JOURNAL OF NEUROTRAUMA 25:1467–1475 (December 2008)ª Mary Ann Liebert, Inc.
DOI: 10.1089=neu.2008.0572

Improvements in Orthostatic Instability with Stand Locomotor
Training in Individuals with Spinal Cord Injury
Susan J. Harkema,1,2,3 Christie K. Ferreira,1,2,3 Rubia J. van den Brand,3 and Andrei V. Krassioukov4

Abstract

Prospective assessment of cardiovascular control in individuals with spinal cord injury (SCI) in response toactive stand training. Cardiovascular parameters were measured at rest and in response to orthostatic challenge before and after training in individuals with clinically complete SCI. The goal of this study was toevaluate the effect of active stand training on arterial blood pressure and heart rate and changes in response
to orthostatic stress in individuals with SCI. Measurements were obtained in individuals with SCI (n ¼ 8) prior toand after 40 and 80 sessions of the standing component of a locomotor training intervention (stand LT). During
standing, all participants wore a harness and were suspended by an overhead, pneumatic body weight support(BWS) system over a treadmill. Trainers provided manual facilitation as necessary at the trunk and legs. All
individuals were able to bear more weight on their legs after the stand LT training. Resting arterial bloodpressure significantly increased in individuals with cervical SCI after 80 training sessions. At the end of the
training period, resting systolic blood pressure (BP) in individuals with cervical SCI in a seated position,
increased by 24% (from 84  5 to 104  7 mmHg). Furthermore, orthostatic hypotension present in response to
standing prior to training (decrease in systolic BP of 24  14 mmHg) was not evident (decrease in systolic BP of
0  11 mmHg) after 80 sessions of stand LT. Hemodynamic parameters of individuals with thoracic SCI wererelatively stable prior to training and not significantly different after 80 sessions of stand LT. Improvements in
resting arterial blood pressure and responses to orthostatic stress in individuals with clinically complete cervical
SCI occurred following intensive stand LT training. These results may be attributed to repetitive neuromuscular
activation of the legs from loading and=or conditioning of cardiovascular responses from repetitively assuming
an upright posture.
Key words: cardiovascular control; orthostatic stress; spinal cord injury; stand training

Introduction

C

ardiovascular control is severely disrupted after
cervical and high thoracic spinal cord injury (SCI). Individuals with SCI can experience low resting arterial bloodpressure (BP) or episodes of severe hypertension from autonomic dysreflexia throughout their lifetime (Krassioukov
et al., 2006a; Mathias et al., 2002; Sheel et al., 2005; Teasell
et al., 2000). These individuals can also experience episodesof orthostatic hypotension, characterized by significant decreases in systolic arterial BP in response to postural changes(Krassioukov et al., 2006a; Mathias, 1995). Symptoms of orthostatic hypotension commonly include fatigue or weakness,light-headedness, dizziness, blurred vision, dyspnea, andrestlessness associated with cerebral hypoperfusion. This
cardiovascular dysfunction can cause discomfort, and interfere with rehabilitation efforts and the ability to perform activities of daily living (Illman et al., 2000).
The effects of exercise on cardiovascular function are wellknown; however, individuals with clinically complete SCI are
limited in the ability to activate the neuromuscular systembelow the level of lesion thus potentially reducing the cardiovascular benefits of exercise. Furthermore, cardiovascularresponses that were deconditioned from lack of orthostaticchallenges (assumption of a standing position) may also
contribute to cardiovascular impairments. Pharmacological1

Kentucky Spinal Cord Injury Research Center, Department of Neurological Surgery, University of Louisville, Louisville, Kentucky.
Frazier Rehab Institute, Louisville, Kentucky.
3
Department of Neurology and Brain Research Institute, University of California, Los Angeles, California.
4International Collaboration on Repair Discoveries (ICORD), Division of Physical Medicine and Rehabilitation, and School of
Rehabilitation, Department of Medicine University of British Columbia, and Spinal Cord Injury Program, G.F. Strong Rehabilitation Centre,
Vancouver, British Columbia, Canada.
2

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HARKEMA ET AL.
Table 1. Subject Characteristics

