Am J Physiol Regul Integr Comp Physiol 292: R1146 –R1157, 2007.
First published November 2, 2006; doi:10.1152/ajpregu.00225.2006.
Blood pressure regulation in neurally intact human vs. acutely
injured paraplegic and tetraplegic patients during passive tilt
Sevda C. Aslan,1 David C. Randall,1,3 Kevin D. Donohue,2 Charles F. Knapp,1
Abhijit R. Patwardhan,1 Susan M. McDowell,4 Robert F. Taylor,5 and Joyce M. Evans1
1
Center for Biomedical Engineering, Wenner-Gren Research Laboratory, University of Kentucky, Lexington;
Electrical and Computer Engineering, University of Kentucky, Lexington; 3Department of Physiology,
University of Kentucky College of Medicine, Lexington; 4Department of Physical Medicine and Rehabilitation,
University of Kentucky, Lexington; and 5Cardinal Hill Rehabilitation Hospital, Lexington, Kentucky
2
Submitted 30 March 2006; accepted in final form 12 October 2006
Aslan SC, Randall DC, Donohue KD, Knapp CF, Patwardhan
AR, McDowell SM, Taylor RF, Evans JM. Blood pressure regulation in neurally intact human vs. acutely injured paraplegic and
tetraplegic patients during passive tilt. Am J Physiol Regul Integr
Comp Physiol 292: R1146 –R1157, 2007. First published November
2, 2006; doi:10.1152/ajpregu.00225.2006.—We investigated autonomic control of cardiovascular function in able-bodied (AB), paraplegic (PARA), and tetraplegic (TETRA) subjects in response to
head-up tilt following spinal cord injury. We evaluated spectral power
of blood pressure (BP), baroreflex sensitivity (BRS), baroreflex effectiveness index (BEI), occurrence of systolic blood pressure (SBP)
ramps, baroreflex sequences, and cross-correlation of SBP with heart
rate (HR) in low (0.04 – 0.15 Hz)- and high (0.15– 0.4 Hz)-frequency
regions. During tilt, AB and PARA effectively regulated BP and HR,
but TETRA did not. The numbers of SBP ramps and percentages of
heartbeats involved in SBP ramps and baroreflex sequences increased
in AB, were unchanged in PARA, and declined in TETRA. BRS was
lowest in PARA and declined with tilt in all groups. BEI was greatest
in AB and declined with tilt in all groups. Low-frequency power of BP
and the peak of the SBP/HR cross-correlation magnitude were greatest in AB, increased during tilt in AB, remained unchanged in PARA,
and declined in TETRA. The peak cross-correlation magnitude in HF
decreased with tilt in all groups. Our data indicate that spinal cord
injury results in decreased stimulation of arterial baroreceptors and
less engagement of feedback control as demonstrated by lower 1)
spectral power of BP, 2) number (and percentages) of SBP ramps and
barosequences, 3) cross-correlation magnitude of SBP/HR, 4) BEI,
and 5) changes in delay between SBP/HR. Diminished vasomotion
and impaired baroreflex regulation may be major contributors to
decreased orthostatic tolerance following injury.
12,000 spinal cord injuries (SCI) occur yearly
in North America. Most SCI involve the cervical spine region,
and patients who sustain cervical spine injuries have lasting,
often devastating, neurological deficits and disabilities. Although the most visible effects of SCI are a loss of motor and
sensory function below the lesion, acute SCI, especially those
occurring in the cervical region, are often associated with
hemodynamic instability. Cardiovascular problems known to
arise from sympathetic nervous system dysfunction include
low resting arterial blood pressure (BP), orthostatic hypotension, autonomic dysreflexia, reflex bradycardia, and cardiac
arrest (2, 5, 8, 28, 49, 50). These cardiovascular conditions
severely limit a patient’s participation in rehabilitation, thus
extending hospital stay, increasing the cost of rehabilitation,
and possibly limiting the effectiveness of other treatment.
Orthostatic hypotension is a common problem, particularly
in the acute phase of recovery (26, 32, 49). Short-term stability
of arterial BP is achieved in large part by appropriate adjustments in sympathetic and parasympathetic outflow from the
central nervous system to cardiovascular effector mechanisms
(6, 35, 40, 42) It is generally assumed that fluctuations in
cardiovascular parameters originate from interactions between
sympathetic and parasympathetic neural branches and other
low-frequency sources (22, 45, 47). Spontaneous oscillations
of heart rate (HR) and BP can be analyzed to extract frequencyrelated information. In particular, two rhythms are generally
observed in short-term heart rate recordings: a respiratory or
high-frequency (HF) rhythm (peak ⬃0.2– 0.3 Hz in humans),
considered a marker of vagal activity, and a low-frequency
(LF) rhythm (peak ⬃0.1 Hz in human), a marker of sympathetic activity or combined vagal and sympathetic influence.
Both LF and HF components of HR are influenced by the
gain of the baroreflex (14, 33, 46). The baroreflex provides
negative (i.e., closed loop) feedback regulation that minimizes
the short-term fluctuations in arterial pressure (29). Although
there has been a long-standing interest in assessing baroreflex
characteristics and the importance of determining baroreflex
sensitivity (BRS) is widely recognized, there is no “gold
standard” among techniques for spontaneous baroreflex assessment (40). One of the most frequently employed approaches is
the sequence technique. Sequences of three or more consecutive heartbeats in which a monotonic increase (or decrease) of
systolic blood pressure (SBP) is followed, usually after a delay
of one beat, by a monotonic lengthening (or shortening) of the
R-R interval, are accepted as baroreflex sequences (7). Recently, the baroreflex effectiveness index (ratio between the
total number of baroreflex sequences and the total number of
SBP ramps) was proposed to quantify the number of times that
the baroreflex is effective in driving the sinus node (15).
In addition to assessment of the sensitivity of the baroreflex,
the number of baroreflex sequences that occur provides information concerning overall activity of this reflex (9, 11, 15, 20,
21, 31). To find an absolute value, the occurrence number can
be normalized by time (15, 31), by mean HR (11), by the
Address for reprint requests and other correspondence: J. M. Evans, Center for
Biomedical Engineering, Wenner-Gren Research Laboratory, Univ. of Kentucky,
Lexington, KY 40506-0070 (e-mail: jevans1@pop.uky.edu).
