J Appl Physiol 109: 996–1001, 2010.
First published July 22, 2010; doi:10.1152/japplphysiol.00593.2009.
Delayed vasoconstrictor response to venous pooling in the calf is associated
with high orthostatic tolerance to LBNP
T. Hachiya,1 M. L. Walsh,1 M. Saito,2 and A. P. Blaber1
1
Aerospace Physiology Laboratory, Department of Biomedical Physiology and Kinesiology, Simon Fraser University,
Burnaby, British Columbia, Canada; and 2Laboratory of Applied Physiology, Toyota Technological Institute, Nagoya, Japan
Submitted 2 June 2009; accepted in final form 16 July 2010
Hachiya T, Walsh ML, Saito M, Blaber AP. Delayed vasoconstrictor
response to venous pooling in the calf is associated with high orthostatic
tolerance to LBNP. J Appl Physiol 109: 996–1001, 2010. First published July
22, 2010; doi:10.1152/japplphysiol.00593.2009.—Central blood volume
loss to venous pooling in the lower extremities and vasoconstrictor
response are commonly viewed as key factors to distinguish between
individuals with high and low tolerance to orthostatic stress. In this
study, we analyzed calf vasoconstriction as a function of venous
pooling during simulated orthostatic stress. We hypothesized that high
orthostatic tolerance (OT) would be associated with greater vasoconstrictor responses to venous pooling compared with low OT. Nineteen
participants underwent continuous stepped lower body negative pressure at ⫺10, ⫺20, ⫺30, ⫺40, ⫺50, and ⫺60 mmHg each for 5 min
or until exhibiting signs of presyncope. Ten participants completed the
lower body negative pressure procedure without presyncope and were
categorized with high OT; the remaining nine were categorized as
having low OT. Near-infrared spectroscopy measurements of vasoconstriction (Hachiya T, Blaber A, Saito M. Acta Physiologica 193:
117–127, 2008) in calf muscles, along with heart rate (HR) responses
for each participant, were evaluated in relation to calf blood volume,
estimated by plethysmography. The slopes of this relationship between vasoconstriction and blood volume were not different between
the high- and low-tolerance groups. However, the onset of vasoconstriction in the high-tolerance group was delayed. Greater HR increments in the low-tolerance group were also observed as a function of
lower limb blood pooling. The delayed vasoconstriction and slower
HR increments in the high-tolerance group to similar venous pooling
in the low group may suggest a greater vascular reserve and possible
delayed reduction in venous return.
lower body negative pressure; near-infrared spectroscopy; straingauge plethysmography; blood pressure; syncope
A PATIENT WITH POSTURAL ORTHOSTATIC tachycardia syndrome or
with heart failure has difficulty transitioning from the supine to
upright position. Even some healthy people exhibit presyncopal symptoms, such as nausea and dizziness during continuous
standing.
It is well known that vasoconstriction is a key factor in the
regulation of blood pressure (BP) during orthostatic stress.
Total peripheral resistance calculated with cardiac output and
mean arterial pressure (MAP) has been shown to be greater
with high orthostatic tolerance compared with low tolerance
(6). Hormonal agents, such as norepinephrine, vasopressin, and
renin-angiotensin II, are involved in vasomotor control during
lower body negative pressure (LBNP) (4, 9) and consistently
greater plasma angiotensin II concentration with high orthostatic tolerance has been reported (4, 9). Furthermore, it has
Address for reprint requests and other correspondence: A. P. Blaber, Dept.
of Biomedical Physiology and Kinesiology, Simon Fraser Univ., 8888 Univ.
Dr., Burnaby, BC, Canada V5A 1S6 (e-mail: ablaber@sfu.ca).
996
been documented that muscle sympathetic nervous activity
(MSNA), which modulates skin and muscle vasomotor tone, is
augmented with increments in negative pressure (27).
Brown and Hainsworth (3) found that increases in forearm
vascular resistance were greater in normal control subjects than
in orthostatic-intolerant patients during combined head-up tilt
(HUT) and LBNP. Although weak vasoconstriction of vascular
smooth muscles in the forearm has often been considered to be
associated with reduced orthostatic intolerance, it has been
documented that the vasoconstrictor rate in the calf is greater
than that in the forearm (28), mainly due to greater myogenic
responses and increased ␣-adrenergic receptor sensitivity (15).
