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Departments of 1 Sports Medicine, and 2 Molecular Oncology and Angiology, Research Center on Aging and Adaptation, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
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Calponin is an actin binding protein in
vascular smooth muscle that modifies contractile responses. However,
its role in mean arterial pressure (MAP) regulation has not been
clarified. To assess this, MAP and heart rate (HR) were measured in
calponin knockout (KO) mice, and the results were compared with those
in wild-type (WT) mice. The measurements were performed every 100 ms
during a 60-min free-moving state each day for 3 days. Mice in both
groups rested during ~70% of the total measuring period. The mean HR
during rest was significantly lower in KO mice than in WT mice but with
no significant difference in MAP between the groups. The change in HR
response (
HR) to spontaneous change in MAP (MAP) varied in a
wider range in KO mice with an 80% increase in the coefficient of
variation for HR (P < 0.05), whereas MAP in KO mice
was controlled in a narrow range similar to that in WT mice. The
baroreflex sensitivity (HR/MAP), determined from the change in HR
to the spontaneous change in MAP, was twofold higher in KO mice than
that in WT mice (P < 0.01), whereas there were no
significant differences in the baroreflex sensitivity determined by
intravascular administration of phenylephrine and sodium nitroprusside
between the two groups (P > 0.1). The MAP response to
the administrated doses of phenylephrine in KO mice was reduced to
one-half of that in WT mice (P < 0.01) but with no
significant difference in the response to sodium nitroprusside between
the groups. The differences in HR variability and the spontaneous
baroreflex sensitivity between the two groups completely disappeared
after carotid sinus denervation. These results suggest that the higher
variability in HR for KO mice was caused by the increased spontaneous
arterial baroreflex sensitivity, though not detected by the
intra-arterial administration of the drug, and that the higher
variability of HR may be a compensatory adaptation to the blunted
-adrenergic response of peripheral vessels to sympathetic nervous activity.
carotid sinus denervation; heart rate variability
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
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CALPONIN, also called basic calponin or calponin H1, was first isolated from the chicken gizzard as an actin-binding protein, which was reported to be involved in the regulation of smooth muscle contraction (22). Calponin was reported to reduce unloaded isometric forces and shortening velocity (8, 14, 19, 23) by the inhibition of actomyosin ATPase activity in a reconstituted isolated filament system (26). On the other hand, there have been several studies suggesting that calponin increases the contractile response to norepinephrine (NE) (18) or phenylephrine (PE) (9, 16, 20) by facilitating agonist-induced signal transduction.
With the exception of these in vitro studies, however, there have been
few studies investigating the role of calponin in arterial pressure
regulation in the whole body. Because arterial pressure is determined
from the product of cardiac output and total peripheral resistance, the
dysfunction of vascular smooth muscle contraction itself and/or the
impaired -adrenergic response to sympathetic nervous activity in
genetically calponin-deficient mice [knockout (KO) mice] would make
arterial pressure unstable. Alternatively, baroreflex control would
compensate for the impaired arterial pressure regulation by changing
the heart rate (HR) and/or cardiac output in the group.
To examine these hypotheses, we measured mean arterial pressure (MAP)
and HR in the free-moving KO mice and determined the baroreflex
sensitivity from the change in heart rate (HR) in response to the
spontaneous change in MAP (MAP) and compared the results with those
in wild-type (WT) mice. We also determined the baroreflex sensitivity
by intravascular administration of -adrenergic agonist of PE or
sodium nitroprusside (SNP) and compared the results between the groups.
Moreover, we assessed the effects of carotid denervation on MAP to
examine the compensatory effects of baroreflexes, if any, in the KO mice.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
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Animals
The KO mice used in the present study were generated from the same cell line in previous studies (14, 23, 27). Briefly, calponin H1 gene was cloned from a 129SVJ mouse genomic library, and the fragment containing exons 5-7 was replaced with pMC1neopGKgpt. Clones that underwent homologous recombination were injected into C57BL/6J blastocysts. In the present study, we compared MAP regulation between the mice lacking calponin H1 gene (KO mice) and the mice carrying normal calponin H1 gene (WT mice). Absence of calponin H1 expression in the aorta of the KO mice was confirmed by RT-PCR (Fig. 1) and Western blotting with a calponin H1-specific antibody, as reported elsewhere (14, 27). Yoshikawa et al. (27) reported that other isoforms of calponin were not overexpressed in the embryonic cells by RT-PCR in the KO mice from the same cell line as in the present study. Adult male mice aged 10-29 wk (WT, n = 17, 30.3 ± 0.9 g body wt, and KO, n = 16, 31.9 ± 1.3 g body wt) were housed in cages at 25°C with the lights on from 7 AM to 7 PM. Food and water was given ad libitum. The mice were closely monitored to ensure that none experienced undue stress or discomfort.