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked “advertisement”
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
orthostatic hypotension; baroreflex sensitivity; baroreflex effectiveness index; cross correlation; feedback
APPROXIMATELY
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BLOOD PRESSURE REGULATION FOLLOWING SPINAL CORD INJURY
number of validated sequences (20), or by the number of
heartbeats (9, 20). The number of baroreflex sequences depends on the number of analyzed heartbeats, and the number of
heartbeats varies among subjects and within a subject according to activity. In addition, each baroreflex sequence can have
various numbers of involved heartbeats, usually ranging from
three to six. Therefore, normalization of the heartbeats involved in baroreflex sequences by the total number of heartbeats in a data segment yields more realistic information on the
occurrence of baroreflex sequences.
Assessing vagal and sympathetic contributions to baroreflex
actions includes decomposition of BP and HR variabilities into
LF and HF periodic components (4, 13, 44). In addition to the
information provided by LF and HF components of BP and
HR, the cross correlation between BP and HR, when considered in the same LF and HF regions, provides both magnitude
and time lag (between the BP and HR variability) information
to quantitatively characterize vagal and sympathetic influences
on autonomic regulation (4).
This study investigates short-term cardiac baroreflex regulation in able-bodied, paraplegic, and tetraplegic subjects
within the first 2 mo following injury. The provocative stimulus was head-up tilt. We compared results from 1) mean
values, 2) spectral power (LF and HF regions), 3) baroreflex
sequence analysis, and 4) the cross correlation between SBP
and HR for their potential to assess cardiovascular deficits
resulting from SCI.
METHODS
Subjects
Eleven healthy, drug-free, able-bodied volunteers (age: 25 ⫾ 4 yr,
means ⫾ SE; 8 men and 3 women) were recruited as a control group.
Five paraplegics (with lesions between T6 and T11; age: 34 ⫾ 15 yr;
4 men and 1 woman), and five tetraplegics (with lesions between C3
and T5; age: 26 ⫾ 9 yr; 5 men) were recruited from patients admitted
to Cardinal Hill Rehabilitation Hospital (CHRH, Lexington, KY) and
studied in their first 8 wk postinjury (Table 1). The following conditions excluded subjects: any orthopedic, neurological, or dermatological disorder that would contraindicate a head-up tilt, as well as deep
vein thrombosis or a psychological disorder. Most SCI subjects were
in some degree of deconditioning secondary to extended bed rest and
immobility, causing some degree of orthostatic intolerance during the
rehabilitation phase. Demographic information of the spinal cordinjured patients is given in Table 1. Subjects 2 and 7 relocated from
the area before their second studies, and subject 10 did not choose to
participate in a second session.
Testing Schedules
Able-bodied subjects were studied once, and spinal cord-injured
subjects were studied twice within 8 wk postinjury. For each SCI
patient, experiments were conducted while they were undergoing
rehabilitation at CHRH. Studies of able-bodied subjects were performed at the General Clinical Research Center (GCRC) at the
University of Kentucky. The able-bodied subjects were admitted on
the day before the data collection session, to provide dietary and
behavioral conditions similar to those at CHRH.
Tilt Protocol
All participants were familiarized with the study and gave informed
consent to a protocol approved by the University of Kentucky Institutional Review Board and the Cardinal Hill Rehabilitation Hospital.
All subjects were studied at least 1 h postprandial and refrained from
AJP-Regul Integr Comp Physiol • VOL
Table 1. Demographic characteristics of spinal
cord-injured patients
Postinjury Time
Subject
No.
Age,
yr
Sex
1
2
3
4
5
31
20
60
23
38
M
M
M
F
M
T11 ASIA A
L1–L3 ASIA A
T10 ASIA A
T5–T10 ASIA A
T10 ASIA A
6
7*
8
9
10
19
30
41
24
19
M
M
M
M
M
C3 ASIA B
T5 ASIA A
C3 ASIA A
C4 ASIA B
C5 ASIA B
Level of Injury
First
session
Second
session
1w,
9w,
4w,
2w,
1w,
2d
4d
1d
3d
2d
2w, 5d
1w,
8w,
1w,
3w,
2w,
5d
3d
5d
6d
3d
Paraplegics
7w, 2d
3w, 2d
2w, 5d
Tetraplegics
3w, 5d
3w, 5d
5w, 4d
The American Spinal Injury Association (ASIA) classifications of spinal
cord injury (SCI) were assessed via the sensitivity of 28 dermatomes and 10
mytomes to pin prick and light touch, and were graded by strength from 0 to
5: ASIA A, complete cord transection: no preserved motor or sensory function
in S4 –S5; ASIA B, sensory incomplete: preserved sensory but not motor
function below the level of injury including S4 –S5; ASIA C, motor incomplete: motor function preserved in more than half of key muscles below the
level of injury, with muscle strength grade less than 3, and sensory function
present below the neurological level including sacral segments S4 –S5; ASIA
D, motor incomplete: preserved motor function in more than half of key
muscles below the level of injury, with muscle strength grade of 3 or greater,
and sensory function preserved below the neurological level including segments S4 –S5; ASIA E, normal: motor and sensory function are normal.
Tetraplegia refers to an injury to the cervical section of the spinal cord.
Paraplegia refers to an injury in the thoracic, lumbar, or sacral section of the
spinal cord. *Behavioral characteristics (difficulty using upper extremities) of
this subject led us to characterize him as tetraplegic rather than paraplegic. w,
Weeks; d, days.
alcohol and caffeine 24 h before the study. All subjects consumed a
fat-free breakfast. Spinal cord-injured subjects wore abdominal binders and support hose. Thirty minutes before study, able-bodied subjects emptied their bladder, and SCI subjects had bladder catheterization. An intravenous cannula (Quick Cath, Baxter) was inserted into
an antecubital vein to obtain blood (six 11-ml samples) for fluid
volume and hormonal analyses for use in another project. Noninvasive
instrumentation, described below, was applied while the subject lay
supine on the tilt table. These preparations took ⬃30 min. All subjects
were fixed to the tilt table by straps at the chest and pelvis.
The study lasted ⬃1 h, beginning with a 10-min period of supine
control, followed by four levels of head-up tilt (20°, 40°, 60°, 80°),
each lasting 7–10 min (rate of tilt ⫽ 2°/s during transition). The
recovery period consisted of 1 min at 20° tilt followed by 7 min
supine. During tilt, members of the research and clinical team continuously monitored the alertness of the subject and hemodynamic
variables. If subjects developed presyncopal symptoms (signs of
fainting) during any part of the study, they were brought to supine
position and the recovery phase began.