Vascular beds in the lower limbs are considered to play a
critical role in regulating BP during orthostatic stress due to
their large muscle mass and to their constant exposure to
orthostatic blood accumulation (21). An examination of vascular responses in the calf would, therefore, provide more
relevant information on the relationship between vascular resistance and orthostatic tolerance. However, there is some
controversy with respect to the importance of blood pooling
vasoconstriction on orthostatic tolerance (8, 15).
The purpose of this study was to examine vasoconstriction in
the calf as a function of orthostatic stress and tolerance. Unlike
previous studies, in which responses have been characterized
as either a function of LBNP or HUT, we chose to examine
vasoconstriction in the calf as a function of venous accumulation in the calf. We chose this comparison to venous pooling to
normalize the reflex responses to the inducer of a common
physiological stress. We hypothesized that participants with
low orthostatic tolerance would have a reduced vasoconstrictor
response to venous pooling compared with participants with
high tolerance.
To measure vasoconstriction in the calf we used nearinfrared spectroscopy (NIRS). The degree of oxygenated Hb in
muscle can be used to estimate the arterial vascular responses
of muscle tissue during orthostatic stress (10) and can be
considered an indicator of sympathetically mediated muscle
vasoconstriction during graded LBNP. Since high orthostatic
tolerance has been associated with greater vasoconstrictor
response (9), we hypothesized that a larger oxygenated Hb
reduction as a function of venous blood volume (BV) accumulation would be observed in high-tolerant vs. low-tolerant
participants during graded LBNP.
METHODS
Participants. Nineteen healthy male participants volunteered for
this investigation. The room was kept quiet, and its temperature was
maintained between 22 and 24°C during the experiment. Informed,
written consent was obtained from the participants before each experiment. The study conformed to the standard set by the Declaration
8750-7587/10 Copyright © 2010 the American Physiological Society
http://www.jap.org
CALF VASOCONSTRICTION WITH VENOUS POOLING DURING LBNP
of Helsinki, and the experimental protocols were approved by the
Human Subjects Ethics Committee for the Toyota Technological
Institute and by the office of Research and Ethics for Simon Fraser
University.
BV (plethysmography). To evaluate lower limb BV changes, the
calf belly volume was monitored by mercury strain-gauge plethysmography (EC6, Hokanson Bellevue, WA) (29). The strain gauge was
placed at the point of the greatest girth. The change in calf circumference was expressed as a change in voltage values, which reflected
BV alterations. The BV change was expressed as percent change
(ml/100 ml calf volume).
NIRS. NIRS devices were used to monitor oxygenated and deoxygenated Hb changes, yielding total Hb by summing the two Hb
values. The basic principle of NIRS is explained elsewhere (18).
Briefly, the near-infrared light (700 –900 nm) penetrates skin, subcutaneous, and muscle tissues and is scattered. The scattered light is
detected on the surface. Our system (Omegawave, BOM-L1W, Tokyo, Japan) used two laser wavelengths, 780 and 810 nm. Hb and
myoglobin molecules absorb the light at the specified wavelengths.
However, it can be assumed that oxygenated states of myoglobin
should not be affected by LBNP in the current study, because muscle
movements were not observed through the LBNP observation window, and previous research has indicated lack of movement with this
protocol (11). The NIRS device should mainly detect Hb changes in
muscle tissue sites, such as arterioles, capillaries, and venules, since
the high amount of Hb molecules will absorb all of the available light
passing through these blood vessels (20).
To evaluate changes in Hb oxygenated states in a selective deep
portion of the calf muscle vasculature, the NIRS model (BOM-L1W)
with two photodetectors and one emitter was used. Due to technical
difficulties during experimentation, only 15 participants had deep
NIRS measurements. The set of probes was positioned on the skin
surface of the medial soleus area just below the maximum circumference of the left calf. Soleus muscle is a slow-twitch muscle, with a
large degree of vascularization, and is involved in postural control.