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The procedures used here were in accordance with the American Physiological Society's "Guiding Principles for Research Involving Animals and Human Beings" and conducted with permission from the Animal Ethics Committee of Shinshu University School of Medicine.
Surgical Procedures
Intact condition. Details were reported elsewhere (15). Briefly, the arterial catheter was fashioned from a 450-mm segment of polyethylene tube (SP31, ID: 0.5 mm, OD: 0.8 mm, Natsume; Tokyo, Japan) welded to a 22-mm polyethylene tube segment (SP8, ID 0.2 mm, OD 0.5 mm, Natsume) with a tip that was tapered to ~0.3 mm in diameter over hot air. At least 4-6 days before the experiment, the mice were anesthetized with pentobarbital sodium (50 mg/kg body wt ip), and the hair over the anterior left lower limb and between the scapulas was shaved. The skin was sterilized with povidon iodine (Meiji; Tokyo, Japan). The surgery was performed on a warming pad kept at 37°C (model 39, DP Scientific; Braintree, MA). The left femoral artery was exposed, and a small incision was made in the arterial wall with microspring scissors. The tip of the catheter was introduced through the incision and advanced by ~20 mm so that the tip was placed 5 mm below the bifurcation of the left renal artery. The catheter was secured to the leg muscle and tunneled subcutaneously and exteriorized between the scapulas. The exteriorized catheter was connected to a cannula swivel (model TCS2-21, Tsumura; Tokyo, Japan), and the mice were placed in a home cage with a free-moving system (Tsumura). A few hours after the preparation, the mice recovered to move the catheterized limb freely. The catheter was flushed everyday with 500 IU heparin in 0.2 ml of saline. The mice were allowed to recover for 4-6 days after catheter implantation before the measurements were taken.
Carotid denervated condition.
At least 3 days after arterial catheter implantation, mice were
anesthetized again as described above. A midline incision was made in
the anterior neck and the area of the carotid bifurcation was exposed.
The internal, external, and common carotid arteries were stripped of
connective tissues, and the region was painted with 10% phenol in
ethanol, as reported previously in rats (12, 24). The
recovery period from the carotid denervation was at least 4 days before
the measurements of HR and MAP. The success of the denervation was
confirmed by the increased fluctuation in MAP and no HR response to the
fluctuation as in Table 1
(4).
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Measurements
MAP was measured through the arterial catheter connected to a pressure transducer (model TP-400T, Nihon Kohden; Tokyo, Japan), with an amplifier (DC Strain Amplifier 6M77, NEC; Tokyo, Japan). HR was counted from the arterial pressure pulse with a tachometer (model AT-601G, Nihon Kohden). The response time of the tachometer at a given change in the pressure pulse rate was 100 ms, which was short enough to detect theHR in the present study. MAP was continuously recorded
with a digital data recorder (Thermal Arraycorder WR 8500, Graphtec;
Yokohama, Japan) at 100-ms intervals through a low-pass filter
(recorder frequency 1.5 Hz) to remove pulsatile arterial pressure
signals. MAP and HR were measured in their home cages during a 60-min
period, randomly chosen between 9 AM and 4 PM, and the measurements on
the same mouse were conducted three times on separate days. Figure
2 shows a typical example of HR and MAP
measured for 60 min in a free-moving WT mouse. The resting period was
distinguished from the moving period according to three criteria:
1) virtually not moving, 2) <10-mmHg increase in
MAP, and 3) <90 beats/min increase in HR. The coefficient
of variations (CVs) of HR and MAP during rest in each mouse were
determined as the values averaged for ~135 min (~45 min × 3 days). The means ± SE for 6 WT and 6 KO mice are presented in
Table 1.