Measurement Variables
Beat-to-beat continuous BP was acquired from a finger cuff placed
around the left middle or index finger (Portapres model-2; Finapres
Medical Systems, Amsterdam, The Netherlands). Manual arterial BP
measurements were taken at the beginning of supine control and at the
end of the recovery period from an arm cuff blood pressure measurement device. Eight thoracic impedance (Z) leads were placed on the
neck and thorax to obtain analog ECG, dZ/dt, respiration (from dZ/dt),
cardiac output, and stroke volume (EXT-TEBCO; Hemo Sapiens,
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BLOOD PRESSURE REGULATION FOLLOWING SPINAL CORD INJURY
Sedona, AZ). Calf circumference was acquired via a mercury-inrubber strain gauge placed around the largest part of the left calf
(EC-4 plethysmograph; Hokanson, Bellevue, WA). Tilt angle was
acquired from an accelerometer mounted on the tilt table. Data
presented in this study include only those parameters that provide
insight into reflex regulation of BP through autonomic efferent activity. Other results have been presented in abstract form (3, 19, 23).
Data Acquisition
the filtered sequence was then reversed and run back through the filter.
The resultant series has precisely zero phase distortion. Each signal
was divided into 30-s segments (150 data points) for LF and HF
analysis. Data segments overlapped by 50% and were linearly detrended. Finally, cross-correlation coefficients were calculated, where
the SBP segment was used as the reference signal and the HR segment
was delayed with respect to the reference signal to create the time-lag
axis. All coefficient values were normalized by the product of the root
mean square values of HR and SBP.
All data were acquired at 250 Hz and saved as a Labview file to a
Dell Inspiron 4100. Before analyses, data abnormalities were removed
with the Browser C⫹⫹ program written by Dr. David Brown (Biomedical Engineering, University of Kentucky). For the baroreflex
sequence technique, a Matlab (The MathWorks) program was written
to identify the location of the R wave in the ECG and construct a
beat-to-beat R-R interval time series. The maximum value of arterial
BP between the two R-R intervals (in ms) was computed and resulted
in beat-by-beat sampled SBP. For the cross-correlation technique, HR
was computed from ECG, SBP was computed from continuous BP,
and both variables were then down-sampled to 5 Hz, all using
Browser. All analyses were done using Matlab.
Mean values from the two studies on the SCI subjects were used for
statistical analysis. Differences within and between the three groups
(able bodied, paraplegic, and tetraplegic subjects) during supine
control, the four levels of head-up tilt, and recovery were tested for
significance using a two-factor ANOVA. The group factor was used
to indicate differences among the three groups. The tilt factor was
used to indicate tilt effects for all groups. The group ⫻ tilt factor was
used to determine the significance of differences in tilt effects among
groups. A P value ⱕ 0.05 was accepted as indicating statistical
significance. Results are presented as means ⫾ SE.
Data Analysis
RESULTS
Spectral power. Data from the last 10 min of supine control and the
last 5 min at each level of tilt (20°, 40°, 60°, 80°) and recovery were
used to calculate spectral power, based on Welch’s averaged periodogram technique. Power spectral density estimates were made from
500-point windows with 50% overlapping segments using Matlab.
Total spectral power was calculated for LF (0.04 – 0.15 Hz) and HF
(0.15– 0.4 Hz) regions (40, 47).
Baroreflex sequences. A computer program similar to those of
Blaber et al. (9) and Di Rienzo et al. (15) was written to scan the
beat-to-beat time series of SBP and R-R intervals using 1 mmHg
(SBP) and 4 ms (R-R interval) as minimum thresholds. The last 5 min
of data acquired from each tilt position were used for analysis. Three
or more consecutive beats that independently contained increasing
and decreasing pressure (SBP⫹, SBP⫺) and R-R interval (RR⫹,
RR⫺) sequences were identified. Any SBP beats that fell within
Portapres servo adjustments were excluded. The total number of
excluded beats was ⬍1% of the total number of analyzed beats. If an
identified SBP sequence was followed by an identified RR sequence
with delays of zero, one, or two beats, these SBP and RR sequences
were assigned as coupled. Only coupled sequences with regression
coefficients r ⬎ 0.90 were accepted as baroreflex sequences: a
positive baroreflex sequence included coupled SBP⫹ and RR⫹, and
a negative baroreflex sequence included coupled SBP⫺ and RR⫺
sequences. The mean slope of the baroreflex sequence was calculated
and taken as an estimation of the BRS (ms/mmHg). The numbers of
beats involved in SBP ramps and baroreflex sequences were determined at each tilt position. Since the mean R-R interval varied among
subjects and from supine to head-up tilt positions within the same
subject, the number of beats involved in SBP ramps and baroreflex
sequences are reported as the percentage of the overall number of
analyzed heartbeats in the defined segment. The program gave acceptable results when tested on the Eurobavar data set (30). The
baroreflex effectiveness index (BEI) was evaluated as the ratio between the total number of baroreflex sequences and the total number
of SBP ramps (15). Positive BEI, the ratio between positive baroreflex
sequences and SBP⫹, and negative BEI, the ratio between negative
baroreflex sequences and SBP⫺, were also analyzed to determine the
“selective” responsiveness of the baroreflex to rising (SBP⫹) and
falling (SBP⫺) blood pressure (15).
Cross-correlation analysis. The last 5 min of the HR and SBP time
series from each tilt interval were filtered using fourth-order Butterworth band-pass filters to include oscillations in LF (0.04 – 0.15 Hz) or
HF regions (0.15– 0.45 Hz). After filtering in the forward direction,
At their first session, three able-bodied, one paraplegic, and
three tetraplegic subjects demonstrated symptoms of presyncope at the end of 60° head-up tilt and were returned to the
supine position immediately. The paraplegic and one of the
tetraplegic subjects were able to finish the protocol at their
second session. The four remaining paraplegics finished the
protocol at both their first and second sessions. Illustrative data
from one able-bodied (left) and one tetraplegic subject (right,
C4 incomplete) are shown in Fig. 1. Blood pressure (channel 2)
was well regulated in the able-bodied subject during head-up
tilt, including appropriate increases in HR (channel 1) and
peripheral resistance (not shown). The poor control of BP and
HR during head-up tilt shown in Fig. 1 for the presyncopal
tetraplegic patient was characteristic of this group.