The photodetectors were placed parallel to the calf 2.0 and 3.0 cm
from the emitter. The selective deep NIRS evaluations were provided
by subtracting the superficial portion, obtained by the detector 2.0 cm
from the emitter, from the total portion assessed by the detector at 3.0
cm (16). The remaining signal from ⬃2.0 to 3.0 cm in depth enabled
us to monitor Hb changes primarily from the muscle tissue vasculature. In the previous study (10), our laboratory compared oxygenated
Hb changes in calf with MSNA responses and with blood flow
evaluated plethysmography during graded LBNP, finding that both
variables were significantly correlated. It is believed that oxygenated
Hb responses can reflect vasoconstrictor activities accompanying
blood flow reduction during LBNP.
Heart rate and BP. Heart rate (HR) was recorded continuously by
chest electrocardiography. BP was measured in the right arm every
minute by a noninvasive automated electrosphygmomanometry (Nippon Colin BP 203, Tokyo, Japan). Finger photoplethysmography
(Finapres; Ohmeda, Englewood, CO) was used to monitor instantaneous BP so that a sudden reduction in BP indicating presyncope
symptom could be detected.
LBNP. Participants were placed in the supine position with their
lower body enclosed in a wooden negative-pressure chamber at the
level of the iliac crest. The participants straddled a padded seat with
their legs horizontal at heart level and their feet placed against a foot
plate, which did not hinder blood pooling in the legs. The box was
airtight, and a window allowed the experimenter to monitor mercury
strain-gauge and NIRS probes. The participants were rested in the
supine position for ⬃15 min before the LBNP protocol. Then each
participant underwent 35 min of continuous stepped decompression
from baseline (0 mmHg) to ⫺10-, ⫺20-, ⫺30-, ⫺40-, ⫺50-, and
⫺60-mmHg LBNP each for 5 min or until exhibiting signs of
presyncope [decreased BP (Fig. 1), nausea, or light headedness]. After
completion of the LBNP, there was a 5-min recovery at 0 mmHg.
J Appl Physiol • VOL
997
Fig. 1. An example of the original data from one presyncopal participant. AU,
arbitrary unit; LBNP, lower body negative pressure; Oxy, oxygenated; Deoxy,
deoxygenated.
Plethysmography, NIRS, BP, and HR data were averaged from the
last 3 min of each 5-min pressure stage. The NIRS and plethysmography data were displayed as relative changes from the baseline set as
zero. All data were monitored simultaneously and stored on the
personal computer for later analysis. Analog-to-digital conversion
software (Acqknowledge, Biopac systems, Goleta, CA) was used to
acquire the data.
Statistical analysis. Participants’ data were divided into two groups
[low (Low) and high tolerance (High)], based on their ability to
complete an LBNP test up to ⫺60 mmHg. One-way repeated-measures ANOVA for each Hb value in the calf, and for cardiovascular
parameters (HR and BP), including blood pooling in response to
negative pressure for each group, were performed independently.
When the effects were significant, Student-Newman-Keuls post hoc
analysis was applied. The GraphPad InStat statistical package (GraphPad Software, San Diego, CA) was used for the one-way ANOVA
analysis. Two-way repeated-measures ANOVA was carried out to
examine the main effect of the parameters between High and Low
groups and stage of LBNP (SPSS, Chicago, IL).
Inspection of the data revealed the following linear relations:
oxygenated Hb and calf BV, deoxygenated Hb and calf BV, and
oxygenated Hb and deoxygenated Hb. However, the physiological
responses did not always occur in phase with BV accumulation. For
each participant, progressive linear regression analysis was performed. An initial regression was performed with the last three data
points (highest calf BV changes). Data points were then sequentially
added toward baseline with the regression recalculated for an additional point. At each step, the r2 value was compared with the
previous step. If r2 was ⬍0.85, the previous regression was deemed be
represent the response. The slope was recorded, and the x-intercept
was calculated to determine the “threshold” for the response.
The response between HR and BV was observed to be nonlinear
without a threshold delay. Further analysis with a lack of fit test
revealed that the relationship between HR and calf BV was not linear
and that a quadratic provided the best regression. Therefore, a qua-
109 • OCTOBER 2010 •
www.jap.org
998
CALF VASOCONSTRICTION WITH VENOUS POOLING DURING LBNP
dratic regression, for each participant, was performed to examine the
relationship between HR and calf BV. The coefficients of regression
were compared between High and Low groups via t-tests. Additionally, correlation coefficients between total Hb and deoxygenated Hb
with blood pooling were compared with a t-test. Significance was set
at P ⬍ 0.05. Data were expressed as means ⫾ SE.