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Spontaneous Baroreflex Sensitivity Analyses
HR and MAP during the total resting period for 3 days (~135 min, n = ~81,000) were used to determine baroreflex sensitivity in each mouse at rest. Because spontaneous change in MAP and consecutive change in HR were observed at 5-15 cycles/min (4-12 s/cycle) as shown in Figs. 3 and 4, the relation betweenMAP and the consecutive HR from the
baselines was analyzed every 4 s using a cross-correlation function given in the following formulas (1)
![R(t)=f[<IT>&Dgr;x</IT>(<IT>t+&Dgr;t</IT>)<IT>,&Dgr;y</IT>(<IT>t</IT>)]](/content/vol284/issue3/fulltext/H939/img001.gif)
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t = 0.6 s) in response to HR change,
f is function, and d is derivative. The
(t) and 
(= 4 s). The detailed
numerical analyses are given in the APPENDIX. A regression equation was determined from the pooled data during rest in each mouse.
The slope of the regression line was used as an index of the
spontaneous baroreflex sensitivity.
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Drug-Induced Baroreflex Sensitivity Analyses
The baroreflex sensitivity was also determined from sigmoid the response of HR to MAP altered by intra-arterial administration of SNP or PE. Briefly, after we confirmed that the baselines of MAP and HR were 15 or 30 µg/kg (90 µg/ml saline) of SNP and 5 or 10 µg/kg (30 µg/ml) of PE was injected with a 100-µl syringe (Hamilton; Reno, NV) through a bifurcation of a Y-shaped tube (model CMA/12, BAS; Tokyo, Japan) inserted in a catheter for arterial pressure measurement, which was placed in the femoral artery 4-6 days before the experiment. Because no sufficient increase in MAP was obtained at 10 µg/kg of PE in KO mice, an additional experiment at 50 µg/kg of PE (300 µg/ml) was performed. The responses until ~1 s after the injection were not measured because one bifurcation of the Y-shaped tube connected to the pressure transducer was closed during the drug injections into the other bifurcation. Thereafter, MAP and HR responses were recorded and used for drug-induced baroreflex sensitivity analyses.The baroreflex curves expressed as the relationship between MAP and HR
were analyzed with a logistic sigmoid function according to the
following equation (11, 17)
![HR<IT>=&agr;/</IT>[1<IT>+e</IT><SUP><IT>&bgr;</IT>(MAP<IT>−&ggr;</IT>)</SUP>]<IT>+&dgr;</IT>](/content/vol284/issue3/fulltext/H939/img005.gif)
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is the range between the upper and lower plateau,
e is exponential function, 
is a coefficient to calculate
the gain as a function of pressure, 
is the MAP at midrange of the curve (midpoint), and 
is the lower plateau. Each parameter and the
threshold pressure (lowest pressure that products a significant decline
in HR) and the saturation pressure (pressure necessary to achieve
maximal inhibition of HR) were determined by fitting the equation to
minimize the sum of y distance between the experimental data
(HR) and the y value (HR) obtained by substituting
x value (MAP) for the equation.
Statistical Analysis
Values are expressed as means ± SE. The pairwise comparisons in mean and CV values between the KO and WT mice were calculated by using Fisher's least-significant difference test with the post hoc test after confirming the significance with a two-way ANOVA.| |
RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
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Table 1 shows MAP and HR at rest in the WT and KO mice in carotid innervated and denervated conditions. The resting period in both groups was 70-80% of the total measuring period with no significant differences between the groups or between innervated and denervated conditions. In the innervated condition, HR was significantly lower in the KO mice than in the WT mice (P < 0.05), whereas MAP was not significantly different between the groups (P > 0.9). After carotid sinus denervation, MAP increased significantly (P < 0.05) in the WT mice but not in the KO mice (P > 0.4), whereas HR in the KO mice increased significantly (P < 0.001) but not in the WT mice (P > 0.2). In the innervated condition, there were no significant differences in the CV of MAP between the groups, whereas that of HR was twofold higher in the KO mice than that in the WT mice (P < 0.001). After carotid denervation, the CV of MAP increased by twofold in both groups (P < 0.001), whereas the CV of HR in the KO mice decreased to one-half that in the innervated mice (P < 0.001), which was not significantly different from that in the innervated WT mice. There was no significant change in the CV of HR for the WT mice after denervation.
Figure 3 shows typical examples of MAP and HR during the resting period of 16 min in one typical WT mouse (Fig. 3A) and one typical KO mouse (Fig. 3B). Although the variability in MAP was similar between the groups, that in HR was significantly higher in the KO mice than that in the WT mice.
Figure 4, A and B, is enlarged from the parts indicated by closed bars in Fig. 3, A and B, respectively. As shown in Fig. 4, a rise in MAP caused a fall in HR and inversely a fall in MAP caused a rise in HR after a 0.6-s delay.
