Journal of Applied Physiology Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 86: 709-719, 1999;
8750-7587/99 $5.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Osada, T.
Right arrow Articles by Iwane, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Osada, T.
Right arrow Articles by Iwane, H.
Vol. 86, Issue 2, 709-719, February 1999

Reduced blood flow in abdominal viscera measured by Doppler ultrasound during one-legged knee extension

Takuya Osada1, Toshihito Katsumura1, Takafumi Hamaoka1, Shigeru Inoue1, Kazuki Esaki1, Ayumi Sakamoto1,2, Norio Murase1,2, Junichi Kajiyama2, Teruichi Shimomitsu1, and Hisao Iwane1,dagger

1 Department of Preventive Medicine and Public Health, Tokyo Medical University, Tokyo 160-8402; and 2 Tokyo Metropolitan Health Promotion Center, Tokyo 160-0021, Japan


    ABSTRACT
Top
Abstract
Introduction
Methods
Results
Discussion
References

The redistribution of blood flow (BF) in the abdominal viscera during right-legged knee extension-flexion exercise at very low intensity [peak heart rate (HR), 76 beats/min] was examined by using Doppler ultrasound. While sitting, subjects performed a right-legged knee extension-flexion exercise every 6 s for 20 min. BF was measured in the upper abdominal aorta (Ao), right common femoral artery (RCFA), and left common femoral artery (LCFA). Visceral BF (BFVis) was determined by the equation [BFAo - (BFRCFA + BFLCFA)]. A comparison with the change in BF (Delta BF) preexercise showed a greater increase in Delta BFRCFA than in Delta BFAo during exercise. This resulted in a reduction of BFVis to 56% of its preexercise value or a decrease in flow by 1,147 ± 293 (±SE) ml/min at the peak workload. Oxygen consumption correlated positively with Delta BFAo, Delta BFRCFA, and Delta BFLCFA but inversely with Delta BFVis during exercise and recovery. Furthermore, BFVis (% of preexercise value) correlated inversely with both an increase in HR (r = -0.89), and percent peak oxygen consumption (r = -0.99). This study demonstrated that, even during very-low-intensity exercise (HR <90 beats/min), there was a significant shift in BF from the viscera to the exercising muscles.

abdominal visceral blood flow; dynamic knee extension-flexion exercise; pulmonary oxygen consumption; Doppler ultrasound


    INTRODUCTION
Top
Abstract
Introduction
Methods
Results
Discussion
References

SPLANCHNIC CIRCULATION has been described as the "blood giver of circulation" and is believed to play a major role in overall cardiovascular regulation (33). Several investigations of splanchnic and renal blood flow (BF) during stressful conditions, such as exercise, have been conducted in humans. It has been reported that the splanchnic blood pool decreases in volume during exercise (4, 6, 16, 64), and splanchnic BF is reduced in proportion to the relative cardiovascular stress, or relative maximal oxygen consumption (VO2 max) (48, 49, 50). Grimby (23) observed a decrease in renal BF as well as splanchnic BF during supine ergometer exercise. Previous studies have also showed that splanchnic BF and renal BF decrease in a steep linear fashion at exercising heart rates (HRs) between 90 and 200 beats/min (12, 23, 49, 50, 52, 54). However, a reduction in splanchnic BF during very-low-intensity exercise, with a HR of <90 beats/min, has yet to be reported. In addition, there have been no reports on noninvasive estimation of BF redistribution in the abdominal viscera in exercising humans.

Previous studies that measured human splanchnic BF during exercise have used various dye-dilution techniques based on the Fick principle (7, 47, 49), but this method has many limitations for clinical usage. Technological developments in Doppler ultrasound have produced a noninvasive technique for measurement of flow velocity in blood vessels. Validation of this technique has been demonstrated by the thermodilution technique (43), magnetic resonance imaging (67), and plethysmography (35, 61) in human studies, and by electromagnetic flow measurements in animal studies (9, 24, 39). The measurement of BF in humans by using Doppler ultrasound has been accomplished in several large blood vessels located deep in the abdominal cavity (2, 31, 32, 39, 40, 42, 60). Qamar and Read (42) observed a reduction of BF in the superior mesenteric artery immediately after treadmill exercise. A significant reduction in portal venous flow was also observed after ~14 metabolic equivalents of maximal treadmill exercise (31). These results support the concept that BF is redistributed from the abdominal viscera to the working muscles during exercise. However, these results do not directly reflect the concept that BF in abdominal viscera (including the celiac, superior mesenteric, inferior mesenteric, and renal arteries) is redistributed to the working muscles during exercise.

The use of Doppler ultrasound to measure splanchnic BF in small abdominal vessels during exercise offers many advantages, but such measurement also faces several technical limitations, including anatomic variations between subjects, interference from intestinal gas, subcutaneous fat tissue, and body movement. For example, measurements of BF in the inferior mesenteric artery and in each of the two renal arteries have proved to be too difficult because of interference from intestinal gas. Thus, transabdominal sonography may not be completely accurate in detecting quantitative flow parameters in splanchnic arteries (13).

To overcome these limitations, visceral BF (BFVis) was determined by measuring the regional flow patterns in the upper abdominal aorta (Ao) and in each of the two common femoral arteries (CFAs) during one-legged knee-extension exercise, which allowed greater control over body movement. BF in the upper abdominal Ao, right common femoral artery (RCFA), and left common femoral artery (LCFA) were defined as BFAo, BFRCFA, and BFLCFA, respectively. BFVis was determined from the equation BFVis = [BFAo - (BFRCFA + BFLCFA)].

The purpose of this study was to investigate noninvasively the redistribution of BF in the abdominal viscera by using Doppler ultrasound during low-intensity, one-legged knee extension-flexion exercise.


    METHODS
Top
Abstract
Introduction
Methods
Results
Discussion
References

Subjects

Eighteen healthy, untrained subjects (all men), who had no prior history of cardiovascular disease, gastrointestinal disease, or anemia, were studied. The subjects' mean (range in parentheses) age, height, and weight were 29 yr (range 20- 38 yr), 170 cm (159-178 cm), and 67 kg (59-73 kg), respectively. The subjects' mean (range) whole body VO2 max was 41 ml · kg-1 · min-1 (32-46 ml · kg-1 · min-1) and was measured by using breath-by-breath gas analysis during a cycle-ergometer ramp protocol. All of the subjects were informed of the nature, purpose, and risks involved in the study before giving their written consent to participate.

Peak Pulmonary Oxygen Consumption (VO2 peak)

Pulmonary VO2 peak was measured by using a breath-by-breath gas analyzer (Aero monitor AE-280, Minato Medical Science, Osaka, Japan) and was determined during a graded (1-Hz) exercise protocol of right-legged knee extension-flexion (flexion was an eccentric contraction of the quadriceps against a load), modified from Andersen et al. (3). Subjects performed the leg extension-eccentric flexion until exhaustion. Peak exercise was determined at the point of exhaustion when the 1-Hz knee extension-flexion could not be performed without involving the lumbar muscle groups. Involvement of these muscle groups correlated with a rapid change in the oxygen consumption (VO2) slope. Room temperature, relative humidity, and atmospheric pressure during the experiment were ~25°C, 40%, and 760 mmHg, respectively.

