Early Aerobic Exercise Intervention After Stroke: Improving Aerobic and Walking Capacity

 
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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