AJP - Heart Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 292: H215-H223, 2007. First published August 25, 2006; doi:10.1152/ajpheart.00681.2006
0363-6135/07 $8.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
292/1/H215    most recent
00681.2006v1
Right arrow Alert me when this article is cited
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 Web of Science
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 Web of Science (5)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stewart, J. M.
Right arrow Articles by Medow, M. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stewart, J. M.
Right arrow Articles by Medow, M. S.

Changes in regional blood volume and blood flow during static handgrip

Julian M. Stewart,1,2 Leslie D. Montgomery,1,3 June L. Glover,1 and Marvin S. Medow1,2

Department of 1Pediatrics and 2Physiology, New York Medical College, Valhalla, New York; and 3LDM Associates, San Jose, California

Submitted 27 June 2006 ; accepted in final form 17 August 2006


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Increased blood pressure (BP) and heart rate during exercise characterizes the exercise pressor reflex. When evoked by static handgrip, mechanoreceptors and metaboreceptors produce regional changes in blood volume and blood flow, which are incompletely characterized in humans. We studied 16 healthy subjects aged 20–27 yr using segmental impedance plethysmography validated against dye dilution and venous occlusion plethysmography to noninvasively measure changes in regional blood volumes and blood flows. Static handgrip while in supine position was performed for 2 min without postexercise ischemia. Measurements of heart rate and BP variability and coherence analyses were used to examine baroreflex-mediated autonomic effects. During handgrip exercise, systolic BP increased from 120 ± 10 to 148 ± 14 mmHg, whereas heart rate increased from 60 ± 8 to 82 ± 12 beats/min. Heart rate variability decreased, whereas BP variability increased, and transfer function amplitude was reduced from 18 ± 2 to 8 ± 2 ms/mmHg at low frequencies of ~0.1 Hz. This was associated with marked reduction of coherence between BP and heart rate (from 0.76 ± 0.10 to 0.26 ± 0.05) indicative of uncoupling of heart rate regulation by the baroreflex. Cardiac output increased by ~18% with a 4.5% increase in central blood volume and an 8.5% increase in total peripheral resistance, suggesting increased cardiac preload and contractility. Splanchnic blood volume decreased reciprocally with smaller decreases in pelvic and leg volumes, increased splanchnic, pelvic and calf peripheral resistance, and evidence for splanchnic venoconstriction. We conclude that the exercise pressor reflex is associated with reduced baroreflex cardiovagal regulation and driven by increased cardiac output related to enhanced preload, cardiac contractility, and splanchnic blood mobilization.

exercise pressor reflex; mechanoreflex; metaboreflex

STATIC VOLUNTARY isometric contraction evokes both central command (9), which is independent of afferents arising from exercising muscle, and the exercise pressor reflex, which is strictly dependent on sensory afferents from exercising muscle (29). The exercise pressor reflex results in vagal withdrawal (14) and sympathetic activation (26), which together increases heart rate (HR) and blood pressure during exercise. The pressor reflex is composed of two parts comprising the muscle mechanoreflex (22) and the muscle metaboreflex, which is evoked as muscle blood flow fails to keep up with metabolic demands (6, 21, 29). Since Alam and Smirk's landmark work (1) the most marked pressor responses are believed to develop during the phase of muscle ischemia and depend on the amount of muscle involved (10), on age (31), on gender (30), and on the magnitude of muscle tension (42) produced by the activation of group III and IV muscle afferents (22, 23).

Effects of the exercise pressor reflex on regional hemodynamics are only partially understood. Thus in experiments on conscious dogs, O'Leary's laboratory (45) studied a graded metaboreflex and demonstrated increased cardiac output in part due to increased sympathetic stimulation of the heart (36) and in part due to increased central blood volume estimated by increased right atrial pressure and implying increased ventricular preload. Increased stroke volume has also been demonstrated in humans during rhythmic handgrip followed by postfatigue ischemic occlusion (7). In the canine model, total peripheral resistance remains relatively unchanged during mild to moderate exercise (2) even though skeletal muscle resistance is increased (35) and there is marked renovascular constriction (2). Marked increases of renovascular resistance have also been observed in humans and primarily attributed to the mechanoreflex component of the pressor reflex (32, 46).