RESULTS
Ten participants completed up to ⫺60-mmHg LBNP and
were characterized as having high orthostatic tolerance (High:
21.9 ⫾ 0.5 yr, 173.2 ⫾ 2.0 cm, and 62.6 ⫾ 3.1 kg). The
remaining nine participants, who exhibited presyncope and
did not finish the LBNP protocol, were classified as the
low-tolerant group (Low: 23.4 ⫾ 1.5 yr, 174.4 ⫾ 1.0 cm,
and 65.8 ⫾ 2.1 kg).
Two out of nine participants categorized as low tolerance
stopped the LBNP maneuver during ⫺50 mmHg, and the
remainder withdrew during ⫺60 mmHg. While all data in the
High group were displayed throughout ⫺60 mmHg, those in
the Low group were shown up to ⫺40-mmHg LBNP. Since the
15 participants in the selective deep calf oxygenated Hb experiments either completed ⫺60 mmHg or exhibited presyncope symptoms up to ⫺60-mmHg LBNP, the deep calf NIRS
comparisons were only made up to ⫺50-mmHg LBNP between the High (n ⫽ 9) and Low (n ⫽ 6) groups.
Plethysmography. Blood accumulated in the calf proportional to enhanced negative pressure during LBNP (Fig. 2).
There was no group difference in blood pooling in the calf
muscles up to ⫺40-mmHg LBNP (P ⫽ 0.07). Maximal blood
accumulation at ⫺60 mmHg in the High group was greater
than that in the Low group at each tolerant maximal pressure
level (P ⬍ 0.001).
NIRS. Oxygenated Hb decreased as calf volume increased
with LBNP in both the High and Low groups (Fig. 3). There
was no difference between the slopes of the regressions of the
High and Low groups (P ⫽ 0.15), but the x-axis intercept (BV
threshold) in the High group was significantly higher than that
in the Low group (High: 1.04 ⫾ 0.16%; Low ⫺0.25 ⫾ 0.17%,
P ⬍ 0.05) and was significantly greater from zero (P ⬍ 0.05)
(Fig. 3). In contrast, the x-axis intercept in the Low group was
Fig. 2. Percent changes in calf volume. The measurements were performed by
mercury strain-gauge plethysmography. The blood pooling during graded
LBNP is presented up to ⫺40 mmHg in the low-tolerance group and ⫺60
mmHg in the high-tolerance group. Values are means ⫾ SE; n, no. of subjects.
BL, baseline. *P ⬍ 0.05 vs. control; #P ⬍ 0.05 from the previous LBNP level.
J Appl Physiol • VOL
Fig. 3. Top: mean values for oxy-Hb as a function of LBNP for the hightolerance group () and the low-tolerance group (Œ). Values are means ⫾ SE.
*P ⬍ 0.05 vs. control; #P ⬍ 0.05 from previous values. Bottom: regression
analysis between oxy-Hb and calf blood volume (BV) changes. All of the
individual data are displayed (high tolerance: solid or shaded symbols with
solid lines; low tolerance: open symbols with dashed lines). The average
regressions are shown as a thick solid line for the high-tolerance group and a
thick dashed line for the low-tolerance group.
not different from zero (P ⫽ 0.26). Oxygenated Hb and calf BV
changes in the two groups were highly correlated (High: r2 ⫽ 0.98 ⫾
0.01, and Low: r2 ⫽ 0.96 ⫾ 0.01). Similar results were
observed when oxygenated Hb was compared with deoxygenated Hb (Fig. 4). The regressions of oxygenated Hb and
deoxygenated Hb showed that, between the groups, there was
no difference in slopes and that there was a difference in the
x-intercept (P ⬍ 0.05). The x-intercept for the High group was
greater than zero, and the x-intercept for the Low group was
not.