Exercise Model and Protocol

All subjects initially participated in one practice session to familiarize themselves with the knee extension-flexion exercise protocol. The right knee extension-flexion (flexion was an eccentric contraction of the quadriceps against a load) exercise was performed with the subjects' hips fixed at a 100° angle in a sitting position, with the use of a specially designed Meiko-100 Knee-Extension Ergometer (Meiko, Tokyo, Japan). Knee extension was performed at knee angles between 90 and 160°, with the foot and ankle secured to an arm rod. The muscle groups involved in the extension-flexion exercise included the rectus femoris and the vastus medialis and lateralis (3). After a 10-h fast, subjects underwent testing and performed the knee extension-flexion exercise at a rate of 10 cycles/min for 20 min. Each cycle consisted of three phases: phase 1, a 1-s knee extension from ~90 to 160°; phase 2, 1-s knee flexion, returning the leg to the 90° resting position; and phase 3, a 4-s relaxation period. Knee extension-flexion was performed against loads of 6.5, 16.5, 31.5, and 46.5 kg, which corresponded to the intensities of 2.1, 5.4, 10.3, and 15.2 W, respectively, averaged over 6 s. For the first 5 min of the exercise protocol, the intensity was set at 2.1 W and was then increased every 5 min to 5.4, 10.3, and 15.2 W, respectively.

A 5-min recovery period followed the 20-min exercise bout. VO2 was measured continuously, by using breath-by-breath gas analysis, during the preexercise, exercise, and recovery periods. Arterial blood pressure (BP) was monitored each minute (STBP-780B, Colin, Aichi, Japan) by using a sphygmomanometer blood pressure cuff tourniquet placed on the upper part of the left arm. HR was measured each minute by electrocardiography (Fukuda Denshi, Tokyo, Japan). Percent VO2 peak was calculated from the equation (VO2/VO2 peak × 100).

BF Measurements

Doppler instrument. BF was determined by using a Doppler instrument (SONOS 1500, ultrasound-imaging system HP 77035A, Hewlett-Packard, Tokyo, Japan) which consisted of a real-time, two-dimensional, ultrasonic imager with a pulsed-Doppler flowmeter and a videotape recorder (video cassette recorder AG-7350-P, Panasonic, Tokyo, Japan).

Location of measured vessel. BF was measured at 1) the upper abdominal Ao (1 cm above the celiac artery bifurcation), 2) the RCFA (exercising leg), and 3) the LCFA (nonexercising leg), below the inguinal ligaments, 1 cm above the bifurcation to the superficial and deep femoral arteries. BFs in the Ao, RCFA, and LCFA were defined as BFAo, BFRCFA, and BFLCFA, respectively. One measurement of BF cycle for the Ao, RCFA, and LCFA was determined within the time frame of 1 min (Fig. 1). The three arterial BFs were measured five times preexercise, three times at each exercise intensity, and four times during recovery. Measurements of BFRCFA, BFLCFA, and BFAo were performed during each of the 4-s relaxation phases after the knee extension-flexion phases. An accurate, continuous Doppler wave of Ao and LCFA was obtained during the relaxation phase.


View larger version (40K):
[in this window]
[in a new window]
  		Fig. 1.   Schematic anatomic illustration of the 3 measured vessels. Blood flow (BF) measurements were conducted in the upper abdominal aorta (Ao) above the celiac artery bifurcation and bilateral femoral arteries (right common femoral artery and left common femoral artery, RCFA and LCFA, respectively). BF of abdominal viscera (BFVis), including splanchnic and renal arteries, was calculated by subtracting bilateral common femoral arterial flow (BFRCFA + BFLCFA) from BFAo.

Two types of probes were used in this study, a 2.7- or 3.5-MHz curved linear probe and a 5.5- or 7.5-MHz linear probe (Hewlett-Packard), each having an automatic switching system known as "frequency agility." The 2.7- or 3.5-MHz probe for deep vessels (Ao) used the 2.7-MHz setting for measuring velocity and the 3.5-MHz setting for higher sensitivity vessel imaging. The 5.5- or 7.5-MHz probe used the 5.5-MHz setting for velocity measurements and the 7.5-MHz setting for imaging of the superficial vessels (femoral arteries).

Measurement of vessel diameter. Two-dimensional-imaging echography analysis was carried out with a duplex scanner fitted with a 3.5-MHz probe setting at the BFAo measuring site and with a 7.5-MHz probe setting at both the BFRCFA- and BFLCFA-measuring sites. Doppler probes at different frequencies were used to measure the diameters of the Ao and CFAs, respectively. The vessel of the Ao is located ~10 cm below the substernal surface, and the CFA is ~2 cm from the surface. The lower frequency (3.5 MHz) Doppler signal provides good penetration for detection of deep vessels and imaging of the vessel for diameter measurements. Therefore, a 3.5-MHz setting probe was used to obtain accurate imaging of the vessel diameter for the Ao. On the other hand, a probe setting with a high-frequency (7.5 MHz) Doppler signal was used to detect superficial vessels, with diameters up to 10 mm, for good axial resolution. Therefore, the 7.5-MHz probe setting was used for measuring and imaging the CFA vessel. The inner diameters of the vessel during systolic and diastolic phases were measured in longitudinal section (Fig. 2). Mean vessel diameter was calculated as (systolic diameter + diastolic diameter)/2.


View larger version (112K):
[in this window]
[in a new window]
  		Fig. 2.   Two-dimensional echography and Doppler signal of upper abdominal Ao (left) and RCFA (right) in exercising leg (longitudinal axis). Top: 2-dimensional echography of upper abdominal Ao above the celiac artery bifurcation (left) and RCFA (right). Middle: Doppler signal of each vessel flow at rest (preexercise). Bottom: Doppler signal of each vessel flow on relaxation phase after knee extension-flexion exercise at 15.2 W. Signals at preexercise appear to show a high-resistance pattern and to become low resistance after mild exercise. This indicates an increase in diastolic velocity during relaxation phase.

Measurement of velocity. Velocity analysis by pulsed Doppler flowmetry was carried out with a 2.7-MHz probe setting at the BFAo measurement site and with a 5.5-MHz probe setting at both the BFRCFA- and BFLCFA-measurement sites. Blood vessels located deep below the surface characteristically have a fast-flow velocity, and shallow vessels characteristically have a low-flow velocity; therefore, low-frequency (2.7 MHz) and high-frequency (5.5 MHz) probe settings, respectively, were utilized.