The observed increase in cardiac output requires increased venous return. It remains unclear precisely how this occurs. The purpose of the present work therefore was to explore the hypothesis that the splanchnic vasculature is the major source of centrally redistributed blood during the exercise pressor reflex and that redistribution occurs as a result of pressor reflex-induced splanchnic arterial vasoconstriction and venoconstriction. These studies are unique in that they employ impedance plethysmography to measure changes in regional blood volumes related to the stimulation resulting from static pressor reflex activation.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Subjects and Experimental Outline

To test this hypothesis we studied 16 healthy volunteer subjects aged 20–27 yr (median = 24.5 yr, 7 male, 9 female). Average weight (±SD) was 70 ± 14 kg, average height was 169 ± 10 cm, average body mass index was 24 ± 4 kg/m2. Patients were normotensive. All measurements were made supine. Resting supine systolic blood pressure was 118 ± 10 mmHg, resting supine diastolic blood pressure was 63 ± 8 mmHg, and resting heart rate was 59 ± 9 beats/min.

All subjects were free from systemic illnesses. Subjects were not taking medications and were nonsmokers. All subjects had no evidence of cardiovascular or systemic illness. There were no competitive athletes or bedridden subjects. Informed consent was obtained. All protocols were approved by the Committee for the Protection of Human Subjects (IRB) of New York Medical College.

Laboratory Evaluation

We monitored blood pressure and heart rate continuously and estimated changes in thoracic, splanchnic, pelvic, and calf segmental blood volumes and blood flows by impedance plethysmography while the subjects were supine and throughout static handgrip as explained below. All subjects had blood volume and resting cardiac output measured by indocyanine green (ICG) dye dilution methods, and results were compared between impedance measurements and venous occlusion plethysmography, green dye cardiac output, and dye estimates of splanchnic blood flow (see Dye dilution measurement of blood volume and cardiac output).

Protocol

Tests began at least 2 h after a light breakfast. An intravenous catheter was placed in the right antecubital fossa. After a 30-min acclimatization period, we used supine impedance plethysmography (IPG) to continuously measure resistance (R0) and beat-to-beat change in resistance ({Delta}R) of thoracic, splanchnic, pelvic, and leg segments (terms defined below) while we simultaneously estimated supine cardiac output, blood volume, and effective portal vein blood flow by the ICG dye dilution technique. Next, calf blood flow was measured by strain-gauge plethysmography (SPG). We verified respective correlations of impedance measurements of thoracic blood flow, calf blood flow, and splanchnic blood flow with dye dilution cardiac output, SPG calf blood flow, and the exponential decay coefficient of the concentration of ICG, which approximates portal blood flow divided by blood volume within a constant representing hepatic dye extraction (see Dye dilution measurement of blood volume and cardiac output). We also compared impedance methods with reference methods for measuring blood flow using Bland-Altman Plots (3). These results appear in Fig. 1. On this basis we used impedance measurements to continuously estimate changes in segmental blood flows throughout the handgrip evaluation.


Figure 1
View larger version (19K):
[in this window]
[in a new window]

  		Fig. 1. Top left: estimated cardiac index (CI) calculated using indocyanine green (ICG) dye dilution technique on the abscissa compared with CI calculated using impedance methods; top right: corresponding Bland-Altman plot. Middle left: estimated splanchnic blood using ICG dye dilution technique (ordinate) compared with splanchnic blood flow using impedance plethysmography (abscissa); middle right: corresponding Bland-Altman plot. Bottom left: calf blood flow measured by venous occlusion plethysmography (ordinate) and estimated by IPG (abscissa); bottom right: corresponding Bland-Altman plot. Correlation coefficients are shown. There are small fixed errors in thoracic blood flow, as well as fixed and proportional biases in splanchnic and calf blood flows, but no nonuniformities of error.