HR. HR at each pressure level, including baseline, did not
differ between both groups (P ⫽ 0.92) (Fig. 5). The magnitude
of the rise in HR in the Low group from ⫺20- to ⫺40-mmHg
109 • OCTOBER 2010 •
www.jap.org
CALF VASOCONSTRICTION WITH VENOUS POOLING DURING LBNP
Fig. 4. Regression analysis between oxy-Hb and deoxy-Hb. All of the individual data are displayed (high tolerance: solid or shaded symbols with solid
lines; low tolerance: open symbols with dashed lines). The average regressions
are shown as a thick solid line for the high-tolerance group and a thick dash
line for the low-tolerance group.
999
Fig. 6. The quadratic equations between HR and blood pooling as physiological responses. The solid lines indicate the high-tolerance group (mean: thick
line; SE: thin line), and the dashed lines are mean (thick line) and SE (thin line)
for the low-tolerance group. bpm, Beats/min. Inset: a sample regression for one
participant from the high-tolerance group (, solid line) and one participant
from the low-tolerance group (Œ, dashed line).
LBNP was greater than that in the High group at the same
period (P ⬍ 0.05). However, similar HR increments in the
High group were found from ⫺40- to ⫺60-mmHg LBNP
compared with the response in the Low groups from ⫺20- to
⫺40-mmHg LBNP (P ⫽ 0.16). Given the nonlinear nature of
the HR changes with LBNP, HR responses at given leg BV
changes were analyzed with a quadratic regression (Fig. 6).
The second-order coefficient of the Low group was significantly greater than that of the High group (P ⬍ 0.05), indicating that the Low group had larger HR responses at given blood
pooling (P ⬍ 0.05) (Fig. 6).
BP. Similar results between groups were obtained in diastolic (P ⫽ 0.25) and mean (P ⫽ 0.702) BP (Fig. 7). In
contrast, systolic BP in the High group decreased from ⫺10mmHg LBNP (P ⬍ 0.05). Systolic BP in the Low group did
not become significantly lower than baseline until ⫺40-mmHg
LBNP (P ⬍ 0.05) (Fig. 7); however, variability was higher in
the Low group.
Fig. 5. Heart rate (HR) responses during graded LBNP up to ⫺40 mmHg in the
low-tolerance group and ⫺60 mmHg in the high-tolerance group. Values are
means ⫾ SE; n, no. of subjects. *P ⬍ 0.05 vs. control; #P ⬍ 0.05 from
previous values.
Fig. 7. Systolic, mean, and diastolic blood pressure responses during graded
LBNP up to ⫺40 mmHg in the low-tolerance group (open symbols) and ⫺60
mmHg in the high-tolerance group (solid symbols). Values are means ⫾ SE;
n, no. of subjects. *P ⬍ 0.05 vs. control; #P ⬍ 0.05 from previous values.
J Appl Physiol • VOL
DISCUSSION
In this study, we have compared leg vasoconstrictor responses to orthostatic venous pooling rather than level of
LBNP. This novel approach to elicit a better understanding of
the differences between low and high orthostatic tolerance has
led to the major finding of vasoconstriction (estimated by
oxygenated Hb in the selective deep portion of the calf) in both
groups, increased at similar rates, but that the onset of vasoconstriction was delayed in the High group. Furthermore,
greater HR increments in the Low group at given blood pooling
(physiological stress) was also observed. One possible reason
109 • OCTOBER 2010 •
www.jap.org
1000
CALF VASOCONSTRICTION WITH VENOUS POOLING DURING LBNP
is that, as reported by Arbeille et al. (2), extra blood is released
from the splanchnic region of tolerant subjects, and, therefore,
vasoconstrictor responses in lower legs can be delayed.
Responses in the calf. Although we hypothesized that calf
oxygenated Hb in the High group would decrease more compared with that in the Low group, our results showed no
significant difference between High and Low groups when the
slopes of the regression analysis between oxygenated Hb and
BV were compared (P ⫽ 0.152, Fig. 3). However, the x-axis
intercept of the regression line in the High group was greater
than that in the Low group (P ⬍ 0.05) and was positive (P ⬍
0.05). Since oxygenated Hb values never increased, these
results indicate a delayed oxygenated Hb reduction in the High
group. It has been postulated that vasoconstriction may not
occur in some participants during moderate LBNP (⫺15
mmHg) due to vasoconstriction reserve (5). Cook and Convertino (5) observed that MSNA bursts in their presyncopal
participant increased 200% from baseline by ⫺15 mmHg,
whereas their non-presyncopal participant did not exhibit any
significant increase. Our results also indicate that participants
with low orthostatic tolerance exhibit vasoconstrictor responses at early stages of an orthostatic stressor.