A real-time imaging system, without aliasing, was used to visualize the three arterial vessels and allowed the placement of the Doppler sample volume within the lumen of these vessels to obtain the Doppler shift signals. The sample volume was kept at the center of the lumen and adjusted to cover the width of the vessel and the blood velocity distribution. Mean blood velocity was calculated by integration of the outer envelope of the maximal velocity values in the flow profile (30) and was determined as the mean value of three or four successive cardiac cycles for each vessel. An ultrasound beam angle of insonation of <60° (the angle between the ultrasound beam and the long axis of the vessel) was used, because high angles affected the accuracy of the velocity calculation (20, 21).

Calculation of BF. Mean cross-sectional area was determined as pi  × (mean vessel diameter)2/4. BF was calculated as the product of mean blood velocity and mean cross-sectional area as (mean blood velocity × mean cross-sectional area). Changes in BF between preexercise and exercise, or between preexercise and recovery, were defined as Delta BF.

Determination of BFVis. BFVis in the abdomen preexercise, during the knee extension-flexion exercise, and during the 5-min recovery was calculated by subtracting the sum of BFRCFA and BFLCFA from BFAo, as shown by the equation BFVis = [BFAo - (BFRCFA + BFLCFA)].

Statistics

Values are presented as means ± SE. Statistical comparisons within each measured group parameter were performed by one-way ANOVA for repeated measurements, and the difference from the preexercise value was located by Scheffé's post hoc comparisons. An independence between Delta BF and VO2, percentage of preexercise BFVis and HR, and percentage of preexercise BFVis, and percentage of VO2 peak were evaluated by using linear regression analysis. A P < 0.05 level was chosen as significant.


    RESULTS
Top
Abstract
Introduction
Methods
Results
Discussion
References

Values for systolic blood pressure (SBP), diastolic blood pressure (DBP), HR, VO2, and percentage VO2 peak for preexercise, each exercise intensity, and recovery are summarized in Table 1. VO2 peak, as determined by the incremental knee extension-flexion exercise protocol, was 13.1 ± 0.4 ml · kg-1 · min-1. The change in percentage VO2 peak between preexercise and the peak workload (15.2 W) was almost a twofold increase. A significant change in SBP was observed at 15.2 W compared with the preexercise value, whereas DBP was constant throughout the experiment. Mean HR increased significantly from 70 ± 3 to 76 ± 3 beats/min at 5.4 and 15.2 W, respectively. The values for BF during preexercise, exercise, and recovery are summarized in Table 2; the values in parentheses are the percentage of the preexercise value. At rest, BFAo was eightfold higher than BFRCFA and BFLCFA. No significant difference was seen between preexercise BFRCFA and BFLCFA. During the first 5 min of exercise at 2.1 W, BFAo increased significantly to 120% of its preexercise value and reached 147% at a workload of 15.2 W. BFRCFA (exercising leg) increased to 330% of its preexercise value at 2.1 W and further increased to 660% at 15.2 W. There was a relatively small increase in BFLCFA (nonexercising leg) to 140% of its preexercise value at 2.1 W and reached 157% at 15.2 W. A reduction in BFVis to 80% of its preexercise value was obtained at 2.1 W, and thereafter BFVis decreased by ~10% at each of the later workloads. VO2 increased to 140% of its preexercise value at 2.1 W and reached 200% at 15.2 W (Table 2 and Fig. 3).

                              
View this table:
[in this window]
[in a new window]
  		Table 1.   Measurement of blood pressure, HR, VO2, and %VO2 peak preexercise, at each exercise intensity, and during recovery


                              
View this table:
[in this window]
[in a new window]
  		Table 2.   Preexercise blood flow (BF) values and changes in blood flow at each exercise intensity and recovery



View larger version (35K):
[in this window]
[in a new window]
  		Fig. 3.   Changes in BF (Delta BF) (top) of BFAo, RCFA, LCFA, and BFVis and oxygen consumption (VO2; bottom) preexercise, during exercise, and during recovery. BFVis was calculated by subtracting bilateral leg flow from BFAo and was plotted as average of measurement time point in the 3 vessels. Measurement points are indicated by solid bars at bottom. Values are means ± SE.

A positive correlation was observed between VO2 (during exercise and recovery) and Delta BF (BFAo, BFRCFA, and BFLCFA) at each measurement site (Fig. 4). VO2 correlated inversely with Delta BFVis during exercise and recovery (P < 0.001). A decrease in BFVis (% of preexercise value) was proportional to an increase in HR during exercise. The regression lines reflect the mean value of y (% of preexercise BFVis) for a given value of x (HR) from the regression equation y = -3.597x + 327.2 (r = -0.89).


View larger version (27K):
[in this window]
[in a new window]
  		Fig. 4.   Pooled data showing relationship between pulmonary VO2 and Delta BF during exercise and recovery phases. Delta BFVis (black-triangle; P < 0.001) decreased with an increase in VO2, while Delta BFAo (; P < 0.001), Delta BFRCFA (bullet ; P < 0.001), and Delta BFLCFA (open circle ; P < 0.01) increased significantly with an increase in VO2. Plots represent average of data obtained from all 18 subjects during preexercise, exercise, and recovery.

A decrease in BFVis (% of preexercise value) was proportional to an increase in %VO2 peak during exercise. The regression lines reflect the mean value of y (% of resting BFVis) for a given value of x' (%VO2 peak) from the regression equation y = -1.580x' + 145.13 (r = -0.99).

The values obtained in the preliminary test for each vessel diameter during exercise (2.1, 5.4, 10.3, and 15.2 W), at 1 min of recovery, and at 2-5 min of recovery are shown in Table 3. These diameters remained constant throughout the exercise protocol and recovery.

                              
View this table:
[in this window]
[in a new window]
  		Table 3.   Diameter values in each vessel at preexercise, at each exercise intensity, and during recovery in preliminary test

Intraobserver Variability

Before the experiments, intraobserver variability for this operator was determined for 18 subjects over a period of 30 min. At rest, the coefficients of variation determined for blood vessel diameter and mean blood velocity in the Ao, RCFA, and LCFA for three repeated diameter measurements were 3.9 ± 2.5, 2.3 ± 1.2, and 2.8 ±0.5%, respectively, and for three repeated mean blood velocity measurements, were 3.6 ± 0.6, 3.2 ± 0.6, and 3.1 ± 0.3%, respectively.


    DISCUSSION
Top
Abstract
Introduction
Methods
Results
Discussion
References

Decreased BFVis During Exercise

The major finding in this study was that BFVis significantly decreased even at HR <90 beats/min (the magnitude of decrease in BFVis was significant during exercise). Furthermore, the reduction in BFVis is closely related to VO2 when expressed as the relative workload (%VO2 peak).

In humans, it has been well demonstrated that splanchnic BF decreases during severe graded exercise (4, 16, 64). It is well accepted that increased sympathetic nervous activity is responsible for the redistribution of BF away from the splanchnic area, the kidneys, and the resting skeletal muscles to the working muscle. The increase in BF and oxygen delivery to working muscles is caused not only by an increase in cardiac output but also through a redistribution of cardiac output. At rest, splanchnic organs receive a greater percentage of cardiac output than any other region. Despite the relatively high BF, splanchnic organs consume relatively less oxygen, which enables splanchnic BF to be markedly reduced without sacrificing the local oxygen demand during exercise.