 
Early in the experiment, each subject performed two brief maximal voluntary contractions (MVCs) with their left hand using a handgrip dynamometer (Lafayette Instruments, Lafayette, IN). Subsequently, subjects performed static handgrip while impedance, heart rate, and blood pressure monitoring continued. Handgrip was preceded by a baseline phase lasting 5 min, during which impedance, heart rate, and blood pressure data were collected. Subjects then performed 120 s of sustained isometric handgrip at 35% MVC. This was typically exhaustive exercise. Posthandgrip circulatory arrest was not performed because we were interested in the exercise pressor reflex rather than measurements made after exercise. A feedback system allowed subjects to maintain force near constant. Blood pressure, electrocardiogram, and IPG flow and volume measurements were made continuously but are reported at baseline, 1 min, and 2 min of sustained handgrip and during a recovery period.

Details of Method

Heart rate and blood pressure monitoring. A single electrocardiogram lead was recorded for rhythm. Upper extremity blood pressure was continuously monitored with a finger arterial plethysmograph (Finometer, FMS, Amsterdam, The Netherlands) placed on the right middle or index finger. Electrocardiogram and Finometer pressure data were interfaced to a personal computer through an analog-to-digital converter (DI-720 DataQ Ind, Milwaukee, WI). Heart rate was derived from arterial pressure data. Finometer data were calibrated to a brachial artery oscillographic pressure. All data were multiplexed with strain gauge and impedance data and were thereby synchronized. Continuous blood pressure data were used to identify pulses and to compute heart rate and blood pressure variability indexes and to perform and compare coherence analyses among the subject groups.

Heart rate and blood pressure variability, coherence analysis. To investigate the effects of handgrip on the cardiovagal baroreflex regulation of heart rate, we measured indexes of heart rate and blood pressure variability. There is evidence for important effects of both the mechanoreflex and the metaboreflex components of the exercise pressor reflex on baroreflex function (18, 24, 54). The transfer function between blood pressure and heart rate at middle frequency (~0.1 Hz) relates to sympathetic modulation of blood pressure transduced to heart rate changes primarily by way of vagal efferents of the baroreflex (28). We examined coherence and transfer function phase and amplitude (baroreflex gain) during handgrip: baseline heart rate and blood pressure data were captured during the 5-min resting period. Beats were acquired for the first minute and second minute of handgrip. Data were analyzed for each minute separately and for both minutes combined as a single beat sequence. Data were also collected for a 1-min period during recovery from handgrip centered on the time of minimum blood pressure for comparison. We used custom software to collect digital sequences containing RR interval and systolic, diastolic, and mean blood pressures for each heartbeat, as previously described (47). The coherence function was also calculated at low frequencies. Usually a coherence of at least 0.5 is used to indicate a significant baroreceptor-mediated relationship between changes in blood pressure and changes in heart rate (38). Coherence less than 0.5 suggests an "uncoupling" of the baroreflex modulation of heart rate by blood pressure (28).

Dye dilution measurement of blood volume and cardiac output. We used ICG dye dilution technique to measure blood volume and cardiac output (4) and to estimate splanchnic blood flow in terms of portal uptake of the dye (44). We used a spectrophotometric photosensor (DDG2000, Nihon-Kohden) previously validated in clinical studies (16, 19). The dye decay curve fits a monoexponential V0 exp – [Kt], where K represents clearance by the liver divided by blood volume and clearance = (1 – hematocrit) x Q x E (44).

We defined effective portal blood flow = Q x E = (K x BV)/(1 – hematocrit), where BV is blood volume, Q is portal blood flow, and E is the hepatic dye extraction ratio.

We measured the hematocrit from antecubital venous blood, and extrapolated the dye decay curve to the time of dye injection (t = 0) yielding estimated blood volume. A semilogarithmic fit to the exponential decay yields the parameter K, which was used to estimate portal blood flow and thus splanchnic blood flow within a constant. Echo-Doppler measurements of portal venous blood flow and ICG clearance methods compare favorably (5).