Subject
ID

Sex

Age
(years)Injury
level

AIS

Years
post-injury

Stand LT

A19
A20
A21
A26
A24
A23
A22
A28

M
M
M
M
M
F
M
M

55
24
27
48
41
26
28
21

C5
C5
C5
C6
T4
T4
T6
T6

A
A
A
A
A
A
A
A

14.7
0.7
4.9
29.5
2.1
7.4
0.8
0.8

Unilateral
Bilateral
Bilateral
Unilateral
Bilateral
Bilateral
Unilateral
UnilateralID, identification; C, cervical; T, thoracic; AIS, ASIA Impairment
Scale; Stand LT, stand locomotor training.

and other interventions including, abdominal binders, pressure stockings and functional electrical stimulation have beenused to combat hypotension and low tolerance to orthostatic
stress with limited success (Barber et al., 2000; Faghri et al.,2001, 2002; Mukand et al., 2001; Raymond et al., 1999).
Locomotor training (LT) is a rehabilitation strategy thatallows individuals with SCI to repetitively practice standing
and stepping using body weight support on a treadmill(BWST) with manual facilitation from therapists (Behrman
et al., 2007). Animal and human studies have shown thatspinal interneuronal networks specific to standing and stepping are highly dependent on continuous afferent feedback
and can activate the neuromuscular system below the level oflesion (Barbeau et al., 1998, 2001, 2003; Barbeau, 2003; Behrman et al., 2000; Beres-Jones et al., 2004; Dietz et al., 2004;
Dobkin et al., 2006; Edgerton et al., 2001; Harkema, 2008;
Harkema et al., 1997; Maegele et al., 2002; Pratt et al., 1994;
Rossignol et al., 1996). Previous studies have demonstrated
that cats with a complete thoracic spinal transection were able
to independently stand with activation of hind-limb extensors
and flexors after repetitive task specific stand training (deLeon et al., 1998; Pratt et al., 1994). In the present study, weevaluated the changes in cardiovascular function resulting
from intensive repetitive stand LT training in individuals witha clinically complete SCI.
Methods
Research participants
Eight individuals with SCI volunteered for this study (Table 1). The University of California, Los Angeles Institutional

Review Board approved all experiments and each participant
signed an informed consent before participating in the study.
A clinician assessed the level and extent of injury according to
the International Standards for Neurological Classification of
SCI and the American Spinal Injury Association impairment
scale (AIS) (Marino et al., 2003; Maynard, Jr., et al., 1997).
Somatosensory evoked potential (SSEP) responses were recorded at the cortex during unilateral posterior tibial nerve
electrical stimulation at the ankle. All individuals were classified with a clinically complete SCI, AIS grade A (no motor or
sensory function below the lesion including the sacral segments S4–S5) and an absent SSEP. Participants had a stable
medical condition and did not have a cardiopulmonary disease unrelated to their SCI. Individuals were not taking any
antispasticity or vasoactive medication during the course ofthis study.
Experimental design
Hemodynamic parameters (BP and heart rate [HR]) wererecorded before (0 sessions), during (40 sessions), and after(80 sessions) stand LT. Measurements were obtained in threedifferent positions: sitting, sitting with a harness and standing
with a harness using body weight support (BWS). SCI individuals were fitted with a harness according to a previously
established protocol that reported the effects of the harness
application on the hemodynamic parameters (Krassioukov
et al., 2006b).
Stand LT intervention
During the stand LT training session (60 min, five times
weekly), SCI individuals wore a harness and were suspended
by an overhead, pneumatic BWS system on a treadmill(BWST) (Innoventer, St. Louis, MO). The BWST was used toprovide the maximum load possible while avoiding knee andtrunk flexion. BWS was monitored and recorded from a loadcell placed in series with the cable attached to the harness.
BWS was continuously reduced over the course of the training
as the individual increased the ability to bear weight withminimal or no assistance at the trunk, pelvis and legs. Four
SCI individuals completed the bilateral stand LT (A20, A21,
A23, and A24) and four individuals completed the unilateralstand LT (A19, A22, A26, and A28; Table 2).
A trainer positioned behind the subject assisted with pelvis
and trunk stabilization by applying anterior forces at the pelvis
and=or posterior forces at the shoulders while ensuring that theTable 2. Changes in Systolic (SBP), Diastolic (DBP), and Mean (MBP) Blood Pressures in Individuals
with Cervical and Thoracic SCI in the Seated Position with a Harness (S-H) and Then Standing Position
with a Harness (ST-H) Before and During Stand LT (Assessments at 40 and 80 Sessions)
Prior to the training