As previously mentioned, an increase in HR and the degree of visceral vasoconstriction are both a function of the relative work intensity. This study observed a strong relationship between an increase in HR and a decrease in splanchnic BF during exercise. Both splanchnic and renal BF show the same relationship to HR during exercise (23). Unlike responses to exercise in hot or cool environments, the reduction in splanchnic BF during heat stress is unrelated to pulmonary VO2 max but is closely related to HR (52). Depending on the stress levels of humans, increases in HR parallel a proportional increase in vasomotor activity in visceral organs (46). Furthermore, splanchnic BF has been shown to decrease at HR even below 60 beats/min during lower-body negative pressure (53) and during heat stress (51). The reduction ratio in both these conditions did not vary. Clausen et al. (12) demonstrated that hepatic BF is reduced to ~30-40% of its resting value during arm and leg exercises. Rowell (46, 48) indicated that no matter what type of stress is applied to a subject, the slopes of the lines relating changes in splanchnic BF to HR are always statistically the same. It has also been demonstrated that a reduction of splanchnic BF (48) and renal BF (23) during exercise increases as a function of the relative workload expressed as the %VO2 max. It was shown that BF to the kidney decreased to 55-65% of its resting value during supine cycling exercise at intensities 35-70% of VO2 max (23).

A reduction of BFVis during one-legged knee extension-flexion exercise at a HR of <90 beats/min has yet to be reported. This study found BFVis decreased steeply between its preexercise level (mean HR, 67 beats/min; VO2, 3.7 ml · kg-1 · min-1) and the peak exercise intensity (mean HR, 76.2 beats/min; VO2, 7.13 ml · kg-1 · min-1). The relationship between BFVis and HR observed in this study (knee extension-flexion exercise) is not in agreement with the relationship of splanchnic BF and HR, as demonstrated by previous studies that used a cycle-ergometer model (Fig. 5). However, when the same BFVis data are expressed as a function of percent VO2 peak, the slope is similar to the one determined for splanchnic BF and percent VO2 max by Rowell et al. (49) as shown in Fig. 6. The disparity seen in the relationship between BFVis and HR (Fig. 5) could be attributed to the differences in the exercise models and intensity.


View larger version (33K):
[in this window]
[in a new window]
  		Fig. 5.   Relationship between heart rate (HR) and %preexercise abdominal BFVis during dynamic one-legged knee extension-flexion exercise. Exer, exercise; LBNP, lower-body negative pressure; RBF, renal blood flow. Comparison of linear decrease in BF, as plotted against HR, at exercise intensities that produce between 90 and 200 beats/min. This figure is modified from that described by Rowell (46). %Preexercise BFVis was correlated inversely with HR. Regression lines in this study are for mean value of y (%preexercise BFVis) for a given value of x (HR) from the regression equation y = -3.59x + 327.2 (r = -0.89).


View larger version (20K):
[in this window]
[in a new window]
  		Fig. 6.   Relationship between %preexercise abdominal BFVis and %oxygen consumption (VO2)/peak VO2 (VO2 peak) during dynamic one-legged knee extension-flexion exercise. Regression lines in this study are for mean value of y (%preexercise BFVis) for a given value of x' (%VO2 peak) from regression equation y = -1.58x' + 145.1 (r = -0.99). Data from this study follow relationship similar to that obtained by Rowell et al. (49, 50).

Mechanisms contributing to the redistribution of BFVis, including vasodilator metabolite products and chemo- and mechanoreflexes, could also account for the differences between knee extension-flexion exercise and cycle-ergometer exercise. During the knee extension-flexion exercise, HR and VO2 increased by <10 beats/min and 4.0 ml · kg-1 · min-1, respectively. This fact suggests that an increase in the BF to the exercising leg was redistributed from BFVis at a relatively lower cardiac output and a corresponding low HR. Delta BFRCFA was greater than Delta BFAo during exercise. Thus, at a lower cardiac output during low-intensity exercise, the redistribution of BF could be attributed to an initial decrease in BFVis. It was concluded that decreased BFVis plays an important role in increasing BFRCFA to the working muscles of the leg at either low HR or low cardiac output during low-intensity exercise in humans. The low HR and VO2 during the exercise protocol suggests that a proportional small muscle mass was utilized and/or a low-intensity activity.

In working muscles, the increased sympathetic drive could have been countered by the effect of local vasodilator metabolites (25). Furthermore, a reduction in the BFVis caused by the abdominal organs' vascular constriction may have been mediated by chemoreflexes originating in the working muscles and/or local vasodilator metabolites.

With regard to the redistribution of splanchnic BF during exercise, a number of mechanisms have been suggested for exercise-induced splanchnic vasoconstriction (48). Splanchnic and renal BF is regulated by 1) neural control through sympathetic vasoconstrictor nerves (11), 2) reflex control through baroreceptors (9, 37) and chemoreceptors (34), 3) hormonal secretion (31), 4) muscle metabolites, and 5) thermoregulation (46). It has been suggested that the mechanism of BF redistribution is caused by the action of these factors in varying degrees. Increased sympathetic nervous activity in the working muscle group is accompanied by a proportional increase in sympathetic vasoconstriction that, in humans, decreases blood to the visceral organs during exercise. Thus sympathetic nervous activity is increased predominantly in the heart and viscera. It has been suggested that sympathetic nervous activity increases in visceral organs rather than in muscles during dynamic exercise. Both epinephrine and norepinephrine can cause marked changes in splanchnic BF (5, 22). However, the low-intensity exercise in this study would have little effect on increasing plasma cathecholamines (55). Reflexes originating from the working muscle are also thought to play an important role in regulating BF (46, 59). In an animal study, mechanoreceptors showing group III afferent nerve activity during muscular contraction were found to cause vasoconstriction of visceral arteries (63). Furthermore, muscle chemoreflex (i.e., detection of muscle metabolites, such as lactic acid and H+) has been shown to cause renal vascular constriction (38). These two studies suggest that neural signals from the working muscles may play an important role in the redistribution of BF away from abdominal viscera during exercise.

Changes in BF and VO2

It has been demonstrated that both pulmonary VO2 and muscle VO2 increased linearly with the work intensity (from no load to 50 W) during a one-legged dynamic knee-extensor exercise (3). Leg BF at the contraction site also increased linearly with an increasing work rate (3, 27, 45, 56). There appeared to be a linear relationship between pulmonary VO2 or muscle VO2 and BF in the leg during this exercise protocol. The close relationship between changes in VO2 and changes in regional BF also holds true for cycle-ergometer findings in exercise (56). Splanchnic (48) and renal (23) BF decline in relation to absolute VO2 normalized for body weight and in relation to relative VO2 as %VO2 max. Thus both splanchnic and renal BF are reduced in close proportion to the relative intensity of exercise when expressed as %VO2 max.