AJP-Regul Integr Comp Physiol • VOL
Statistical Analysis
Mean Values
Average (⫾SE) SBP and HR data for able-bodied, paraplegic, and tetraplegic subjects are given in Fig. 2, A and B.
Able-bodied and paraplegic subjects maintained BP throughout the tilt sequence, whereas tetraplegics exhibited a significant reduction in BP under increasing orthostatic stress (Fig.
2A). In addition, paraplegics had higher mean HR than the
other groups, and tetraplegics were significantly less effective
in increasing HR to accompany the tilt-induced decrease in BP
(Fig. 2B).
Mean breathing frequency in resting control occurred at
0.29 ⫾ 0.01 Hz for able-bodied subjects and 0.31 ⫾ 0.02 Hz
for paraplegic subjects and remained fairly stable throughout
the tilt. The mean breathing frequency of tetraplegic subjects
ranged from 0.16 to 0.48 Hz at control with no consistent
response to head-up tilt.
Spectral Power
The LF spectral powers of BP (LFBP) at rest and each level
of head-up tilt are given in Table 2. In the LF region, ablebodied but not paraplegic or tetraplegic subjects increased LF
power in response to tilt, and tetraplegic subjects had lower
values than both able-bodied and paraplegic subjects. In the HF
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BLOOD PRESSURE REGULATION FOLLOWING SPINAL CORD INJURY
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Fig. 1. Time series for one able-bodied (AB)
and one spinal cord-injured (SCI; tetraplegic)
subject undergoing increasing levels of head-up
tilt (HUT). After supine control, each subject
was tilted to 20°, 40°, 60°, and 80° and returned
to the supine position. Each tilt angle was held
for 7–10 min. The SCI subject was returned to
supine position upon the development of symptoms of presyncope. The AB subject used increases in heart rate (HR; bpm, beats/min) to
regulate blood pressure (BP), whereas the SCI
subject was much less successful in regulating
BP and HR. Calf circumferences, an estimation
of blood pooling to the lower extremities, were
not different between subjects, probably because
SCI wore support hose.
region, there was a significant overall effect of tilt to decrease
power, but the interaction among groups and tilt was not
significant (data not shown).
Baroreflex Sequences
Baroreflex sensitivities (slope of the R-R interval-SBP relationship) at rest and during head-up are given in Table 3 for all
groups. The lower slope of BRS in paraplegic compared with
able-bodied subjects was significant only in recovery. The
group ⫻ tilt interaction results apply to the tilt-induced decrease in BRS that was significant in able-bodied and tetraplegic subjects but not significant in paraplegic subjects.
The average (⫾SE) percentage of heartbeats involved in
SBP ramps (A) and in baroreflex sequences (B) are given for all
groups in Fig. 3. The actual numbers of blood pressure ramps
that occurred were also lower in both SCI groups than in the
able-bodied group (data not shown). Each index increased
significantly in able-bodied subjects, remained relatively unchanged in paraplegics, and declined in tetraplegics with increasing tilt angle. Both SCI groups had significantly lower
values than the able-bodied group at each tilt position.
Only group and tilt main effects, but not their interaction,
were significant for the BEI, which was greater in able-bodied
than in tetraplegic subjects and declined with increasing tilt in
all groups (Fig. 4). Positive and negative BEI values were
similar at each tilt level.
Cross Correlation
Cross correlation of BP and HR can be used to evaluate both
direct and inverse relationships between BP and HR (4). Figure
5 shows simultaneous 50-s recordings of SBP (A) and HR (B)
and the cross correlation between the two variables (C) for one
able-bodied subject at 80° head-up tilt. The cross correlation in
Fig. 5C has two main features: the magnitude of the correlation
on the vertical axis and the lead/lag time between SBP and HR
AJP-Regul Integr Comp Physiol • VOL
on the horizontal axis. A correlation magnitude value of ⫹1
indicates perfect direct association between these two signals;
⫺1 indicates a perfect indirect association. Just to the left of
zero in Fig. 5C on the abscissa lies the principal negative
cross-correlation peak. Since SBP was used as a reference
signal and HR was slid backward and forward, negative lags
refer to SBP leading HR. One would expect an inverse relationship between SBP and HR, with SBP leading, if the
baroreflex were figuring importantly in BP regulation. Restated, the negative peak value of ⫺0.86, occurring around
⫺1.5 s, indicates that changes in SBP drive opposite (feedback) changes in HR with an ⬃1.5-s time delay. There is also,
however, a positive peak of ⫹0.75 at ⬃4.5 s (i.e., to the right
of zero lag), indicating that changes in HR resulted in samedirectional (i.e., direct, not inverse) changes in SBP with a
4.5-s time delay.
Indexes of Sympathetic Activity
Figure 6 displays the SBP/HR cross correlation developed in
Fig. 5 with the added feature of tracking the correlation across
time (abscissa in each box). In effect, the correlation in Fig. 5C
has been rotated 90° counterclockwise (positive lags corresponding to SBP lagging HR are shown above zero) with
sequential correlations across time chained together (time progressing left to right for each segment). Data are given as the
group-averaged LF (0.04 – 0.15 Hz) cross correlations for ablebodied, paraplegic, and tetraplegic studies at rest (supine control), in response to tilt, and during recovery from tilt. The
magnitudes of the cross-correlation values are color coded
according to the color bars indicated: positive values are shown
in yellow/red, whereas negative values are shown in blue/
violet. The time in minutes (i.e., progression of the experiment)
is plotted along the horizontal axes for each tilt angle. The
able-bodied group had strong negative and positive interactions
(blue and red bands, respectively) at all tilt levels. Paraplegics
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BLOOD PRESSURE REGULATION FOLLOWING SPINAL CORD INJURY
Figure 7 shows the average cross-correlation magnitude of
the SBP/HR negative peak in the LF region. Although correlation magnitudes were similar for all groups during the initial
supine condition, SCI patients did not exhibit increasing magnitude in response to tilt, as was the case for able-bodied
subjects. In response to tilt, time lags for reaching the LF
maximum negative correlation peak did not change significantly from the control value (1.7 ⫾ 0.1 to 1.8 ⫾ 0.3 s) for
able-bodied subjects. In SCI, time lags were similar to those in
able-bodied subjects at control but were significantly greater at
20° and 40° tilt (2.5 ⫾ 0.4 and 2.1 ⫾ 0.3 s for paraplegics,
3.1 ⫾ 0.8 and 3.2 ⫾ 0.9 s for tetraplegics). In addition, the time
delays in paraplegic subjects were significantly greater than in
able-bodied subjects during recovery. Although the effect was
significant, time lags in tetraplegic subjects were erratic and
difficult to identify at higher tilt levels, probably because the
correlation was obscured by noise and other weakly correlated
processes (note low correlation values).