Cervical SCI
Thoracic SCI

S-H
ST-H
S-H
ST-H

Session 40

Session 80

SBP

DBP

MBP

SBP

DBP

MBP

SBP

DBP

MBP

105  1282  7*111  12112  966  657  9*76  882  379  865  887  992  5104  12100  8*#117  16117  1170  10*64  10*82  681  881  1176  993  993  9108  8108  12#113  11114  575  474  9#79  479  1286  485  1090  490  9*p < 0.05, comparison of cervical versus thoracic SBP, DBP, and MBP at each session interval (0, 40, and 80 sessions).
#
p < 0.05, within group (cervical or thoracic) comparisons of session interval (40 and 80 sessions) versus baseline (0 sessions).
SCI, spinal cord injury; LT, locomotor training.

BLOOD PRESSURE AND STAND TRAINING IN SPINAL CORD INJURY
trunk and pelvis were not flexed or hyper-extended. Trainers
assisted in maintaining dynamic knee extension by applying
pressure at the tibial tuberosity and stimulation of the patellar
and Achilles tendons to facilitate extensor activity of weightbearing legs. Trainers promoted slight knee flexion in the extended limbs in order to avoid locking of the hips and knees aswell as to stimulate neuromuscular activity. To further promote extensor muscle activation, the BWS was rapidly increased and decreased periodically during the training session.
During bilateral standing, load was distributed between
both limbs, while during unilateral standing the ipsilaterallimb assumed full loading in an extended position and thecontralateral limb was maintained in a flexed position, similar
to mid-swing.
During unilateral standing, flexor muscle activation was
facilitated when needed by the unloaded leg stimulating thehamstrings and tibialis anterior tendons. All trainers provided
facilitation only when needed to promote extensor muscle
activity in both legs (bilateral group) or extensor activity in
one leg and flexor activity in the other leg (unilateral group).
Individuals actively participated in the stand LT session by
maintaining an upright trunk, shifting their body to transfer
load between limbs (bilateral standing) and maintaining knee
extension.
EMG data acquisition and analyses
Following standard skin preparation, disposable bipolar
recording electrodes of fixed inter-electrode distance (Multi
BioSensors, El Paso, TX) were applied and secured with sur-

0 training sessions
100
L SOL
0
-100
100
L TA
0
-100
1000
0
L MH
-1000
1000
0
L VL
-1000
100
0
R SOL
-100
100
0
R TA
-100
100
0
R MH
-100
100
R VL
0
-100

1469

gical adhesive tape. Bilateral surface EMG was recorded fromthe soleus (SOL), medial gastrocnemius (MG), tibialis anterior(TA), medial hamstrings (MH), and vastus lateralis (VL) in all
individuals before and after training (Fig. 1). EMG signals
were filtered with a cut-off frequency of 20–1000 Hz andsampled by an on-line analog to digital (A–D) acquisition
system (National Instruments, Austin, TX) at 1000 Hz. The
EMG amplifier system (Konigsberg Instruments, Pasadena,CA) was coupled to a pulse interval modulator that relayed
data to decoding electronics. A customized LabVIEW (National Instruments, Austin, TX) software was used for acquiring and analyzing EMG data.
Hemodynamic data acquisition and analyses
BPs were manually measured by the same examiner using
a standard calibrated sphygmomanometer (Tycos 509 Mobile
Aneroid, Welch Allyn, Inc.). HR was obtained using an oximeter (Nonin Onyx 9500, Nonin Medical Inc.) on the index
finger of the opposite arm from the BP measurements. Individuals did not exercise, walk or propel their wheelchair forat least 5 min before the sitting hemodynamic measurement.
During each event (i.e., sitting, sitting with harness, andstanding with harness), BP and HR were recorded at 1-min
intervals for a total of 5 min. Mean arterial pressure (MAP)
was calculated for each BP measurement using the formula[DBP þ (SBP  DBP)=3]. Orthostatic hypotension was identified as a reduction of at least 20 mmHg in systolic BP or
10 mmHg in diastolic BP within 3 min of standing (Consensus
Committee, 1996).