In this study, Delta BFAo, Delta BFRCFA (exercise site), and Delta BFLCFA (nonexercise site) increased linearly (P < 0.001, P < 0.001, and P < 0.01, respectively) with an increasing VO2, whereas Delta BFVis decreased linearly (P < 0.001) with an increasing VO2, which had a range from 3.74 to 7.13 ml · kg-1 · min-1 (Fig. 4). These results are in agreement with previous findings which have also demonstrated that a positive linear relationship exists between regional BF of the leg and VO2. With the use of Doppler ultrasound, the conclusion can be reached that decreased BFVis is closely related to oxygen demand even during very-low-intensity exercise (HR < 90 beats/min) (Fig. 5).

Methodological Considerations

Reliability of BF measurements. Blood vessel diameters of the Ao, RCFA, and LCFA were measured preexercise by using two-dimensional imaging echography (Fig. 2). It was considered that measurement of the diameter of RCFA in an exercising leg during a short relaxation period of 4 s may not be accurate. However, in preliminary tests, the diameter of the three arteries was measured in all 18 subjects (preexercise), during knee extension-flexion exercise, and during recovery. The diameter values obtained preexercise, at each exercise intensity, at 1 min of recovery, and at 2-5 min of recovery were found not to have significantly changed (Table 3). It was concluded that the diameter of the three arteries remained constant in these subjects during this exercise protocol; this is in agreement with previous BF studies that used Doppler ultrasound (43, 58). Previous studies observed that the diameter of CFA did not change significantly during incremental cycle-ergometer exercise (27, 30). Rådegran (43) also demonstrated that the mean vessel diameter of the femoral artery in the exercising leg was constant during single 1-Hz knee-extension exercise at rest and at 30 and 50 W. Shoemaker et al. (58) found the brachial artery diameter during dynamic handgrip exercise did not differ from rest, nor did the diameter change from day to day. Walløe and Wesche (66) and Eriksen et al. (14) reported BF in CFA on the basis of the resting diameter value of the CFA instead of the diameter obtained during rhythmic leg exercising. Therefore, in the present study, the cross-sectional inner vessel diameter of the Ao and each of CFAs measured during rest was deemed acceptable to use for the BF calculation during exercise. Although Shoemaker et al. (57) found no change in brachial artery diameter at a lower work rate, they did see vessel dilation at a higher work rate. These data suggest that dilation might be a function of accumulation of vasoactive metabolites. In an additional study, flow-mediated vasodilation after ischemia was demonstrated by Plotnick et al. (41) in subjects pretreated with antioxidant vitamins C and E. This demonstrates an important relationship between BF and oxidative factors.

Coefficients of variation for mean blood velocity and HR during exercise and recovery. The coefficients of variation for mean blood velocity of each vessel and for HR at each workload and during recovery are shown in Table 4. The coefficient of variation for HR during the first minute of recovery was 5.1, which was higher than that at 2-5 min of the recovery phase. During the first minute of recovery, HR returned quickly to its preexercise level.

                              
View this table:
[in this window]
[in a new window]
  		Table 4.   Coefficient of variation for mean blood velocity in each BF, and for HR during exercise at each intensity and at 2-5 min of recovery

From these data, it was concluded that mean blood velocity and HR remained steady during the measurement of the BF cycle of three major arteries within a 1-min period, resulting in a coefficient of variation of <5%. Blood velocity and HR measurements obtained from three arterial BF measurements at each exercise workload and during the 2-5 min during recovery did not change significantly. This finding suggests that the formula used to calculate BFVis was valid.

Validation of BF Value at Resting Level

Upper abdominal aorta above the celiac artery bifurcation. In the present study, the values for the resting diameter, cross-sectional area, and BF of the upper abdominal aorta were 16.5 ± 0.27 mm, 2.15 ± 0.07 cm2, and 3,509 ± 155 ml/min, respectively. The values for resting diameter and cross-sectional area from this study are similar to those measured by Gabriel and Kindermann (18) (15.5-17.6 mm, and 1.88-2.43 cm2, respectively). Using Doppler ultrasound, Nimura et al. (40) previously reported the BF values of the upper abdominal aorta and the sum total BF of the celiac, superior mesenteric, and both renal arteries to be 2,470-3,246 and 2,450-3,549 ml/min, respectively. These values are similar to the measurement of 3,509 ± 155 ml/min made in the present study.

CFA. In the present study, the diameters of each CFA were 8.6 ± 0.34 mm in the RCFA and 8.3 ± 0.36 mm in the LCFA. These values are in the same range as the value of 7.5 ± 0.3 mm measured by using angiography (8) and 8.1 ± 0.11 mm measured by duplex Doppler (15). The cross-sectional areas of each CFA obtained in this study were 0.60 ± 0.04 cm2 in the RCFA and 0.56 ± 0.04 cm2 in the LCFA. In this study. the mean blood velocities of both CFAs were 11.9 ± 0.87 cm/s in the RCFA and 11.2 ± 0.86 cm/s in the LCFA. These values are in the same range as the value of 10.2 ± 0.39 cm/s measured by pulsed Doppler (15). In the present study, the BF was 455 ± 25 ml/min in RCFA and 424 ± 27 ml/min in LCFA. These values are in the same range as the values (in ml/min) of 450-886 (1), 301 ± 81 (±SD) (17), and 390 ± 20 (65), as measured by using indicator dilution, and 376 ± 154 (44), 226.5 ± 28.6 (15), 344 (36), and 350-367 (29), as measured by Doppler ultrasound. Furthermore, Ganz et al. (19) reported a value of 383-766 ml/min by using thermodilution, and Vänttinen (62) reported a value of 239 ml/min by using electromagnetic flowmetry. These values were less than those in this study and could be attributed to the differences in the method of measurement, the subject's position during measurement, and local BF per body weight.

Abdominal BFVis. Abdominal BFVis measured in this study was considered the sum of the BF in the celiac, superior mesenteric, inferior mesenteric, both renal, both suprarenal, some lumbar, both gonadal, and both internal iliac arteries. Previous studies (5, 22, 28, 47) have shown that splanchnic BF, including that of the celiac trunk, superior mesenteric, and inferior mesenteric arteries was ~1,500 ml/min, corresponding to 20-30% of cardiac output. The sum of the BF values in the two renal arteries was ~1,000-1,200 ml/min, corresponding to 20% of cardiac output (26). In this study, the preexercise BFVis after fasting was 2,630 ± 153 ml/min. This value is similar to those obtained in previous studies for the sum of the BF in the splanchnic and the two renal arteries. These results suggest that Delta BFVis primarily represents change in BF of the two renal and splanchnic arteries in combination.