Figure 5 shows an example of
R(t) between HR and MAP at the given time of
t in a WT mouse, demonstrating a significantly positive or
negative correlation above or below the dotted lines of
P < 0.05, respectively. As summarized in Table 1, the
negative correlation period between HR and MAP was 69% of the
total measuring period in the KO mice, which was significantly >51%
in the WT mice (P < 0.01). On the other hand, the
significant positive correlation period was 4% in the KO mice, which
was significantly <11% in the WT mice (P < 0.05).
After carotid sinus denervation, the negative correlation period
decreased to 40% of the predenervated level in the WT mice
(P < 0.001) and to 20% in the KO mice
(P < 0.001), whereas that of the positive correlation
increased threefold in the WT mice (P < 0.01) and
sixfold in the KO mice (P < 0.01).
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The significant negative correlations were pooled for regression
analyses and the results are presented in Fig.
6A for the WT mice and in Fig.
6B for the KO mice. As summarized in Table 1, the negative
slope of HR/MAP was twofold steeper in the KO mice than that in
the WT mice in the innervated condition (P < 0.001).
After carotid sinus denervation, the negative slope decreased to
one-third that in the innervated condition for the WT mice
(P < 0.001) and to one-sixth in the KO mice
(P < 0.001), and the significant difference between
the groups in the innnervated condition disappeared (P > 0.7). The positive slope was not significantly different between the
groups in the innervated condition, but after denervation it decreased
to 53% of the predenervated value in the WT mice (P < 0.05) and to 30% in the KO mice (P < 0.001) with no
significant difference between the groups (P > 0.9).
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Figure 7 shows the changes in MAP after
the injections of PE and SNP. The increases in MAP by 5 and 10 µg/kg
of PE in the KO mice were 9.3 ± 0.4 and 18.2 ± 1.4 mmHg,
respectively, which were significantly <23.0 ± 1.5 and 28.8 ± 2.7 mmHg in the WT mice, respectively (P < 0.001).
On the other hand, there were no significant differences in vascular
response to SNP between the two groups (P > 0.07).
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Figure 8A shows a typical
example of the relation between MAP and HR after injection of PE and
SNP into a WT mouse with a best-fit sigmoid baroreflex curve generated,
as described above. Figure 8B shows the best-fit curves to
the mean values of the midpoint, threshold, saturation, maximum, and
minimum determined in WT and KO mice. There were no significant
differences in the parameters between the two groups as summarized in
Table 2.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
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In this study, we first chronically implanted catheters in the calponin KO mice and measured MAP and HR under free-moving conditions. The major findings were the following: 1) the variability of HR in the KO mice during rest was twofold higher than that in the WT mice, whereas that in MAP was not significantly different between the two groups; 2) baroreflex sensitivity, determined by the HR response to spontaneous change in MAP, was twofold higher in the KO mice than that in the WT mice; 3) there was no significant difference in the sensitivity determined by intra-arterial administration of the PE or SNP; 4) MAP response to the PE in the KO mice was reduced to one-half that in the WT mice but with no significant difference in the response to SNP; and 5) the higher variability of HR and the higher baroreflex sensitivity in the KO mice disappeared after carotid sinus denervation.
The baroreflex sensitivity was determined from the HR response to
spontaneous change in MAP (Table 1) and from induced change in MAP by
drug injections (Table 2). Recently, the baroreflex sensitivity was
evaluated from the pulse interval response to spontaneous change in
arterial pressure in conscious cats (2), humans (6,
7), and anesthetized mice (25). It was determined that the sensitivity from the slope of the pulse intervals and the
systolic pressure, based on the findings that changes in three or more
consecutive pulse intervals in response to the preceding systolic
arterial pressure were positively correlated. In the present study,
although we failed to measure precisely the systolic and diastolic
pressures because of the damper effect of the measuring system, MAP
fluctuated at the frequency of 5-15 cycles/min, followed by an
almost similar frequency of fluctuation of HR after a short delay time.
When analyzed by a cross-correlation function at 4-s intervals, HR
was negatively correlated with MAP during 51% of the total resting
period in the WT mice and 69% in the KO mice in the innervated
condition. Moreover, after sinus denervation, the percentage period of
the negative correlation was markedly diminished in both groups. In
addition, the baroreflex sensitivity determined by the spontaneous
method in the WT mice agreed well with previously reported findings in
mice by the drug-induced method (13) and spontaneous
method (25). Thus the baroreflex sensitivity by the
spontaneous method in the present study was reliable enough to clarify
the difference in the sensitivity between the WT and KO mice.