80 training sessions

FIG. 1. Representative electromyographic (mV) activity from the soleus(SOL), tibialis anterior (TA), medial
hamstrings (MH), and vastus lateralis(VL) during standing in one individual(C5, AIS A) with cervical spinal cord injury (A20) before (0 sessions, 59% bodyweight support [BWS]) and after (80 sessions, 34% BWS) the stand locomotor
training intervention.

0

seconds

10 0

seconds10

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HARKEMA ET AL.

Statistical analysis
A linear mixed effects (LME) model was fit for systolic anddiastolic BP as measured in the sitting position. The fixed
effects terms in the model were number of treatment sessions,patient type (cervical or thoracic), and the interaction of thetwo. The number of treatment sessions was treated as a factor
rather than a regression parameter, to allow for the hypothesis
tests to be conducted among and within the levels of the fixed
effects terms. The intercepts in the model were treated as
random effects. Models with the identical effect specification
were fit for the change in systolic and diastolic pressure andHR under assumption of a standing position. All hypothesis
tests derived from the linear mixed effects model were conducted at a significance level of 0.05. Statistical analysis was
conducted using the R software package (R v. 2.6.2, The
R Foundation for Statistical Computing, Vienna, Austria).
Data is presented as mean  standard deviation.
Results
Demographic data
Eight individuals with a cervical (n ¼ 4) or thoracic level(n ¼ 4) SCI participated in the study (Table 1). The majority of
SCI individuals were male (88%), with an age range of 21–55
years (average: 33.8  12.6 years). All individuals sustained a
traumatic, clinically complete SCI, and the average time postinjury was 7.6  10.1 years.
Effects of stand LT on body weight load
and muscle activation
Leg loading increased with training (% BWS decreased) inthe bilateral stand trained group (36  11% BWS pre-training,
8  6% BWS post-training) and the unilaterally stand trainedgroup (58  15% BWS pre-training, 34  20% BWS posttraining). All individuals increased extensor neuromuscular
activity of the leg muscles during bilateral standing after the

stand LT intervention as shown by exemplary data from a
research participant with a cervical SCI (A20, Fig. 1).
Effect of stand LT on hemodynamic parameters at rest
Cardiovascular parameters before (0 sessions), during (40sessions), and after (80 sessions) the stand LT intervention
were compared within a group (i.e., within the cervical orwithin the thoracic group) and across groups (i.e., cervicalcompared to thoracic individuals) during the seated position
without a harness (Fig. 2). Average systolic and diastolic
BPs were significantly lower in the cervical group whencompared to the thoracic group before training (SBP=
DBP 84  5=52  8 mmHg and 108  8=66  6 mmHg, respectively; p < 0.05) and after 40 training sessions (SBP=DBP
93  16=60  7 mmHg and 114  13=75  5 mmHg, respectively; p < 0.05). However, there were no significant differences after 80 training sessions. There were significant
increases in systolic and diastolic BPs within the cervicalgroup before and after 80 training sessions, however there
were no significant changes from 0 to 40 sessions. At the endof the stand LT intervention, the sitting resting systolic BP
in the cervical group increased by 20% (from pre- of
84  5 mmHg, to post- of 104  7 mmHg). The thoracic group
did not exhibit significant changes in BP during sitting at any
time point comparison (i.e., 0–40, or 40–80 sessions). Seatedresting HR was not significantly different between the cervicaland thoracic groups before (65  5 and 75  17 bpm, respectively) or after training (72  12 and 75  17 bpm, respectively). Furthermore, there were no significant differences in HR
within a group across the different time points.
Effect of training on postural changes
in hemodynamic parameters
The harness application increases the resting BP parameters in the seated position only in individuals with a cervical
SCI with no significant differences in HR (Krassioukov et al.,FIG. 2. Effect of training on
resting systolic and diastolicblood pressure in sitting position without the harness forindividuals with cervical andthoracic spinal cord injury(SCI). Hemodynamic parameters were recorded prior to thetraining (0 sessions) and at the
middle (40 sessions) and endof the active training (80 sessions). *p < 0.05, comparisonof cervical versus thoracic
systolic and diastolic bloodpressures at each session interval (0, 40, and 80 sessions);#
p < 0.05, within group (cervical or thoracic) comparisonsof session interval (40 and 80
sessions) versus baseline(0 sessions).