Validation of BF Value During Exercise

BF parameters determined by using Doppler ultrasound during one contraction per 6 s of low-level knee-extension exercise have not been reported previously. Thus it was unknown whether or not the BF parameters obtained in this study were valid. However, we were able to estimate the BF resulting from exercise to measure BFRCFA during the relaxation phase but not during the contraction phases of exercise. BFRCFA during exercise obtained in this study were in the same range as femoral arterial BF values during knee-extension exercise (1 Hz) as measured by using Doppler ultrasound (43).

In the present study, measurement of flow was performed only during relaxation. As indicated by Walløe and Wesche (66), there is a significant difference in flow between contraction and relaxation. Recently, Shoemaker et al. (57) and Rådegran (43) have described the need measure flow over the contraction-relaxation cycle. It is possible that resistance is higher during the contraction phase; thus, during the 2-s exercise cycle, BF might be less than during the 4-s relaxation phase (period of measurement for the present study). Therefore, it is possible that BF in other regions may be higher during the muscle contraction phase.

Because of the small degree of error associated with testing large blood vessels, such as the upper abdominal Ao and the CFA, detection was successful in all three vessels during both the preexercise period and during exercise. These vessels could also be measured without the interference of intestinal gas (40), so the sample volume was successfully kept in the center of the vessel lumen. Furthermore, it was only possible to measure BF in the relaxation phase because this phase of exercise requires little overall body movement and provided minimal interference with the Doppler recording.

Limitations

Limitation in the calculated BFVis. BFVis obtained by using formulas in this study include the BF in the lumbar, both gonadal, and both internal iliac arteries. Andersen et al. (3) concluded that, by using the present exercise model, a knee contraction could readily be limited to the quadriceps femoris muscles. We hypothesized that there is no increase in BF to the lumbar and gluteal muscle groups. Thus it was thought that the lumbar and gluteal muscle groups, which receive blood primarily from the lumbar, both gonadal, and both internal iliac arteries, were not active during exercise. Consequently, BF in these arteries was presumed to remain constant during exercise.

Technical limitations for measurement BF velocity. Mean blood velocity obtained in this study was calculated by integration of the outer envelope of the maximal velocity in the vessel flow profile. In general, blood velocity in the center of vessel is relatively faster than the blood near the vessel wall. Furthermore, flat and parabolic velocity profiles are observed during the systolic and diastolic phase in the conduit arterial vessels such as the Ao, carotid, and femoral arteries. In this study, the sample volume was kept at the center of the lumen and was adjusted to cover the width of the vessel and the blood velocity distribution. The measured velocity would have reflected the peak velocity component in the vessel and would have slightly overestimated the BF profile.

Many recent Doppler studies have obtained a more accurate blood velocity from the weighted-mean velocity. This is calculated from the amplitude-weighted, time-and-spatial average on a beat-by-beat basis for each cardiac cycle (43, 57, 58, 61, 66). The Doppler instruments used in this study could not determine the mean blood velocity in this manner.

Comparison as well as limitations of splanchnic BF measurements. The original purpose of this study was to determine BF redistribution in the abdominal viscera, including mainly the splanchnic and renal arteries during exercise, by using Doppler ultrasound. In previous studies, the local BF in these parts of viscera has been most commonly measured using an electromagnetic flowmeter in the open abdomen of an animal (39). Dye-dilution methods have also been used in humans (4, 6, 16, 49, 50, 64). However, the invasive nature and other limitations of these methods does not make them widely applicable to various exercise protocols. Doppler ultrasound is a widely accepted tool for the noninvasive investigation of splanchnic circulation in humans (31, 32, 42). Until now, however, BF has only been researched in the portal vein and in the superior mesenteric artery after exercise. In fact, it is difficult to investigate vessel (particularly, in the inferior mesenteric artery) BF in the abdomen during exercise because of such obstacles as intestinal gas, subcutaneous fat, and body movement. Delahunt et al. (13) indicated that transabdominal sonography is difficult and may not be completely accurate in detecting the quantitative flow parameters in splanchnic arteries. Also, the detection rate in some abdominal arteries (celiac, superior mesenteric, and renal arteries) is less when a person is at rest. The larger size and relative accessibility of the upper abdominal Ao results in a smaller error of measurement of this vessel (40). Gill (20) demonstrated that errors are proportionately greater for smaller vessels in the calculation of blood vessel cross-sectional area. Furthermore, the flow in the abdominal Ao and in each of the CFAs is relatively constant, without marked variation caused by cardiac or respiratory cycles. Therefore, measuring the BF of these vessels during exercise is easier and reliable. One can conclude that the knee-extension exercise used in the present study is suitable for evaluation of BF distribution and can effectively estimate the redistribution of abdominal BFVis.

Conclusions

By using Doppler ultrasound, this study demonstrated that BFVis, including the splanchnic and renal arteries, decreased during very-low-intensity knee extension-flexion exercise at HRs <90 beats/min. The reduction in BFVis occurred at a low-intensity exercise level and was closely related to the relative oxygen demand (relative VO2). A greater increase in BFRCFA compared with BFAo was seen during exercise; this indicates a redistribution of BF from the viscera to the working muscles.


    ACKNOWLEDGEMENTS

The authors thank Professor Bengt Saltin and Dr. Masao Mizuno at the Copenhagen Muscle Research Centre in Denmark; Yukihiro Yamamoto at Hewlett Packard Co., Ltd., Japan; and Kelly F. McGrath for their assistance.


    FOOTNOTES

dagger Deceased.

This study was supported by Tokyo Medical University and The Tokyo Metropolitan Health Promotion Center.

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. §1734 solely to indicate this fact.

Address for reprint requests: T. Osada, Dept. of Preventive Medicine and Public Health, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan (E-mail: tosada{at}tokyomed.ac.jp).

Received 29 April 1998; accepted in final form 1 October 1998.


    REFERENCES
Top
Abstract
Introduction
Methods
Results
Discussion
References

1.   Agrifoglio, G., G. D. Thorburn, and E. A. Edwards. Measurement of blood flow in human lower extremity by indicator-dilution method. Surg. Gynecol. Obstet. 113: 641-645, 1961[Medline].

2.   Alvarez, D., H. Vazquez, J. C. Bai, R. Mastai, D. Flores, and L. Boerr. Superior mesenteric artery blood flow in celiac disease. Dig. Dis. Sci. 38: 1175-1182, 1993[Medline].

3.   Andersen, P., R. P. Adams, G. Sjøgaard, A. Thorboe, and B. Saltin. Dynamic knee extension as model for study of isolated exercising muscle in humans. J. Appl. Physiol. 59: 1647-1653, 1985[Abstract/Free Full Text].

4.   Bishop, J. M., K. W. Donald, S. H. Taylor, and P. N. Wormald. Changes in arterial-hepatic venous oxygen content difference during and after supine leg exercise. J. Physiol. (Lond.) 137: 309-317, 1957.

5.   Bradley, S. E. The hepatic circulation. In: Handbook of Physiology. Circulation. Bethesda, MD: Am. Physiol. Soc., 1963, sect. 2, vol. II, chapt. 41, p. 1387-1438.