Blood pooling in the lower body evaluated by mercury
strain-gauge plethysmography between the groups was not
statistically different up to ⫺40-mmHg LBNP, although blood
accumulation in the Low group was slightly slower than that in
the High group (Fig. 2). However, peak accumulation in the
High group was greater than that in the Low group. These
results are in accordance with previous observations by Sather
et al. (22), who demonstrated that the High group exhibited
higher peak midthigh-leg volume increases during LBNP. The
ability of the high-tolerance participants to hold larger BV in
the lower limbs seems counterintuitive, since vasoconstriction
plays a key role to maintain MAP and reduces blood supply to
the lower extremities. Sympathetic discharges to muscle vasculatures, as well as vasoactive hormones, such as reninangiotensin system and vasopressin-induced vasoconstriction.
However, these hormones also act on kidneys to increase
plasma retention. Plasma renin-angiotensin activities were reportedly consistently higher in the high- compared with lowtolerance individuals (4, 9). A greater increase in vasopressin
in participants with high compared with the low orthostatic
tolerance has been reported (4, 9). These plasma vasoreactive
hormones may contribute to retention of plasma volume and
subsequently allow the high-tolerance individuals to withstand
higher blood pooling in the lower limbs during the 25–30 min
of graded LBNP.
Arbeille et al. (2) indicated that, after head-down bed rest,
portal vein cross-sectional area, which was considered to be in
proportion to the splanchnic blood flow (2), decreased in HUT
test finishers, but, nonfinishers did not exhibit any change
during LBNP. It is generally accepted that vasoconstriction in
the legs is an important factor to prevent excess blood pooling
(19). Furthermore, Xiao et al. (30) indicated that tilt-tolerant
subjects showed high calf compliance and resistance during
HUT test before head-down bed rest. Thus we have attempted
to investigate the relationship of these two parameters by
presenting vasoconstrictor responses as a function of blood
pooling to better clarify their interrelationship.
BP and HR responses. The HR response to LBNP was
nonlinear, with the greatest increment occurring in the latter
J Appl Physiol • VOL
stages of LBNP: ⫺20 to ⫺40 mmHg in the Low group and
⫺40 to ⫺60 mmHg in the High group (Fig. 5). When expressed as function of calf volume accumulation, HR rose
more rapidly in the Low compared with the High group (P ⬍
0.05) (Fig. 6). Since there were no group differences in baseline and peak HR, as well as in BV accumulation as a function
of LBNP, this may provide further evidence that low tolerance
is related to less vascular capacity (22) and attenuated baroreflex sensitivity (7) to orthostatic stress than high tolerance.
Given that MAP was maintained up to ⫺40 mmHg in all
participants, it is likely that a greater increase in HR and earlier
vasoconstriction was required to prevent a reduction in mean
BP in the Low compared with the High group. This would
imply an earlier sympathetic activation with BV accumulation
in the Low compared with High group. Thus it seems that
tolerant individuals have room to delay occurrence of vasoconstriction, possibly due to sufficient blood supply from the
splanchnic region, since vasoconstriction in that region has
been observed in HUT (24) and LBNP (14).
NIRS estimates of vasoconstriction and venous volume in the
calf. Since adipose tissue thicknesses may affect NIRS values,
we measured the adipose tissue thickness for each site in a
subgroup of this study (n ⫽ 13) by skinfold calliper. The calf
thickness was 4.2 ⫾ 0.5 mm. Although we did not measure
adipose tissue thickness at the exact site of the NIRS (26)
probes for all of our participants, the selective deep-calf NIRS
measurement with two detectors excluded the majority of
vascular responses in skin and subcutaneous layers (16) to a
depth of up to 2.0 cm in calf NIRS measurements. Thus the
NIRS values in the selective deep-calf portion should not have
been affected substantially by the fat tissue thickness.