Blood pressure (mmHg)

140

120

*

*

100

80

#

*

*

#

60

40
0

40

80

Training Sessions
T-SCI SBP

T-SCI DBP

C-SCI SBPC-SCI DBPBLOOD PRESSURE AND STAND TRAINING IN SPINAL CORD INJURY
2006b). The degree of increase in systolic BP in sitting following harness application declined from 26  13% (22 
11 mmHg) before training to 4  6% (5  5 mmHg) after 80
training sessions.
Regardless of the effect of the harness application, individuals with a cervical injury also had a significant decrease insystolic BP (24  14 mmHg) and diastolic BP (9  13 mmHg)
during orthostatic stress before the stand LT intervention (Fig.
3 and Table 2, compare S-H with ST-H). Following the standLT intervention there was significant improvement of cardiovascular responses to standing in individuals with cervical
SCI (Fig. 3 and Table 2). For example, in individuals with acervical SCI, the average decrease of systolic BP was only0  11 mmHg, ranging from 10 to þ15 mmHg after 80
training sessions. However, individuals with a thoracic SCI
demonstrated minimal changes in BP during orthostatic stressbefore (0  6 mmHg) and after (2  10 mmHg) training. There
were no significant differences in HR between the cervical andthoracic group at any time point or within a group after 40 or
80 training sessions.
Case presentation
A 24-year-old, male, AIS A, with a C5 traumatic injury wasenrolled in the study and had pronounced orthostatic hypotension prior to training (Fig. 4). His systolic BP decreased by
28 mmHg after 3 min of standing with the harness using
the BWST. He also exhibited compensatory tachycardia of
20 bpm. When he started the stand LT intervention, he frequently experienced light headedness and dizziness and had
to be returned to a seated or horizontal position. After 80
stand LT sessions, he demonstrated significant improvementin his cardiovascular response to orthostatic stress. Upon assumption of an upright position with the harness in the
BWST, he exhibited a brief initial increase of systolic and diastolic BPs and was able to maintain stable arterial BPs

#

-20%
-30%

*

20%
10%
0%
-10%
-20%
-30%

Systolic BP (mmHg)

0%

Diastolic BP (mmHg)

Systolic BP (mmHg)
Diastolic BP (mmHg)

10%

#

*

Discussion
This study demonstrated that active stand LT can significantly improve hemodynamic parameters in individuals withchronic clinically complete cervical SCI. Specifically, we
found that, following the training intervention, individuals
with a cervical SCI demonstrated an increase in resting arterial BP. Stand LT also eliminated the orthostatic instability
during their transfer from a seated to a standing position in all
individuals with a cervical SCI. Furthermore, by the end of the
training all individuals were able to maintain their BP while
standing with BWS for one hour. Individuals with a midthoracic injury had stable hemodynamic parameters prior totraining with no significant changes following stand LT.
Cardiovascular control is severely disrupted following SCI(Krassioukov et al., 2006b; Mathias et al., 2002; Teasell et al.,2000). Previously, it was demonstrated that low systolic BP iscommon in the acute period and could persist in individuals
with chronic cervical SCI; and it has an inverse linear relationship with the level of SCI (Claydon et al., 2006a; Mathias,
1995; Mathias et al., 2002; Sidorov et al., 2008). The initial basal
resting systolic BP was significantly lower in individuals witha cervical SCI (84  5 mmHg) when compared to individuals
with a thoracic SCI (108  8 mmHg), consistent with previous
studies (Claydon et al., 2006c; Dela et al., 2003; Krassioukov
et al., 2006a,b). Furthermore, individuals with cervical SCI
consistently demonstrated the presence of orthostatic hypotension following assumption of an upright position using the
BWST prior to stand LT. The decrease in systolic BP of
24  14 mmHg from sitting to standing with BWST was consistent with the orthostatic hypotension definition by the