In the KO mice, MAP was controlled in such a narrow range as in the WT
mice, whereas the HR variability was significantly higher than that in
the WT mice (Fig. 3 and Table 1), which was adequately explained by the
enhanced spontaneous baroreflex sensitivity in the KO mice (Fig.
6B and Table 1). Moreover, in the KO mice, the negative
correlation period between HR and MAP was 35% longer than that
in the WT mice and the positive correlation period was 50% shorter
(Table 1). In addition, all of these differences between the groups
disappeared after carotid sinus denervation (Table 1). These results
suggest that MAP in the KO mice was more strongly controlled by
baroreflexes than that in the WT mice.
The enhanced baroreflex sensitivity in the KO mice may be associated
with vascular characteristics due to calponin deficiency in the KO
mice. Regarding the molecular aspects of calponin function in the
smooth muscle, Winder and Walsh (26) suggested in a
reconstituted isolated filament system that calponin inhibits
actomyosin ATPase by binding to the actin filament. Takahashi et al.
(23) suggested that calponin reduced the shortening
velocity in the tonic phase of contraction by regulating of
cross-bridge cycling. On the other hand, calponin was reported to
undergo an agonist-induced signal transduction in ferret vascular
smooth muscle (16, 20). Recently, Je et al.
(9) reported that the contractile response to PE was
significantly decreased in the ferret aorta after calponin antisense
treatment, suggesting that calponin facilitates -adrenergic contractions in tonic smooth muscle. Nigam et al. (18)
reported that the calponin-positive rat aorta was slightly but
significantly more sensitive in the contractile response to NE compared
with that in the calponin-negative rat aorta. In the present study, we
confirmed in the KO mice that the vascular response to PE was reduced
to 40-63% of that in the WT mice (Fig. 7).
Together, these results suggest that the impaired
contraction/relaxation functions in the vascular smooth muscle itself
and/or the reduced -adrenergic contractile response to the
sympathetic nervous activity makes MAP unstable in the KO mice and that
the enhanced baroreflex sensitivity compensates well for the
impairments by increasing HR variability.
We hypothesized that baroreceptor denervation in the KO mice would
induce higher fluctuations in MAP than that in the WT mice if the
baroreflexes in the KO mice compensate for the MAP fluctuation due to
impaired contraction/relaxation functions of the vascular smooth muscle
itself. Against our hypotheses, however, there was no higher increase
in the fluctuation of MAP for the KO mice than that for the WT mice
(Table 1). Moreover, we found the vascular response to PE was reduced
(Fig. 7) and that MAP in the KO mice did not increase significantly
after denervation despite the possible increase in sympathetic nervous
outflow, whereas MAP in the WT mice significantly increased (Table 1).
These results suggest that the enhanced baroreflex sensitivity in the
KO mice was a compensatory adaptation to the blunted -adrenergic
response of the vascular smooth muscles to sympathetic nervous activity
elicited by baroreflexes rather than by impaired contraction/relaxation functions of the muscle itself (14, 23).
Matthew et al. (14) reported that the amount of actin was
reduced by 25-50% in smooth muscle in the same line of KO mice used in the present study. The possibility may not be excluded that the
decreased actin filament in the smooth muscle for the KO mice rather
than the absence of calponin was responsible for the reduced vascular
sensitivity to PE. However, no difference in the response to SNP
between the two groups was observed, suggesting that the reduced
sensitivity to PE was more associated with -adrenergic signal
transduction in the smooth muscle than with decreased actin filament.
As shown in Table 2 and Fig. 8, drug-induced baroreflex sensitivity was not significantly different between the WT and KO mice and not identical to the higher spontaneous baroreflex sensitivity in the KO mice (Table 1). There are no known studies explaining the mechanisms. However, the baroreflex sensitivity may vary in various conditions in free-moving animals by efferent control to the cardiovascular center in the brain stem from the higher central nervous system (21). For example, the baroreflex sensitivity was reported to decrease during exercise (3, 4) and after exercise (5) compared with that before exercise. Recently, Kajeker et al. (10) studied the role of rostral ventrolateral medulla neurons in controlling arterial baroreflex sensitivity and reported that GABA signaling in the brain stem increased after a bout of exercise to decrease arterial baroreflex sensitivity, leading to hypotension. Moreover, microinjection of the NO synthetase inhibitor into this area increased and the NO donor SNP reduced sympathetic outflow, perhaps via an inhibitory effect on sympathoexcitatory neurons in the brain stem (28). These results suggest that the enhanced spontaneous baroreflex sensitivity in the KO mice was caused by central modulation to the cardiovascular center in the brain stem and the enhancement was diminished by the administration of the drugs, as in the present study.