Finally, in a previous study (10), our laboratory suggested
that deoxygenated Hb might reflect venous accumulation
within the calf during LBNP. Similar results were observed for
the relationship between oxygenated Hb and deoxygenated Hb
(Fig. 4) as the comparison of oxygenated Hb to strain-gauge
plethysmography BV (Fig. 3). The very close relationship
observed indicates that deoxygenated Hb may be used for
estimating lower limb venous pooling during orthostatic stress.
Summary. The data did not support our hypothesis that
participants with low tolerance to LBNP would have reduced
vasoconstriction compared with participants with high tolerance to LBNP. The slope of oxygenated Hb compared with BV
accumulation in the calf was the same between groups. Instead,
we observed a delay in the onset of oxygenated Hb reductions
to blood pooling in the group with high orthostatic tolerance.
This early blood flow reduction in the Low group was presumably due to a lack of reserved BV, mainly from the splanchnic
region (2, 24), or limited vasoconstrictor capacity (5). By the
same token, the considerable HR increments from ⫺20- to
⫺40-mmHg LBNP found in the Low group were seen later in
the High group from ⫺40- to ⫺50-mmHg LBNP, and greater
HR increments with blood pooling were observed in the Low
compared with the High group. The High group may maintain
stable mean BP and venous return through release of BV to
central circulation from other vascular beds, such as the
splanchnic region.
GRANTS
This work was supported by funds to M. Saito from the Toyota High-Tech
Research Program, and a Grant-in-Aid for Scientific Research from the Japan
109 • OCTOBER 2010 •
www.jap.org
CALF VASOCONSTRICTION WITH VENOUS POOLING DURING LBNP
Society for the Promotion of Science (nos. 13680064 and 15500464). A. P. Blaber
was funded by the Canadian Space Agency (no. 9F007-020213/001/ST).
DISCLOSURES
No conflicts of interest, financial or otherwise, are declared by the author(s).
REFERENCES
1. Abe T, Tanaka F, Yoshikawa K, Fukunaga T. Total and segmental
subcutaneous adipose tissue volume measured by ultrasound. Med Sci
Sports Exerc 28: 908 –912, 1996.
2. Arbeille P, Besnard SS, Kerbeci PP, Mohty PM. Portal vein crosssectional area and flow and orthostatic tolerance: a 90-day bed rest study.
J Appl Physiol 90: 1853–1857, 2005.
3. Brown CM, Hainsworth R. Forearm vascular responses during orthostatic stress in control subjects and patients with posturally related syncope. Clin Auton Res 10: 57–61, 2000.
4. Convertino VA, Sather TM. Vasoactive neuroendocrine responses associated with tolerance to lower body negative pressure in humans. Clin
Physiol 20: 177–184, 2000.
5. Cook WH, Convertino VA. Association between vasovagal hypotension
and low sympathetic neural activity during presyncope. Clin Auton Res 12:
483–486, 2002.
6. El-Bedawi KM, Hainsworth R. Combined head-up tilt and lower body
suction: a test of orthostatic tolerance. Clin Auton Res 4: 41–47, 1994.
7. El-Sayed H, Hainsworth R. Relationship between plasma volume, carotid baroreceptor sensitivity and orthostatic tolerance. Clin Sci (Lond) 88:
463–470, 1995.
8. Essandoh LK, Houston DS, Vanhoutte PM, Shepherd JT. Differential
effects of lower body negative pressure on forearm and calf blood flow. J
Appl Physiol 63: 994 –998, 1986.
9. Greenleaf JH, Petersen TW, Gabrielsen A, Pump B, Bie P, Christensen NJ, Warberg J, Videbaek R, Simonson SR, Norsk P. Low
LBNP tolerance in men is associated with attenuated activation of the
renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol 279:
R822–R829, 2000.
10. Hachiya T, Blaber A, Saito M. Near-infrared spectroscopy provides an
index of blood flow and vasoconstriction in calf skeletal muscle during
lower body negative pressure. Acta Physiol (Oxf) 193: 117–127, 2008.
11. Hachiya T, Blaber A, Saito M. Changes in superficial blood distribution
in thigh muscle during LBNP assessed by NIRS. Aviat Space Environ Med
75: 118 –122, 2004.