20%
10%
0%
-10%
-20%
-30%
20%
10%
0%
-10%
-20%
-30%
50%

Heart Rate

50%

Heart Rate

throughout the 60 min of stand training session (data shownfor first 20 min, Fig. 4). After training, this individual did notreport any clinical signs of orthostatic intolerance that he experienced before the stand LT intervention.

THORACICCERVICAL

20%

-10%

1471

40%
30%
20%
10%

40%
30%
20%
10%

0%

0%
0

40

Training Sessions

80

0

40

Training Sessions

80

FIG. 3. Changes in systolic anddiastolic blood pressure and heart
rate in individuals with cervicaland thoracic spinal cord injury (SCI)
during assumption of standing
position (sit to stand with harness)at different intervals of training.
Hemodynamic parameters wererecorded prior to the training (0sessions) and at the middle (40 sessions) and end of active training(80 sessions). *p < 0.05, comparisonof cervical versus thoracic systolicand diastolic blood pressures at eachsession interval assessment (0, 40,
and 80 sessions); #p < 0.05, comparison of systolic and diastolic bloodpressures within group (cervical orthoracic) comparisons of session interval (40 and 80 sessions) versus
baseline (0 sessions).

HARKEMA ET AL.

Heart Rate

1472

HR
HR trained

85
65
45
150

Blood pressure (mmHg)

FIG. 4. Changes in systolic and diastolic blood pressure and heart rate in a
24-year-old man with AIS A, C5 injury
during active standing before and after
completion of course of training. Blackbar indicates the period of assumptionof the standing position with harness
and body weight support (BWS).