6.   Bradley, S. E. Variations in hepatic blood flow in man during health and disease. N. Engl. J. Med. 240: 456-461, 1949[Medline].

7.   Bradley, S. E., F. J. Ingelfinger, G. P. Bradley, and J. J. Curry. The estimation of hepatic blood flow in man. J. Clin. Invest. 24: 890-897, 1945.

8.   Callum, K. G., J. I. Gaunt, M. L. Thomas, and N. L. Browse. Physiological studies in arteriomegaly. Cardiovasc. Res. 8: 373-383, 1974[Medline].

9.   Chauveau, M., B. Levy, J. F. Dessanges, E. Savin, O. Bailliart, and J. P. Martineaud. Quantitative Doppler blood flow measurement method and in vivo calibration. Cardiovasc. Res. 19: 700-706, 1985[Medline].

10.   Chien, S. Role of the sympathetic nervous system in hemorrhage. Physiol. Rev. 47: 214-288, 1967[Free Full Text].

11.   Christensen, N. J., and H. Galbo. Sympathetic nervous activity during exercise. Annu. Rev. Physiol. 45: 139-153, 1983[Medline].

12.   Clausen, J. P., K. Klausen, B. Rasmussen, and J. Trap-Jensen. Central and peripheral circulatory changes after training of the arms or legs. Am. J. Physiol. 225: 675-682, 1973.

13.   Delahunt, T. A., R. H. Geelkerken, J. Hermans, J. M. van Baalen, A. J. Vaughan, and J. H. van Bockel. Comparison of trans- and intra-abdominal duplex examinations of the splanchnic circulation. Ultrasound Med. Biol. 22: 165-171, 1996[Medline].

14.   Eriksen, M., B. A. Waaler, L. Walløe, and J. Wesche. Dynamics and dimensions of cardiac output changes in humans at the onset and at the end of moderate rhythmic exercise. J. Physiol. (Lond.) 426: 423-437, 1990[Abstract/Free Full Text].

15.   Fitzgerald, D. E., and A. M. O'Shaughnessy. Cardiac and peripheral arterial responses to isoprenaline challenge. Cardiovasc. Res. 18: 414-418, 1984[Medline].

16.   Flamm, S. D., J. Taki, R. Moore, S. F. Lewis, F. Keech, F. Maltais, M. Ahmad, R. Callahan, S. Dragotakes, N. Alpert, and H. W. Strauss. Redistribution of regional and organ blood volume and effect on cardiac function in relation to upright exercise intensity in healthy human subjects. Circulation 81: 1550-1559, 1990[Abstract/Free Full Text].

17.   Folse, R. Application of the sudden injection dye dilution principle to the study of the femoral circulation. Surg. Gynecol. Obstet. 120: 1194-1206, 1965[Medline].

18.   Gabriel, H., and W. Kindermann. Ultrasound of the abdomen in endurance athletes. Eur. J. Appl. Physiol. 73: 191-193, 1996.

19.   Ganz, V., A. Hlavová, A. Fronek, J. Linhart, and I. Prerovsky. Measurement of blood flow in the femoral artery in man at rest and during exercise by local thermodilution. Circulation 30: 86-89, 1964[Abstract/Free Full Text].

20.   Gill, R. W. Measurement of blood flow by ultrasound: accuracy and sources of error. Ultrasound Med. Biol. 11: 625-641, 1985[Medline].

21.   Gill, R. W. Pulsed Doppler with B-mode imaging for quantitative blood flow measurement. Ultrasound Med. Biol. 5: 223-235, 1979[Medline].

22.   Greenway, C. V., and R. D. Stark. Hepatic vascular bed. Physiol. Rev. 51: 23-65, 1971[Free Full Text].

23.   Grimby, G. Renal clearances during prolonged supine exercise at different loads. J. Appl. Physiol. 20: 1294-1298, 1965[Abstract/Free Full Text].

24.   Guldvog, I., M. Kjærnes, M. Thoresen, and L. Walløe. Blood flow in arteries determined transcutaneously by an ultrasonic doppler velocitymeter as compared to electromagnetic measurements on the exposed vessels. Acta Physiol. Scand. 109: 211-216, 1980[Medline].

25.   Haddy, F. J., and J. B. Scott. Metabolically linked vasoactive chemicals in local regulation of blood flow. Physiol. Rev. 48: 688-707, 1968[Free Full Text].

26.   Hollenberg, N. K. The renal circulation. In: The Peripheral Circulation, edited by R. Zelis. New York: Grune & Stratton, 1975, p. 131-150.

27.  Hopman, M. T. E., X. H. Eijsbouts, G. M. de Wild, and W. N. J. C. van Asten. Leg blood flow and oxygen uptake in elderly compared to young individuals during incremental exercise (Abstract). Specialty Conference on American College of Sports Medicine. Regulation of Oxidative Metabolism and Blood Flow in Skeletal Muscle: Physiological, Biophysical, Biochemical, and Molecular Aspects, 28-30 Sept. 1995, Indianapolis, IN.

28.  Hultman, E. Blood circulation in the liver under physiological and pathological conditions. Scand. J. Clin. Lab. Invest. 18, Suppl. 92: 27-41, 1966.

29.   Hussain, S. T., R. E. Smith, R. F. M. Wood, and M. Bland. Observer variability in volumetric blood flow measurements in leg arteries using duplex ultrasound. Ultrasound Med. Biol. 22: 287-291, 1996[Medline].

30.   Isnard, R., P. Lechat, H. Kalotka, H. Chikr, S. Fitoussi, J. Salloum, J.-L. Golmard, D. Thomas, and M. Komajda. Muscular blood flow response to submaximal leg exercise in normal subjects and in patients with heart failure. J. Appl. Physiol. 81: 2571-2579, 1996[Abstract/Free Full Text].

31.   Iwao, T., A. Toyonaga, M. Ikegami, M. Sumino, K. Oho, M. Sakaki, H. Shigemori, K. Tanikawa, and J. Iwao. Effects of exercise-induced sympathoadrenergic activation on portal blood flow. Dig. Dis. Sci. 40: 48-51, 1995[Medline].

32.   Jäger, K., A. Bollinger, C. Valli, and R. Ammann. Measurement of mesenteric blood flow by duplex scanning. J. Vasc. Surg. 3: 462-469, 1986[Medline].

33.   Katz, L. N., and S. Rodbard. The integration of the vasomotor responses in the liver with those in other systemic vessels. J. Pharmacol. Exp. Ther. 67: 407-422, 1939[Abstract/Free Full Text].

34.  Korner, P. I., J. P. Chalmers, and S. W. White. Some mechanisms of reflex control of the circulation by the sympatho-adrenal system. Circ. Res. 20, 21; Suppl. 3: 157-172, 1967.