As shown in Table 1, the spontaneous baroreflex sensitivity was one-third and one-half of the drug-induced baroreflex gain in the WT and KO mice, respectively, despite the same amplitude of change in MAP (± ~5 mmHg) from the baseline (Fig. 8 and Table 2). To determine spontaneous baroreflex sensitivity, MAP and HR were analyzed every 4 s, much shorter than the 30 s to determine drug-induced baroreflex sensitivity, a period for HR and/or MAP to return to the baseline after the injections. However, the spontaneous changing rate of MAP was 1-7 mmHg/s, identical to that of drug-induced MAP of 1-8 mmHg/s, suggesting that baroreflex sensitivity in both methods was determined from the HR response similar to the changing rate of MAP. The discrepancy in the baroreflex sensitivity between the two methods may be due to the difference in the regression analyses: a linear regression (spotaneous) and a curvilinear regression (drug induced). In the present study, we found the spontaneous baroreflex sensitivity in the KO mice was twofold higher than that in the WT mice.
The reason for intra-arterial injection of SNP in the present study was because in preliminary experiments in KO mice, HR increased immediately after the intravenous injection of SNP before MAP started to decrease. The precise mechanism for this phenomenon in the KO mice is unclear. However, the high concentration of SNP in circulating blood after a bolus injection into the central vein may modulate baroreflex sensitivity in the brain stem (28) or affect the pacemaker of the heart through direct or indirect effects. Although this immediate response of HR was not observed after intravenous injection of PE, the intra-arterial injection of PE was performed to standardize the procedure.
In summary, the vascular -adrenergic response was impaired in the KO
mice. Although there was no significant difference in the drug-induced
baroreflex sensitivity between the WT and KO mice, the enhance
spontaneous baroreflex sensitivity and the higher frequency of negative
correlation between MAP and HR in the KO mice suggested that the
baroreflex may work as a compensatory adaptation to the impairment of
the vascular -adrenergic response. Thus calponin may play an
important role in controlling MAP by increasing the vascular
-adrenergic response to sympathetic nervous activity.
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APPENDIX |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
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![R(i)=<FENCE> <LIM><OP>∑</OP><LL><IT>i=i</IT></LL><UL><IT>i+n−1</IT></UL></LIM> <IT>&Dgr;X<SUB>i+&Dgr;i</SUB>·&Dgr;y<SUB>i</SUB>− </IT><FR><NU>1</NU><DE><IT>n</IT></DE></FR> <LIM><OP>∑</OP><LL><IT>i=i</IT></LL><UL><IT>i+n</IT></UL></LIM> <IT>&Dgr;X</IT><SUB><IT>i+&Dgr;i</IT></SUB><IT>·</IT><LIM><OP>∑</OP><LL><IT>i=i</IT></LL><UL><IT>i+n</IT></UL></LIM> <IT>&Dgr;y<SUB>i</SUB></IT></FENCE><IT>/</IT>[(<IT>n−</IT>1)<IT>S<SUB>x</SUB> · S<SUB>y</SUB></IT>]](/content/vol284/issue3/fulltext/H939/img008.gif)
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i is the lag number for 0.6 s (= 6), and
n is the data number every 4 s to calculate
R(i) (= 40).
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ACKNOWLEDGEMENTS |
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The authors thank J. Itoh for technical assistance in developing a computer program to collect data. We also thank the staff of the Department of Sports Medicine, Shinshu University School of Medicine for helpful comments and invaluable discussions on this study.
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FOOTNOTES |
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This work was supported in part by grants from the Ministry of Education, Science, Sports, and Culture of Japan and also supported by Ground-based Research Announcement for Space Utilization from the Japan Space Forum.
Address for reprint requests and other correspondence: H. Nose, Dept. of Sports Medicine, Shinshu Univ. School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan (E-mail: nosehir{at}sch.md.shinshu-u.ac.jp).
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.
First published November 14, 2002;10.1152/ajpheart.00610.2002
Received 16 July 2002; accepted in final form 12 November 2002.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
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