12. Hansen J, Sander M, Hald CF, Victor G, Thomas D. Metabolic
modulation of sympathetic vasoconstriction in human skeletal muscle:
role of tissue hypoxia. J Physiol 527: 387–396, 2000.
13. Homma S, Eda H, Ogasawara S, Kagaya A. Near-infrared estimation of
O2 supply and consumption in forearm muscles working at varying
intensity. J Appl Physiol 80: 1279 –1284, 1996.
14. Hughson RL, Shoemaker JK, Arbeille P, O’Leary DO, Pizzollito KS,
Hughes MD. Splanchnic and peripheral vascular resistance during lower
body negative pressure (LBNP) and tilt. J Gravit Physiol 11: 95–96, 2004.
J Appl Physiol • VOL
1001
15. Imadojemu VA, Lott ME, Gleeson K, Hogeman CS, Ray CA,
Sinoway LI. Contribution of perfusion pressure to vascular resistance
during head-up tilt. Am J Physiol Heart Circ Physiol 281: H371–H375,
2001.
16. Kashima S. Spectroscopic measurement of blood volume and its oxygenation in a small volume of tissue using red laser lights and differential
calculation between two point detections. Opt Laser Technol 35: 485–489,
2003.
17. Levine BD, Buckey JC, Fritsch JM, Yancy JRCW, Watenpauch DE,
Snell PG, Lane LD, Eckberg DL. Physical fitness and cardiovascular
regulation: mechanisms of orthostatic intolerance. J Appl Physiol 70:
112–122, 1991.
18. Mancini DM, Bolinger L, Li H, Kendrick K, Chance B, Wilson JR.
Validation of near-infrared spectroscopy in humans. J Appl Physiol 77:
2740 –2747, 1994.
19. Mano T, Iwase S. Sympathetic nerve activity in hypotension and orthostatic intolerance. Acta Physiol Scand 177: 359 –365, 2003.
20. McCully KK, Hamaoka T. Near-infrared spectroscopy: what can it tell
us about oxygen saturation in skeletal muscle? Exerc Sport Sci Rev 28:
123–127, 2000.
21. Rowell LB .Orthostatic intolerance. In: Human Cardiovascular Control.
New York: Oxford University Press, 1993.
22. Sather TM, Goldwater DJ, Montgomery LD, Convertino VA. Cardiovascular dynamics associated with tolerance to lower body negative
pressure. Aviat Space Environ Med 57: 413–419, 1986.
23. Shiga T, Yamamoto K, Tanabe K, Nakase Y, Chance B. Study of an
algorithm based on model experiments and diffusion theory for a portable
tissue oximeter. J Biomed Opt 2: 154 –161, 1997.
24. Stewart JM, Medow MS, Glover JI, Montgomery LD. Persistent
splanchnic hyperemia during upright tilt in postural tachycardia syndrome.
Am J Physiol Heart Circ Physiol 290: H665–H673, 2006.
25. Stewart JM, Weldon A. The relation between lower limb pooling and
blood flow during orthostasis in the postural orthostatic tachycardia
syndrome of adolescents. J Pediatr 138: 512–519, 2001.
26. Van Beekvelt MC, Borghuis MS, Van Engelen BG, Wevers RA,
Colier WN. Adipose tissue thickness affects in vivo quantitative near-IR
spectroscopy in human skeletal muscle. Clin Sci (Lond) 101: 21–28, 2001.
27. Victor RG, Leimbach WN Jr. Effects of lower body negative pressure on
sympathetic discharge to leg muscles in humans. J Appl Physiol 63:
2558 –2562, 1987.
28. Vissing SF, Scherrer U, Victor RG. Relation between sympathetic
outflow and vascular resistance in the calf during perturbations in central
venous pressure. Evidence for cardiopulmonary afferent regulation of calf
vascular resistance in humans. Circ Res 65: 1710 –1717, 1989.
29. Whitney H. The measurements of volume changes in human limbs. J
Physiol 121: 1–27, 1953.
30. Xiao X, Grenon SM, Kim C, Sheynberg N, Hurwitz S, Williams GH,
Cohen RJ. Bed rest effects on human calf hemodynamics and orthostatic
tolerance: a model-based analysis. Aviat Space Environ Med 76: 1037–
1045, 2005.
109 • OCTOBER 2010 •
www.jap.org