SBP
DBP
SBP trained
DBP trained

130
110
90
70
50
30
0

5

10

15

20

time (min)American Autonomic Society and the American Academy of
Neurology (Consensus Committee, 1996). Orthostatic hypotension is a common problem in individuals with SCI, particularly in the acute phase (Corbett et al., 1971; Sidorov et al.,2008). Illman and colleagues reported that 73.6% of individuals with a SCI suffer from orthostatic hypotension during
mobilization treatments (Illman et al., 2000). However orthostatic hypotension continues to be prominent in chronic
SCI. In our recent study we documented that 50% of individuals with a chronic cervical SCI (>1 year after injury) still
experience symptomatic orthostatic hypotension (Claydon
et al., 2006a; Krassioukov et al., 2006a).
It is likely that persistent low resting BP, with episodes oforthostatic hypotension that are common in individuals witha cervical SCI, would have a deleterious effect upon theirhealth. Illman and colleagues reported that the presence oforthostatic hypotension is not only a cause of discomfort forindividuals with SCI but is also associated with a delay of
rehabilitation (Illman et al., 2000). Furthermore, Duschek et al.
(2003) demonstrated that even moderate resting hypotension
in able bodied subjects (systolic pressure below 110 mmHg) is
associated with deficits in cognitive performance. Finally, thepresence of orthostatic hypotension is commonly associatedwith fatigue in the able bodied population (Freeman, 2003;
Wessely et al., 1990) and neck pain in individuals with SCI(Cariga et al., 2002). Both of these factors can adversely impact an individual’s quality of life and participation in rehabilitation.
Previously, numerous mechanisms that could contribute to
the unstable cardiovascular control following SCI, including
orthostatic hypotension, were identified. In our recent review,
we discussed possible mechanisms of developing orthostatic
hypotension following SCI and reported that the pathophysiology of this condition is likely to be multifactorial(Claydon et al., 2006b). First, the loss of the descending
sympatho-excitatory control to the spinal autonomic circuits
and reduction in sympathetic drive below the level of SCI
could be identified as a leading cause of low resting BP andorthostatic hypotension following SCI. The venous pooling
may be greater in paralyzed limbs of individuals with SCI
than in able-bodied subjects in whom skeletal muscle pumping activity promotes venous return and maintains BP (Guyton et al., 1964). There is also an effect of cardiovasculardeconditioning from inactivity in individuals with SCI, especially individuals with tetraplegia. Finally, the alterations insalt and water balance could lead to hypovolemia and predispose these individuals to orthostatic hypotension (Claydon
et al., 2006b; Frisbie et al., 1997).
In a study by Dela et al. (2003), investigators reported thatseated resting mean arterial BP in individuals with tetraplegia
was remarkably low and estimated at 57 mmHg in tetraplegics, 90 mmHg in paraplegics, and 96 mmHg in controls.
Following passive leg movements while seated in a bike, arterial BP increased significantly in all groups ( p < 0.05). The
most pronounced effect was observed in individuals withtetraplegia, where BP reached levels comparable to the control
group. However, this effect was only transient as the arterial
BP dramatically declined despite the initiation of FES exercise
in the lower extremities. Although there are obvious differences in their experimental paradigm with our study, there
are some interesting comparisons between the observed hemodynamic responses. Similar to our study, the majority of
individuals from the Dela study sustained a severe motor
complete injury (AIS A and B). The baseline arterial BP of
cervical and thoracic SCI individuals were similar between
the two studies. Furthermore, similar to the tetraplegics in the
Dela study, the individuals with cervical SCI in our study
were unable to maintain the arterial BP following standing
prior to repetitive stand LT (Fig. 3 and Table 2).
Beneficial effect of stand LT
A sedentary lifestyle with limited physical activity resultsin general deconditioning with pronounced deleterious effects on the cardiovascular system (Erikssen et al., 1998).
Furthermore, Erikssen et al. reported that the level of physicalBLOOD PRESSURE AND STAND TRAINING IN SPINAL CORD INJURY
fitness in healthy middle-aged men is a strong predictor ofmortality and that even minor improvements are associatedwith a significantly lowered risk of death (Erikssen et al.,1998). Unfortunately, individuals with SCI, especially thosewith a high cervical injury, must adapt to a sedentary lifestylebecause of paralysis. A sedentary lifestyle affects the alreadycompromised cardiovascular system in SCI individuals, andcould potentially lead to premature death. Numerous studies
demonstrated that cardiovascular disease is now among theleading cause of death in individuals with SCI (DeVivo et al.,
1999; Garshick et al., 2005). Therefore, increased physical activity achieved with stand LT that provides improvements in
cardiovascular function may lead to improved health outcomes. Eng and co-investigators evaluated mailed survey
questionnaires from 142 individuals with SCI regarding theeffect of prolonged standing on their perceived health andwell-being (Eng et al., 2001). Individuals with SCI who engaged in prolonged standing reported positive perceived
health benefits that included circulation, bladder and bowel
functions, pain control, and sleep. However, the most prevalent benefit was the feeling of well-being reported by 87% of
the participants. The individuals in our study verbally reported less fatigue as well as increased well-being; however,
we did not directly assess these parameters in our study.
One study of individuals with thoracic and cervical SCI reported increased femoral artery compliance but did not show
improvements in baseline cardiovascular parameters after 4
months of body weight supported step training on a treadmill(Ditor et al., 2005). Several factors may have contributed to thedifference in our results. In our study, we analyzed the thoracic
and cervical SCI in separate groups (n ¼ 4, thoracic; n ¼ 4 cervical) while the other investigators combined the individuals(n ¼ 6) with different injury levels. We found significant differences in resting baseline systolic and diastolic BPs between
thoracic and cervical SCI individuals prior to training in thisstudy and in previous studies (Claydon et al., 2006a; Krassioukov et al., 2006a), suggesting that combining these two SCI
populations confounds the interpretation. Furthermore, theintensity of weight bearing was dramatically higher in ourstudy with 60 min of weight bearing, five times weekly compared to only 15 min of weight bearing, three times weekly intheir study (Ditor et al., 2005). The stand LT protocol in ourstudy resulted in the ability of the SCI individuals to bear moreweight while there was no improvement during the bodyweight supported step training protocol. This suggests that theintensity of weight bearing may be an important factor in improvement of cardiovascular function after SCI.
Improvement in orthostatic hypertensive responses during
active (with functional electrical stimulation) standing but notpassive standing using a static standing frame has beenshown in individuals with SCI (Faghri et al., 2001; Jacobs et al.,2003). Faghri and co-investigators reported that the cervical
SCI group had significantly lower systolic BPs and mean arterial BPs in response to orthostatic stress (passive standing)than the thoracic SCI group (Faghri et al., 2001). However, thisdifference was not detectable during active standing withfunctional electrical stimulation that activated the neuromuscular system below the level of lesion. Jacobs et al. (2003)
reported lower HRs during passive standing than active
standing, suggesting a higher cardiovascular demand during
active standing. We have found similar results in the cervicaland thoracic group in our study with stand LT that also1473

