycling plus endurance, peak power output, and sham PRT. psychosocial self-efficacy; Aerobic attributes. training group improved indicators of cardiorespiratory fitness. Cycling plus PRT produced larger effects than either single modality for mobility and impairment outcomes. Lennon et Single-blinded N = 48 > 1 year 10 weeks; E: Usual care plus Cardiac risk score Preliminary findings al., 2008 Randomized (28M; 20F) 2x/week; cycle ergometry (CRS), VO2, Borg suggest non-acute controlled trial Mean age 30min/session aerobic exercise Rate of Perceived ischemic stroke patients = 60.5 C: Usual care. Exertion (RPE), can improve their (control), Hospital Anxiety and cardiovascular fitness and 59.0 Depression Scale self-reported depression (Exercise) (HADS), Frenchay and reduce their CRS with Activity Index, a cardiac rehabilitation fasting lipid profiles, program. and resting blood pressure. 16
Time Duration / Outcome Findings/Author's Study Design Population since Intervention Intensity Measures Conclusions stroke Luft et Randomized N = 71 >6months 6months; E: Progressive task- Max treadmill Progressive task-repetitive al., 2008 controlled trial (33M; 38F) 3x/week; repetitive treadmill walking velocity, treadmill exercise Mean age 40min/session exercise (T-EX) overground waling improves walking, fitness, = 63.2 C: Stretching. velocity during 6- and recruits cerebellum- (Exercise); minute walk and 10- midbrain circuits. 63.6 meter walk) and (Control) VO2peak. Macko et Randomized N = 61 >6months 6 months; E: progressive VO2peak, VO2 during T-AEX improves both al., 2005 controlled trial (only 45 3x/week; treadmill aerobic submax effort functional mobility and completed 40min/session training (T-AEX); walking (economy of cardiovascular fitness in the study); C: conventional rehab gait), timed walks, patients with chronic E: including stretching Walking Impairment stroke and is more 22M,10F, plus low-intensity Questionnaire (WIQ), effective than R-Control. Mean age walking (R-Control). and Rivermead = 63; Mobility Index C: 21M, (RMI). 8F, Mean age = 64 Page et Randomized N=7 > 1 year 8 weeks; Group 1: 8 weeks of Lower extremity HEP participation showed al., 2008 controlled (5M; 2F) 3x/week; aerobic training using a scale of the Fugl- no changes on any of the single-blinded Mean age 30min/session recumbent cross trainer Meyer and the Berg outcome measures while crossover trial = 61.29 (NuStep) followed by Balance Scale. NuStep participation 8 weeks of home improved Fugl-Meyer and exercise Berg Balance scores. program(HEP); Group 2: same as Group 1 but in opposite order. 17
Time Duration / Outcome Findings/Author's Study Design Population since Intervention Intensity Measures Conclusions stroke Pang et Randomized N = 63 > 1 year 19 weeks; E: Progressive fitness Maximal oxygen The intervention group had al., 2005 controlled trial E: 3x/week; and mobility and consumption, 6- significantly more gains in 19M,13F, 60min/session mobility exercise minute walk test, cardiorespiratory fitness, Mean age program targeting isometric knee mobility, and paretic leg = 65.8; cardiorespiratory extension, Berg muscle strength than C: 18M, fitness, balance, leg Balance Scale, controls. Femoral neck 13F, Mean muscle, Physical Activity BMD of the paretic leg age = 64.7 strength,mobility, and Scale for Individuals was maintained in the hip bone mineral with Physical intervention group, but density (BMD); Disabilities, and significantly declined in C: Seated upper- femoral controls. extremity program. neck BMD. Pohl et Randomized N = 60 (3 > 4weeks 4 weeks; E1: Conventional Gait speed, cadence, STT group scored al., 2002 controlled trial groups ; N 3x/week; physiotherapy plus stride length, significantly higher than = 30min/session limited progressive Functional LTT and CGT groups for 20/group; treadmill training Ambulation Category overground walking speed, Group1: (LTT); scores (FAC). cadence, stride length, and 13M/7F, E2: Conventional FAC. Group2: physiotherapy plus 14M/6F, structured speed- Group3: dependent treadmill 16M/4F) training (STT); Mean age C: Conventional = 61.6 physical therapy gait (Gr1), 57.1 training (CGT). (Gr2), 58.2 (Gr3) 18