Indexes of Parasympathetic Activity
Fig. 2. Averaged (⫾SE) systolic blood pressure (SBP; A) and HR (B) for AB
(n ⫽ 11), paraplegic (PARA; n ⫽ 5), and tetraplegic subjects (TETRA; n ⫽ 5)
in response to HUT. TETRA demonstrated decreases in mean BP and less
effective increases in HR in response to increasing orthostatic stress. PARA
demonstrated higher mean HR to accompany the tilt-induced orthostatic stress.
P ⬍ 0.05, SBP: group, tilt, and group ⫻ tilt interaction. P ⬍ 0.05, HR: tilt and
group ⫻ tilt interaction. F, Significantly different from AB (same stress level);
⌬, significantly different from PARA (same stress level); ⽤, significantly
different from control (same group).
maintained strong interactions between HR and SBP during
increasing stress, whereas tetraplegics had weaker interactions
during rest and recovery that essentially disappeared during
higher levels of tilt.
Figure 8 contains group-averaged HF (0.15– 0.45 Hz) cross
correlation between SBP and HR for able-bodied, paraplegic,
and tetraplegic subjects during supine rest, in response to tilt,
and recovery from tilt. Able-bodied subjects had the strongest
blue and red bands, both at rest and during head-up tilt.
Paraplegics had weaker correlations than able-bodied subjects,
but a discernable coordination between the two variables remained throughout the study. Both positive and negative correlations declined with progressive head-up tilt in tetraplegics.
Figure 9 shows the group-averaged magnitude of the HF
negative peak of the cross correlation between SBP and HR in
the HF region. There was an overall tilt effect (decline in
correlation magnitude with increasing tilt angle) and the magnitude of the HF negative peak was greater in able-bodied
subjects than in spinal cord-injured subjects, but there was no
significant interaction. Time lags in this HF region significantly
increased from supine control to 80° head-up tilt in able-bodied
and paraplegic subjects (from 0.2 ⫾ 0.07 to 0.6 ⫾ 0.1 s in
able-bodied subjects; from 0.4 ⫾ 0.09 to 0.8 ⫾ 0.2 s in
paraplegics). The time lags of paraplegic subjects were significantly greater than those of able-bodied subjects at 40°
head-up tilt and recovery. Time lags of tetraplegic subjects
were erratic and subject to much variability; therefore, their
values were not included in the analysis.
DISCUSSION
The present study examined short-term cardiac baroreflex
regulation in able-bodied, paraplegic, and tetraplegic subjects
Table 2. Averaged (⫾SE) spectral power of blood pressure in the LF region for able-bodied,
paraplegic, and tetraplegic subjects in response to head-up tilt
Group
Supine control
20° HUT
40° HUT
60° HUT
80° HUT
Supine recovery
Able bodied
Paraplegic
Tetraplegic
69.7⫾10.2
40.9⫾14.4*
18.3⫾4.5*
59.0⫾6.6
28.9⫾6.4*
13.3⫾4.46*
84.7⫾10.3
37.9⫾11.4*
9.9⫾3.0*
113.0⫾18.2‡
41.1⫾9.54*
14.3⫾5.7*†
129.6⫾28.3‡
43.0⫾9.4*
12.9⫾3.8*†
50.9⫾5.6
47.6⫾14.5
16.9⫾4.27*†
Values are average (⫾SE) spectral power of blood pressure (BP) in the low-frequency region for able-bodied (AB; n ⫽ 11), paraplegic (n ⫽ 5), and tetraplegic
subjects (n ⫽ 5) in response to varying degrees of head-up tilt (HUT). Spectral power of BP in the low frequency (LF) region significantly increased in AB and
decreased in spinal cord-injured subjects (SCI) (group, tilt, and group ⫻ tilt interaction, P ⱕ 0.05). *Significantly different from AB (same stress level).
†Significantly different from paraplegic (same stress level). ‡Significantly different from control (same group).
AJP-Regul Integr Comp Physiol • VOL
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BLOOD PRESSURE REGULATION FOLLOWING SPINAL CORD INJURY
Table 3. Averaged (⫾SE) baroreflex sensitivity index for AB, paraplegic, and tetraplegic subjects in response to HUT
Group
Supine control
20° HUT
40° HUT
60° HUT
80° HUT
Supine Recovery
AB
Paraplegic
Tetraplegic
20.7⫾4.1
9.8⫾3.2
21.9⫾7.1
18.7⫾4.8
7.6⫾2.2
12.8⫾2.8
10.1⫾2.2†
5.2⫾1.5
11.4⫾2.9†
7.2⫾2.7†
3.9⫾0.9
11.1⫾3.4†
5.5⫾2.2†
3.7⫾1.3
5.2⫾2.7†
24.5⫾4.7
7.8⫾2.3*
21.0⫾4.6
Values are average (⫾SE) baroreflex sensitivity index (ms/mmHg) for AB (n ⫽ 11), paraplegic (n ⫽ 5), and tetraplegic subjects (n ⫽ 5) in response to HUT.
Tilt and group ⫻ tilt interaction, P ⱕ 0.05. *Significantly different from AB (same stress level). †Significantly different from control (same group).
during the injured subjects’ acute phase of recovery. There are
three major findings. First, tetraplegic subjects demonstrated a
significant reduction in their ability to regulate BP and HR in
response to tilt. Second, paraplegic and tetraplegic patients
demonstrated significantly reduced input to baroreflexes as
indicated by lower values of LF spectral power of BP, lower
numbers of SBP ramps and percentages of heartbeats involved
in ramps and baroreflex sequences, and a lower BEI than did
able-bodied persons. Third, SCI resulted in a significant reduction in the negative cross-correlation peak and changed the
Fig. 3. Averaged (⫾SE) percentage of heartbeats involved in SBP ramps (A)
and in baroreflex (BR) sequences (B) for AB (n ⫽ 11), PARA (n ⫽ 5), and
TETRA (n ⫽ 5) at rest and in response to HUT. AB significantly increased
both indexes with HUT. Both indexes were significantly lower in PARA and
TETRA than in AB during HUT. P ⬍ 0.05, group, tilt, and group ⫻ tilt
interaction. F, Significantly different from AB (same stress level); ⽤, significantly different from control (same group).