35.   Levy, B. I., W. R. Valladares, A. Ghaem, and J. P. Martineaud. Comparison of plethysmographic methods with pulsed Doppler blood flowmetry. Am. J. Physiol. 236 (Heart Circ. Physiol. 5): H899-H903, 1979.

36.   Lewis, P., J. V. Psaila, R. H. Morgan, W. T. Davies, and J. P. Woodcock. Common femoral artery volume flow in peripheral vascular disease. Br. J. Surg. 77: 183-187, 1990[Medline].

37.   Mellander, S., and B. Johansson. Control of resistance, exchange and capacitance functions in the peripheral circulation. Pharmacol. Rev. 20: 117-196, 1968[Free Full Text].

38.   Mittelstadt, S. W., L. B. Bell, K. P. O'hagan, J. E. Sulentic, and P. S. Clifford. Muscle chemoreflex causes renal vascular constriction. Am. J. Physiol. 270 (Heart Circ. Physiol. 39): H951-H956, 1996[Abstract/Free Full Text].

39.   Nakamura, T., F. Moriyasu, N. Ban, O. Nishida, T. Tamada, T. Kawasaki, M. Sakai, and H. Uchino. Quantitative measurement of abdominal arterial blood flow using image-directed Doppler ultrasonography: superior mesenteric, splenic, and common hepatic arterial blood flow in normal adults. J. Clin. Ultrasound 17: 261-268, 1989[Medline].

40.   Nimura, Y., K. Miyatake, N. Kinoshita, M. Okamoto, S. Kawamura, S. Beppu, and H. Sakakibara. New approach to noninvasive assessment of blood flow in the major arteries in the abdomen by two-dimensional Doppler echography. In: Ultrasound 82. Proceedings of 3rd Meeting of the World Federation for Ultrasound in Medicine and Biology, 5th World Congress of Ultrasound in Medicine and Biology, 26-30 July 1982, Brighton, England, edited by R. A. Lerski, and P. Morley. Oxford: Pergamon, 1983, p. 447-451.

41.   Plotnick, G. D., M. C. Corretti, and R. A. Vogel. Effect of antioxidant vitamins on the transient impairment of endothelium-dependent brachial artery vasoactivity following a single high-fat meal. JAMA 278: 1682-1686, 1997[Abstract].

42.   Qamar, M. I., and A. E. Read. Effects of exercise on mesenteric blood flow in man. Gut 28: 583-587, 1987[Abstract/Free Full Text].

43.   Rådegran, G. Ultrasound Doppler estimates of femoral artery blood flow during dynamic knee extensor exercise in humans. J. Appl. Physiol. 83: 1383-1388, 1997[Abstract/Free Full Text].

44.   Reagan, T. R., C. W. Miller, and D. E. Strandness, Jr. Transcutaneous measurement of femoral artery flow. J. Surg. Res. 11: 477-482, 1971[Medline].

45.   Richardson, R. S., D. C. Poole, D. R. Knight, S. S. Kurdak, M. C. Hogan, B. Grassi, E. C. Johnson, K. F. Kendrick, B. K. Erickson, and P. D. Wagner. High muscle blood flow in man: is maximal O2 extraction compromised? J. Appl. Physiol. 75: 1911-1916, 1993[Abstract/Free Full Text].

46.   Rowell, L. B. Human cardiovascular adjustments to exercise and thermal stress. Physiol. Rev. 54: 75-159, 1974[Free Full Text].

47.   Rowell, L. B. Measurement of hepatic-splanchnic blood flow in man by dye techniques. In: Dye Curves: The Theory and Practice of Indicator Dilution, edited by D. A. Bloomfield. Baltimore, MD: University Park, 1974, p. 209-229.

48.   Rowell, L. B. Regulation of splanchnic blood flow in man. Physiologist 16: 127-142, 1973[Medline].

49.   Rowell, L. B., J. R. Blackmon, and R. A. Bruce. Indocyanine green clearance and estimated hepatic blood flow during mild to maximal exercise in upright man. J. Clin. Invest. 43: 1677-1690, 1964.

50.   Rowell, L. B., J. R. Blackmon, R. H. Martin, J. A. Mazzarella, and R. A. Bruce. Hepatic clearance of indocyanine green in man under thermal and exercise stresses. J. Appl. Physiol. 20: 384-394, 1965[Abstract/Free Full Text].

51.   Rowell, L. B., G. L. Brengelmann, J. R. Blackmon, and J. A. Murray. Redistribution of blood flow during sustained high skin temperature in resting man. J. Appl. Physiol. 28: 415-420, 1970[Free Full Text].

52.   Rowell, L. B., G. L. Brengelmann, J. R. Blackmon, R. D. Twiss, and F. Kusumi. Splanchnic blood flow and metabolism in heat-stressed man. J. Appl. Physiol. 24: 475-484, 1968[Free Full Text].

53.   Rowell, L. B., J.-M. R. Detry, J. R. Blackmon, and C. Wyss. Importance of the splanchnic vascular bed in human blood pressure regulation. J. Appl. Physiol. 32: 213-220, 1972[Free Full Text].

54.   Rowell, L. B., E. J. Masoro, and M. J. Spencer. Splanchnic metabolism in exercising man. J. Appl. Physiol. 20: 1032-1037, 1965[Abstract/Free Full Text].

55.   Rowell, L. B., and D. S. O'Leary. Reflex control of the circulation during exercise: chemoreflexes and mechanoreflexes. J. Appl. Physiol. 69: 407-418, 1990[Abstract/Free Full Text].

56.   Saltin, B. Hemodynamic adaptations to exercise. Am. J. Cardiol. 55: 42D-47D, 1985[Medline].

57.   Shoemaker, J. K., M. J. MacDonald, and R. L. Hughson. Time course of brachial artery diameter responses to rhythmic handgrip exercise in humans. Cardiovasc. Res. 35: 125-131, 1997[Abstract/Free Full Text].

58.   Shoemaker, J. K., Z. I. Pozeg, and R. L. Hughson. Forearm blood flow by Doppler ultrasound during rest and exercise: tests of day-to-day repeatability. Med. Sci. Sports Exerc. 28: 1144-1149, 1996[Medline].

59.   Strandell, T., and J. T. Shepherd. The effect in humans of increased sympathetic activity on the blood flow to active muscles. Acta Med. Scand. Suppl. 472: 146-167, 1967[Medline].

60.   Taylor, K. J. W., P. N. Burns, J. P. Woodcock, and P. N. T. Wells. Blood flow in deep abdominal and pelvic vessels: ultrasonic pulsed-Doppler analysis. Radiology 154: 487-493, 1985[Abstract/Free Full Text].

61.   Tschakovsky, M. E., J. K. Shoemaker, and R. L. Hughson. Beat-by-beat forearm blood flow with Doppler ultrasound and strain-gauge plethysmography. J. Appl. Physiol. 79: 713-719, 1995[Abstract/Free Full Text].

62.   Vänttinen, E. Electromagnetic measurement of the arterial blood flow in the