Time Duration / Outcome Findings/Author's Study Design Population since Intervention Intensity Measures Conclusions stroke Potempa Randomized N = 42 >6months 10-week; E: aerobic exercise VO2peak, heart rate, Only experimental subjects et al., controlled trial (23M, 19F) 3x/week; training; workload, exercise showed significant 1995 Mean age 30min/session C: passive range-of- time, resting and improvement in maximal = not motion exercise. submaximal blood oxygen consumption, reported pressure, and workload, and exercise sensorimotor time. Improvement in function. sensorimotor function was significantly related to the improvement in aerobic capacity. Rimmer Randomized N = 35 > 6months Two E: Cardiovascular, Peak VO2, maximal The exercise group et al., pretest/posttest (9M, 26F) 12-week 30min; strength 20min; workload, time to showed 2000 lag control Mean age iterations; flexibility, 10 min; exhaustion, 10RM on significant gains in peak group = 53.2 3x/week; C: No intervention. two LifeFitness VO2, strength, 60min/session strength machines, hamstring/low back grip strength, body flexibility, and body weight, total composition. No skinfolds, waist to hip significance found on ratio, hamstring/low waist to hip ratio, shoulder back flexibility, flexibility, and grip shoulder flexibility. strength. Teixeira- A randomized N = 13 > 9months 10 weeks; E: Program consisting Muscle strength and Significant improvements Salmela pretest and (7M, 6F) 3x/week; of a warm-up, aerobic tone, level of physical were found for all the et al., posttest Mean age 60-90 exercises (10-20min of activity, quality of selected outcome measures 1999 control group, = 67.73 min/session TM walking, stepping life, gait speed. (level of physical activity, followed by a or cycling at 70% quality of life, and gait single-group HRpeak), lower speed) for the treatment pretest and extremity muscle group. posttest strengthening, and a design. cool down; C: No intervention. 19
2.5 Aerobic Training in Subacute Stroke Population Several studies have shown that early aerobic exercise following stroke is safe, and stroke-related impairments at the subacute stroke stage might be improved by such exercise (da Cunha et al., 2002; Tang, Sibley, Thomas, Bayley, Richardson, McIlroy, & Brooks, 2009). However, there are still insufficient data to guide clinical practice, and mixed findings in the literature necessitate further studies. In a previous study from our group, we evaluated the feasibility of adding aerobic training to conventional rehabilitation early after stroke (Tang, Sibley, Thomas, Bayley, Richardson, McIlroy, & Brooks, 2009). Twenty-three patients in the subacute phase after stroke underwent 30 minutes of aerobic cycle ergometer training 3 days/week until discharge from a rehab centre. Findings from our previous study showed a trend towards greater improvements in functional outcomes, and we concluded that early aerobic training could be safely implemented to conventional stroke rehabilitation without deleterious effects. Moreover, stroke-related impairments in the subacute stroke population may be reduced effectively by implementing aerobic exercise programs early after stroke. It is during the first few months following stroke that the most spontaneous recovery takes place (Cramer 2008). Recent evidence from animal literature further supports the importance of early exercise by demonstrating heightened responsiveness to rehabilitative experiences early after stroke which declines with time (Biernaskie, Chernenko, & Corbett, 2004). Early after stroke, patients may be more motivated to participate in rehabilitation programs and willing to adopt an exercise program as their life-long habit. A combination of all these factors emphasizes the importance of early exercise. Despite the potential benefits associated with early aerobic exercise, only a handful number of studies have investigated the effects of aerobic exercise programs in the sub-acute stroke population and reported mixed results (see Table 2). The lack of consensus on benefits of aerobic exercise in this population calls for further trials. 20
Table 2. Summary of literature: effects of aerobic training in sub-acute stroke Time Duration / Outcome Findings/Author's Study Design Population since Intervention Intensity Measures Conclusions stroke Duncan et Randomized N = 20 30-90 12 weeks; E: performed Fugl-Meyer Motor Experimental group al, 1998 controlled Mean age = 67.8 days 3 days/week; exercise program, Assessment, the showed significant pilot study (control), 67.3 90 min/session designed to Barthel Index of improvements only in (experimental) improve strength, Activities of Daily Fugl-Meyer Lower balance, Living (ADL), the Extremity score and gait and endurance Lawton Scale of velocity. No significant and to encourage Instrumental ADL, differences were more use of the the Medical observed in other affected Outcomes Study– measures. extremity. 36 Health Status C: Usual care Measurement, 10- provided m walk, 6-Minute Walk, the Berg Balance Scale, and Jebsen Test of Hand Function. Duncan et Randomized N = 92 30 to 12-14 weeks; E: Various strength, balance, There were trends al, 2003 controlled (50M, 42F) 150 days 36 sessions; exercises motor control, toward greater gains in single-blind Mean age = 70 90 min/session targeting mobility, peak strength and motor clinical trial flexibility, aerobic capacity, control in the strength, balance, upper-extremity intervention compared endurance, and function and with the usual care upper-extremity endurance group, but the function were differences were not prescribed. significant. The C: Usual care intervention group provided showed significant improvments in balance, endurance, peak aerobic capacity, and mobility. 21