activates the leg muscles by providing task specific sensory
cues related to the kinematics and kinetics of weight bearingthat activates spinal circuits to increase efferent motor activity. Activating large leg muscles conceivably increases venous
return which is compromised after SCI. Whether spinal autonomic pathways are also activated by stand LT needs to be
determined.
Limitations and future directions
One limitation of this study was the use of manual BP
recordings. However, this is a standard, clinically acceptableand easily available method to assess cardiovascular function.
Future studies should use continuous beat to beat monitoring
to provide more precise evaluation of changes in cardiovascular parameters. The limited number of research participants
is not optimal, however, it is common among human studies
due to availability of SCI individuals at a given rehabilitation
center. However, detailed quantitative information on relatively few individuals can provide insights to understanding
the complexity of the complications of SCI. Another limitationis that we classified the severity of injury by motor and sensory function using the AIS (Marino et al., 2003) rather thanassessment of the integrity of the spinal autonomic pathways(Krassioukov et al., 2007). However, this assessment is notpresently established as a standard neurologic evaluation of
SCI patients but should be considered in future studies. There
are potential challenges to the widespread utilization of standLT when considering the economic investment of training ofclinicians, the BWST equipment required and that two to
three trained individuals are needed to provide the activitybased intervention. However, LT for standing is less expensive than for stepping and the long-term benefits of improved
cardiovascular function may exceed the cost to the health caresystem over the life span of the individual with a SCI. Futurestudies need to address the cost utility measures of stand LT
and other activity-based therapies that require high intensity
interventions.
Conclusion
Standing is considered beneficial for people with SCI who
are confined to a wheelchair, as immobilization can contributeto secondary pathologies such as osteoporosis, leg muscle
contractures, pressure sores, and muscle atrophy (Saitoh et al.,
1996; Tsuzuku et al., 1999). Standing frames are the most viable option for long term use in individuals with clinicallycomplete SCI; however, improvements in cardiovascular
control have not been reported, potentially because of minimal leg muscle activation. In our study, intensive stand LT
that produced neuromuscular activity below the lesion improved cardiovascular function in individuals after cervical
SCI. Activity-based therapies such as LT, that emphasize repetitive weight bearing and activation of the neuromuscularsystem below the level of lesion, may be important for improvements of secondary complications related to clinicallycomplete SCI, even when recovery of walking is not realized.
Acknowledgments
We thank the research participants for their dedication and valuable contribution to this study. We would also
like to acknowledge the expertise and support during the1474
conduction of this study from Amy Budovitch, Janell Jones,
Carie Zuzick, and other personnel from the Human Locomotion Research Center at UCLA. We acknowledge Douglas
J. Lorenz for his expertise with statistical analysis. This work
was supported by the Christopher and Dana Reeve Foundation (HA2-02012B), Roman Reed Spinal Cord Injury Research
Fund of California (RR 04084532), and NIH (49209 and 16333;
PI Dr. Harkema). We acknowledge the support of collaboration between our laboratories by the grant initiative of Christopher and Dana Reeve Foundation (PI Dr. Krassioukov).
Author Disclosure Statement
No competing financial interests exist.
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