AJP-Regul Integr Comp Physiol • VOL
time delay (between fluctuations in SBP and HR) in response
to increasing levels of head-up tilt. The reduced correlation
occurred in both LF (index of sympathetic activity) and HF
(index of parasympathetic activity) regions, with the major
impact of SCI occurring in the LF region.
Mean Values
HR increased significantly during tilt in able-bodied subjects
and paraplegics and enabled these individuals to maintain BP
during the orthostatic challenge; conversely, the tilt-induced
rise in HR in tetraplegics was not significant and (in combination with small increases in total peripheral resistance) was not
sufficient to maintain stable blood pressure. We hypothesize
that the limited, tilt-induced rise in HR in tetraplegics is a
direct result of disruption of the normal sympathetic innervation of the heart. That is, withdrawal of cardiac parasympathetic nervous activity is the surviving autonomic nervous
mechanism to control HR in these patients; if so, HR can
increase only up to the “intrinsic” rate of the sinoatrial (SA)
node (18). This intrinsic rate, however, is modulated by circulating catecholamines. This latter effect should be substantial
in these SCI subjects, since circulating levels of catecholamines were more than double that in able-bodied subjects both at rest and during tilt (19). We addressed the role of
sympathetic versus parasympathetic denervation in a previous
study in dogs where we demonstrated that intrinsic HR was
significantly reduced after 3 wk of total denervation of the
heart (19). In those animals, selective parasympathectomy of
the SA node accounted for only some of the decline in intrinsic
Fig. 4. Averaged (⫾SE) baroreflex effectiveness index for AB (n ⫽ 11),
PARA (n ⫽ 5), and TETRA (n ⫽ 5) at rest and in response to HUT. The index
was greatest in AB and declined with increasing tilt level in all groups. P ⬍
0.05, group (TETRA ⬍ AB) and tilt effects.
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BLOOD PRESSURE REGULATION FOLLOWING SPINAL CORD INJURY
resulting vaso- and venomotor tone strongly influence results
reported.
Baroreflex
Fig. 5. Fifty seconds of SBP (A) and HR (B) from 1 AB subject at 80° HUT.
The cross correlation between these variables is shown in C, where the
magnitude of the correlation is given on the vertical axis and the lead/lag
between signals is given on the horizontal axis. A negative magnitude denotes
negative feedback (i.e., an inverse relationship between changes in BP and
HR); a positive magnitude denotes a direct relation between signals (i.e., HR
and BP increasing concurrently). Negative lags indicate that SBP led HR, and
positive lags indicate that SBP lagged HR.
rate. We therefore hypothesize that the inability of tetraplegics
to achieve HR comparable to those of able-bodied subjects and
paraplegics was most likely due to injury-related decline in
intrinsic HR, secondary to “denervation” of sympathetic HR
control. As has been previously reported (51), paraplegics had
higher HR, significant at supine control and recovery, than did
able-bodied controls.
Hormonal activity for a subset of these subjects was reported
previously and indicated that, this early after injury, spinal
cord-injured subjects exhibited significantly higher resting and
tilt values of plasma renin activity and catecholamines (particularly epinephrine) than able-bodied subjects (23). In addition,
able-bodied subjects responded to head-up tilt with increasing
values of these substances, whereas levels in spinal cordinjured subjects were tonically elevated. Cardiovascular effects
of chronically elevated vasoactive hormones probably play a
very significant role in setting mean BP and HR. Effects of
these hormones on the other variables measured or calculated
in the present study are not as clear, but we hypothesize that
AJP-Regul Integr Comp Physiol • VOL
Our able-bodied BRS values fell in the range previously
reported for similar subjects in both supine and head-up tilt
positions (16, 20, 25, 30, 36, 52). The BRS did not differ
significantly between able-bodied and tetraplegic subjects (Table 3), an effect previously observed for tetraplegics studied 12
mo post injury (25). The lower BRS in paraplegics that was
significant in recovery can probably be accounted for by the
higher HR of paraplegics. BRS is strongly dependent on the
prevailing HR, an effect that was used to explain the lower
BRS of paraplegic compared with able-bodied subjects of a
previous study (1). In fact, when we plotted the natural logarithm of BRS against HR, we found that able-bodied and
tetraplegic subjects had equivalent BRS values at HR ⬍ 70
beats/min, whereas able-bodied and paraplegic subjects demonstrated similar BRS values at HR ⬎ 75 beats/min (data not
shown). These findings are consistent with the probability that
baroreflex responses to tilt were highly influenced by the
prevailing HR. If so, with BRS strongly being a function of
parasympathetic outflow and vagal control of HR remaining
relatively intact after SCI, our results are in agreement with
prevailing wisdom.
The occurrence of baroreflex sequences has been reported
previously to increase in able-bodied subjects as they were
moved from supine to head-up tilt position (11, 20, 31). Our
able-bodied group demonstrated a tilt-induced increase in the
percentage of heartbeats involved in baroreflex sequences
(from 32 ⫾ 0.02% at rest to 41.3 ⫾ 0.03% at 60° head-up tilt),
within the same range reported by one of these groups (11). In
addition, able-bodied subjects demonstrated increased LFBP
power as well as an increased number and percentage of SBP
ramps during tilt. The situation in paraplegics and particularly
in tetraplegics was quite different. Although control values
were not different from those of able-bodied subjects, neither
paraplegic nor tetraplegic subjects increased the number of BP
ramps or the percentage of heartbeats involved in either baroreflex sequences or SBP ramps during head-up tilt. The smaller
percentages of SBP ramps and baroreflex sequences in response to head-up tilt relative to able-bodied subjects were
significant for both paraplegics and tetraplegics. In addition,
these same paraplegic and tetrapletic subjects exhibited significantly lower LF spectral power of lower body skin perfusion,
an independent measure of vasomotion (23).
We interpret this diminution within the LF range as a direct
result of SCI-induced dysfunction of sympathetic control of
vascular dynamics. Conversely, the similar HF performance of
all three groups probably results from the relatively intact
parasympathetic control of HR in all groups. The combination
of lower values of LFBP, the lower number of SBP ramps, and,
consequently, a lower number of baroreflex sequences, leads us
to conclude that higher levels of SCI resulted in reduced
stimulation to baroreceptors. These results are supported by
spectral power of BP, which was significantly lower in tetraplegics, probably a result of diminished vasomotion following SCI.