Time Duration / Outcome Findings/Author's Study Design Population since Intervention Intensity Measures Conclusions stroke Eich et al, Randomized N = 49
Time Duration / Outcome Findings/Author's Study Design Population since Intervention Intensity Measures Conclusions stroke Tang et al, Prospective N = 23
2.6 Aerobic Exercise and Conventional Stroke Rehabilitation Despite the high prevalence of deconditioning among individuals after stroke, conventional stroke rehabilitation has given limited attention to the benefits of aerobic training on stroke recovery. MacKay-Lyons and Makrides have demonstrated that patients with stroke spent an average of 2.8 minutes in their aerobic exercise target heart rate zone during physical therapy over the course of stroke rehabilitation, representing only 4.8% of the time spent in physical therapy (MacKay-Lyons & Makrides, 2002). The lack of aerobic exercise components in conventional stroke rehabilitation may stem from the view that stroke recovery is dependent on the state of the neuromuscular system imposed by upper motor neuron damage (MacKay-Lyons & Howlett, 2005). The static nature of conventional stroke rehabilitation programs might contribute to the low physical endurance of poststroke patients (Hjeltnes, 1982). Also, other reasons for not systematically addressing cardiovascular issues in stroke rehabilitation may include increased risk of falls, worsening of spasticity, and negative cardiac response to the potential overwork necessary to achieve a training effect; however, such concerns have not been supported (Bateman et al., 2001; Macko et al., 2001). 2.7 Research Rationale and Objective Previously, we have demonstrated that it is feasible to add aerobic cycle ergometer training to conventional rehabilitation early after stroke (Tang, Sibley, Thomas, Bayley, Richardson, McIlroy, & Brooks, 2009). We also reported improvements over time with a trend toward greater aerobic benefit on walking and aerobic capacity in the Exercise group, compared to the Control group. Despite the greater improvements shown in the Exercise group, the differences between the groups were not significant. We suggested that the insignificant results may be attributed to the short training duration (2-4 weeks of training during inpatient rehabilitation), and a longer period of training beyond inpatient rehab would likely contribute to greater benefits. Thus, the objective of this study was to examine the effects of an early aerobic exercise program following stroke that extended 24
beyond inpatient into outpatient rehabilitation on aerobic capacity, walking parameters (walking distance, speed, and symmetry), health-related quality of life, and balance. 2.8 Hypothesis The study hypothesis was that an early aerobic exercise program following stroke that extended beyond inpatient into outpatient rehabilitation would significantly improve aerobic capacity, walking parameters (walking distance, speed, and symmetry), health- related quality of life, and balance throughout the inpatient and outpatient training period. 25
Chapter 3 3.0 Methods 3.1 Participants This study was approved by the Research Ethics Boards at the University of Toronto and the Toronto Rehabilitation Institute (TRI) (REB# 03-092). Upon admission to TRI, patients with hemorrhagic or ischemic stroke were screened for study eligibility from the in-patient stroke rehabilitation unit. The following study criteria (see Table 3) were used for the screening process: Table 3. Participant eligibility criteria Inclusion criteria • Chedoke-McMaster Stroke Assessment (CMSA) Leg Score between 3 and 6 • Ability to understand the process and instructions for exercise training • Ability to provide informed consent Exclusion criteria • Resting blood pressure greater than 160/100 despite medication • Other cardiovascular morbidity which would limit exercise tolerance (heart failure, abnormal blood pressure responses or ST-segment depression > 2mm, symptomatic aortic stenosis, complex arrhythmias) • Unstable angina • Orthostatic blood pressure decrease of >20 mmHg with symptoms • Hypertropic cardiomyopathy • Other musculoskeletal impairments which would limit the patient’s ability to cycle • Pain which would preclude participation • Greater than 3 months post stroke 3.2 Measurements Once consented, participants entered the study and underwent assessments at three prescribed measurement points: baseline, midpoint, and final. When the participants followed the prescribed timeline, baseline measures were obtained upon recruitment into the study during inpatient rehabilitation. Midpoint measures were obtained just prior to discharge from inpatient rehabilitation program at TRI. The participants continued to exercise in an outpatient setting, and final measures were taken after about 6 – 8 weeks of 26