Finally, reduced afferent baroreflex stimulation was not
completely responsible for the loss of regulatory capability in
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R1153
Fig. 6. Group-averaged low-frequency (0.04 – 0.15 Hz) cross correlation between SBP and HR for AB (top, n ⫽ 11), PARA (middle, n ⫽ 5), and TETRA
(bottom, n ⫽ 5) at rest (supine control), in response to tilt (20 – 80° HUT), and recovery from tilt (supine recovery). The lead/lag times in seconds are given on
the vertical axes; time in minutes (i.e., during each phase of the study) is plotted along the horizontal axes. The negative lags refer to SBP leading HR; positive
lags refer to SBP lagging HR. The magnitude of the correlation is indicated by the color density: blue represents negative (i.e., inverse cross correlation between
BP and HR changes), whereas red represents positive (direct) correlations. Bar at right shows the magnitude of the correlation. The last 5 min of data from each
tilt position are plotted. The strong blue band around ⫺2 s in AB represents responses characteristic of baroreflex function (e.g., BP increase preceding reflex
HR decrease). This band also is visible in PARA, but with less strength during some orthostatic stress levels. The diminishment in the strength of the feedback
magnitude with increasing orthostatic stress is clearly visible in TETRA. The direct relationship between HR and BP represented by the red band located around
3.5 s remained in AB and PARA but decreased in TETRA under increasing orthostatic stress.
tetraplegics. In able-bodied subjects, the BEI decreased from
65.0 ⫾ 0.03 to 48.7 ⫾ 0.06% between supine and 80° head-up
tilt, whereas BRS decreased from 20.7 to 5.5 ms/mmHg.
Supine control BEI values and parallel decreases in BEI and
BRS in response to orthostatic stress, similar to those of the
present study, have been reported previously (16, 42). Overall
tilt effects were also present for all groups for both BEI and
BRS. In tetraplegics, however, BEI was lower than in ablebodied subjects, an effect that was not significant for BRS.
Therefore, although the BRS index for tetraplegics was similar
to that for able-bodied subjects at each tilt position, their BEI
was significantly lower than that of able-bodied subjects,
indicating a loss of baroreflex effectiveness in driving the SA
node.
Together, our data support the concept that although the
parasympathetically dominated baroreflex lost some capability
to regulate HR in tetraplegics, the principal affect appeared to
be attenuation of (primarily) LF hydrostatic input to the baroreceptors. The mixed sympathetic and parasympathetic innervations of paraplegics and the decreased stimulation to baroreAJP-Regul Integr Comp Physiol • VOL
ceptors probably all contribute to the significant decrease in
BRS in that injury; however, the higher HR of paraplegics also
may contribute.
LF Cross Correlation As an Index of Sympathetic Activity
The tilt-induced increase in the magnitude of the negative
peak of the cross correlation between SBP and HR in the LF
range may index a progressive increase in sympathetic dominance in able-bodied subjects at higher levels of orthostatic
challenge. However, parasympathetic withdrawal is a wellestablished response to increasing orthostatic stress, so we
hypothesize that the amplitude of the negative peak of the cross
correlation actually assesses the balance between the two
divisions of the autonomic nervous system (36). With peripheral vascular and cardiac spinal pathways impaired, paraplegics did not increase their cross-correlation magnitude during
tilt. Tetraplegics steadily lost correlation during tilt, probably
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BLOOD PRESSURE REGULATION FOLLOWING SPINAL CORD INJURY
sympathetic activity (27). The time delay in our able-bodied
group increased significantly from 0.2 ⫾ 0.07 to 0.6 ⫾ 0.1 s
when subjects moved from supine position to 80° head-up tilt.
The time delay in paraplegic subjects also increased significantly from 0.4 ⫾ 0.09 to 0.8 ⫾ 0.2 s in response to tilt,
indicating typical vagal baroreflex control. The group-averaged
time delay in tetraplegic subjects occurred near 0 s at each tilt
level; however, the variance around the mean ranged from 0.2
to 1.3 s. This high variance, coupled with the low coherence,
led us to exclude the tetraplegic group from time delay results
Limitations of the Study
Fig. 7. Group-averaged magnitude of the low-frequency (0.04 – 0.15Hz) negative peak of the cross correlation between SBP and HR at rest and in response
to tilt is shown for AB (n ⫽ 11), PARA (n ⫽ 5), and TETRA (n ⫽ 5). With
HUT, the strength of the correlation significantly increased in AB, persisted at
a weaker level in PARA, and declined in TETRA (P ⬍ 0.05, group, tilt, and
group ⫻ tilt interaction). F, Significantly different from AB (same stress level);
⌬, significantly different from PARA (same stress level); ⽤ significantly
different from control (same group).
plegic patients. All able-bodied subjects demonstrated strong,
constant blue bands at each tilt position, indicating strong,
active feedback control. Although characterized by lower magnitude and longer time delay, the blue band was also consistent
in all paraplegic subjects, except in the 60-yr-old subject who
lost consistant correlation at higher stress levels. Besides demonstrating very low magnitude and erratic time delays, negative correlations in tetraplegic subjects occurred only sporadically, indicating that a demonstrable coupling between changes
in BP and HR occurred in less than one of the 5-min data
segments. Since patients with poor othostatic tolerance had an
increased phase shift between SBP and HR fluctuations, as
well as lower magnitude correlations (20), an increase in time
delay might also contribute to the orthostatic hypotension
problems that occur following SCI.