training in the outpatient setting. Many participants had 1-2 weeks of a transition period from inpatient to outpatient programs because of waiting list and scheduling issues and during this time, most of the subjects did not exercise. The time lost during the transition period was added to their training program in order to make the number of training weeks to be approximately 12 weeks. For example, if a participant trained for 4 weeks as an inpatient and there was a 2 week transition period, she trained 8 more weeks, staying in the program for 14 weeks to make up for the 2 week transition period. Figure 1 demonstrates study timelines. 4 - 6 wks 1 – 2 wks 6 – 8 wks Admission Discharge Discharge from hospital from study Admission Intervention Discharge Intervention Discharge Assessment Period Assessment Period Assessment In-patient Stroke Out-patient Stroke Transition Rehabilitation, Toronto Rehabilitation, Toronto Period Rehabilitation Institute Rehabilitation Institute Figure 1. Study timeline summary Before baseline measures were performed, participant characteristics were recorded from hospital medical charts which included birth date, gender, past medical history and co- morbid conditions, and their stroke-related information including lesion type, location, and current medication. There were four participants who did not follow this prescribed timeline. Even though two participants (SA05 and SA31) entered the study as inpatients, they both were discharged from TRI without any inpatient training soon after being recruited into the study. Hence, they were treated as if they were recruited as outpatients and their midpoint assessments were taken after approximately 7-8 weeks of training in their outpatient training. Another two participants (SA28 and SA32) started as inpatients, but because they only underwent a few training sessions before being discharged from TRI, their 27
midpoint measures were not taken at discharge from TRI but rather obtained during their outpatient rehabilitation periods. Primary Measurements Graded Maximal Exercise Test (max test) A graded maximal exercise test was administered to measure peak oxygen consumption of participants on a BiodexTM semi-recumbent cycle ergometer. The participants underwent four maximal exercise tests throughout the course of study: two during baseline measures, one during midpoint measures, and one during final measures. Two tests were conducted during baseline measures to eliminate trial-to-trial practice effects (Tang, Sibley, Thomas, McIlroy, & Brooks, 2006), and they were separated by at least one day to provide participants with sufficient time to recover from the first test. In the course of the study, a max test and a training session were also separated by at least one day to allow the participants enough time to rest after the training session. During the test, they were asked to pedal at a target rate of 50 revolutions per minute (RPM), which does not aggravate inappropriate muscle activities (Brown & Kautz, 1998). If they felt 50 RPM was too slow, they were allowed to pedal faster up to 60RPM. The test protocol began with two minutes of pedaling with the least resistance (10W) as a warm-up, followed by a progressive increase in resistance. The increment of resistance was estimated from the first exercise test, so that a total test time would be 8-10 minutes for each participant. The test was terminated according to American College Sports Medicine guidelines (American College of Sports Medicine, 2006), or if participants were unable to maintain pedaling at their target rate. A MOXUSTM Metabolic Cart was used to measure peak oxygen consumption (VO2peak) and respiratory exchange ratio (RER). If RER of less than 0.85 was achieved during a max test, VO2peak obtained during this test was not considered to be accurate and was discarded. VO2peak with a higher RER was used for baseline since two max tests were conducted. Peak VO2, peak RER, peak work rate (WRpeak), and peak heart rate 28
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