HF Cross Correlation As an Index of
Parasympathetic Activity
The tilt-induced decrease in the magnitude of the negative
peak of the cross correlation between SBP and HR represents,
we believe, a progressive withdrawal of parasympathetic outflow that was present in all three groups but was more pronounced in SCI subjects. Although both paraplegic and tetraplegic subjects had lower magnitude responses compared
with able-bodied subjects, paraplegics did maintain feedback
control at each tilt level, whereas tetraplegics increasingly lost
control as tilt angle increased. The strong correlation at lower
tilt angles in tetraplegics may be due in part to respiratory
coupling, since our tetraplegic subjects demonstrated greater
breathing fluctuation effects on HR and SBP (3). Previous
studies in able-bodied subjects reported baroreflex latencies of
0.5– 0.6 s (10, 41) and significantly shorter latencies (17) in
response to different types of stimuli. In addition, the time
delay between baroreceptor stimulation and oscillations of R-R
interval have been reported to increase with decreasing paraAJP-Regul Integr Comp Physiol • VOL
One particular challenge we encountered was recruiting SCI
subjects immediately following injury. In addition, the complexity of classifying the injury contributed to large variability
among subjects within the same group, such as complete or
incomplete injury and different levels of injury. Other factors
include variability in SCI tolerance, medications, rehabilitation
progress, and recovery from spinal shock. Able-bodied subjects were studied only one time. We made this decision based
on previous studies in our laboratory, as well as results published by others, indicating that tolerance to a presyncopal
orthostatic stress is reproducible even within a 72- to 120-h
time frame, (24). The mean negative peak magnitudes and time
delays in tetraplegics may not accurately represent the correlation between HR and SBP in some segments, since inconsistent structure of feedback control was common in that
group. Although we did our best to identify the negative peak
magnitude and time delay values to represent each 5-min
correlation, the inconsistencies lead us to conclude that it is
more instructive to view the feedback structure of whole
segments (Figs. 6 and 8). The positive cross correlation between HR and SBP was not addressed in this report. A direct
relation such as this has been attributed in rats to an open-loop
control mechanism (4), which must be considered in a subsequent publication. Impedance measures of cardiac output and
stroke volume, upper and lower body skin perfusions, intra/
extravascular fluid shifts, and vasoactive hormone information
should provide further insight into cardiovascular regulation in
these subjects. These data are not presented in the present
report because of the lengthy nature of their inclusion; however, results of those analyses, reported in abstract form (3, 19,
23), support the present results. Finally, although there is
controversy concerning the relationship between muscle sympathetic nerve activity and LFBP (48), the controversy does not
extend to the use of this measure of Mayer wave activity as an
index of vasomotion (37).
Perspectives
Consistent and reproducible assessment scales are necessary
to define acutely injured patient deficits and to facilitate communication with caregivers regarding the patient’s status (1).
The American Spinal Injury Association scale for neurological
status and the Functional Independence Measure for functional
outcome are the most commonly used scales. Besides the
deficit of motor and sensory functioning following SCI, cardiovascular problems known to arise from sympathetic nervous
system dysfunction also are common in acute SCI, especially
those occurring in the cervical region. Despite these problems,
there is no assessment test available to identify patients’
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R1155
Fig. 8. Group-averaged, high-frequency (0.15– 0.45 Hz) cross correlation between SBP and HR for AB (top, n ⫽ 11), PARA (middle, n ⫽ 5), and TETRA (bottom,
n ⫽ 5) at rest (supine control), in response to tilt (20 – 80 HUT), and recovery from tilt (supine recovery). The lead/lag times in seconds are given on the vertical axes,
and time in minutes (i.e., progression of the experiment) is plotted along the horizontal axes. The negative lags refer to SBP leading HR, and positive lags refer to SBP
lagging HR. The magnitude of the correlation is indicated by the color density: blue represents an inverse relationship, whereas red represents a positive (direct) correlation. Bar
at right shows the magnitude of the correlation; the darker the color, the stronger the correlation. The last five min of data from each tilt position are plotted. The strong
blue band around ⫺1 s in AB represents negative feedback control, which also appears in PARA but with less strength. The diminishment in the strength of the feedback
magnitude with increasing orthostatic stress is clearly visible in TETRA. The red band around 1.5 s remained in AB and PARA but diminished in TETRA during HUT.
cardiovascular deficits following SCI. In this study, we attempted to discriminate able-bodied from spinal cord-injured
subjects, and paraplegics from tetraplegics, by using cardiovascular variables measured at rest and in response to tilt. In
that regard, the magnitude of the cross correlation between HR
and SBP in the LF region, LFBP, percentage of heartbeats
involved in BP ramps, and baroreflex sequences all appear to
be viable diagnostic indicators of the level of autonomic injury
and subsequent recovery.
In summary, able-bodied subjects responded to head-up tilt
with increased LFBP (Table 2), increased number of ramps and
percentage of heartbeats involved in SBP ramps and baroreflex
sequences (Fig. 3), and increased cross correlation between HR
and SBP in the LF region (Fig. 7). That these variables were
diminished in paraplegics and absent in tetraplegics supports
the concept that each is dependent on intact, peripheral sympathetic pathways to the lower body. Together, our data provide evidence that tilt-induced, sympathetically mediated reflex vasomotion and modulation of HR are major components
of BP regulation of orthostatic stress. In the HF region, declines in BEI (Fig. 4) and the HF cross correlation of BP and
AJP-Regul Integr Comp Physiol • VOL
Fig. 9. Group-averaged magnitude of the high-frequency (HF; 0.15– 0.45 Hz)
negative peak of the cross correlation between SBP and HR at rest and in response
to tilt is shown for AB (n ⬎ 11), PARA (n ⫽ 5), and TETRA (n ⫽ 5). Overall tilt
and group effects were observed with AB ⬎ SCI and magnitude decreasing
with increasing tilt (P ⬍ 0.05, group and tilt). F, Significantly different from
AB (same stress level); ⽤ significantly different from control (same group).
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BLOOD PRESSURE REGULATION FOLLOWING SPINAL CORD INJURY
HR (Fig. 9) characterized the response to head-up tilt in all
groups. This decline probably reflects overall withdrawal of
parasympathetic activity in response to tilt. However, lower
values of BEI (Fig. 4) and magnitude of the HF SBP/HR cross
correlation (Fig. 9) in tetraplegics compared with able-bodied
subjects indicate a deficit in parasympathetic regulation of HR
regulation resulting from spinal cord injury in the cervical
region of the spine.
ACKNOWLEDGMENTS
Dr. Helena Truszczynska from the University of Kentucky assisted with the
repeated-measures ANOVA statistical design and analysis. Dr. David Brown,
UK Center for Biomedical Engineering, kindly provided his BROWSER
program for cleaning and aligning data and constructing beat-by-beat HR,
SBP, DBP, and MBP traces for subsequent analysis in Matlab. The team at
Wenner-Gren Research Laboratory, Chaz Hogencamp, Adam Vogt, Will
DeVries, and Evan Baxter, were invaluable in the conduct of studies. Eric
Hartman and customKYnetics developed and assembled the data acquisition
system. Andrea Hartman, RN, coordinated studies with the staff of both
Cardinal Hill Rehabilitation Hospital and the UK General Research Center.
GRANTS
This work was supported by the Kentucky Spinal Cord and Head Injury
Research Trust, UK General Clinical Research Center Grant MM01R022602,
and Cardinal Hill Rehabilitation Hospital.
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