Calf blood flow by SPG. We used venous occlusion strain-gauge plethysmography in all subjects to measure calf blood flow. Supine measurements were made at the beginning of experiments, and measurements were compared with impedance estimates of blood flow. We have previously employed these techniques (48, 50).

Impedance plethysmography to measure changes in segmental blood volumes and blood flows. Impedance plethysmography (IPG) has been used to detect internal volume shifts during orthostatic stress (8, 11, 33, 53). IPG is routinely used to measure changes in cardiac output in the form of impedance cardiography (8, 11). We have used this technique extensively before with repeatable and physiologically reasonable outcomes (49, 51). Our device employs a Tetrapolar High Resolution Impedance Monitor (THRIM) four-channel digital impedance plethysmograph (UFI) applied to four anatomic segments defined in practice by electrode placement. These are designated the thoracic segment (supraclavicular area to xyphoid process), the splanchnic segment (xyphoid process to iliac crest), the pelvic segment incorporating lower pelvis to the knee (iliac crest to knee), and the leg or calf segment (upper calf just below the knee to the ankle) (49, 51). Ag/AgCl electrocardiogram electrodes were attached at these segmental boundaries and also to the right foot and right hand, where they served as current injectors. The IPG uses a 50-kHz, 0.1 mA RMS constant current signal between the foot and hand electrodes. Electrical resistance values were measured using the segmental pairs as sampling electrodes. The midline distance between the sampling electrodes (L) was measured with a tape measure. We also measured the circumferences of calf, thigh, hips, waist, and chest to obtain approximate volume contents of each anatomic segment. We estimated the change in blood volume in each segment during handgrip from the formula:

Formula
where {rho} is electrical conductivity of blood estimated as 53.2 x exp(hematocrit x 0.022) given by Geddes and Sadler (12). R0 is the resistance of a specific segment before handgrip, R1 is the resistance during handgrip, and {Delta}R is the change in resistance (R1 – R0) in a specific segment during handgrip. {rho} was regarded as constant during the maneuver.

IPG was also used to measure segmental blood flows (33). Transient blood flows have been similarly quantitated during orthostasis (49) and during the Valsalva maneuver (51). Pulsatile changes in electrical resistance for each segment were employed to compute the time derivative {partial}R/{partial}t, which we used to obtain the blood flow responses of each body segment during handgrip.

Blood flow was estimated for an entire anatomic segment from the formula:

Formula
where HR is heart rate, T is the ejection period, R is the pulsatile resistance, and R0 is the baseline resistance at a given angle of tilt. Respiratory artifact was removed from the signal using a custom, Fourier-based frequency selection technique. IPG flows are expressed in milliliters per minute for anatomic segment and can be normalized by dividing by estimated segmental volume.

Statistics

All tabular and text results are reported as means ± SD. Graphics are presented as means ± SE. Changes in heart rate and blood pressure variability and in impedance estimates of regional blood flow and regional blood volume, heart rate, and mean and systolic blood pressures were compared by analysis of variance for repeated measures at baseline before handgrip, 1 min after the start of handgrip, 2 min after the start of handgrip, and during recovery using the minimum of blood pressure during recovery as the time of comparison. Results were calculated using SPSS (Statistical Package for the Social Sciences) software version 11.0.


   RESULTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
All subjects completed the protocol successfully. Blood volume for each subject was normal, and the mean was 5.2 ± 1.5 liter (73 ± 12 ml/kg) and the mean hematocrit was 41 ± 3%. Data were similar for males and females and pooled gender data are presented.

Heart Rate and Blood Pressure During Handgrip

Heart rate and blood pressure are shown in Fig. 2. Data from a representative subject shows the approximately linear increase in blood pressure as a function of time during handgrip. This linearity was observed in all subjects. Heart rate increased rapidly during the early course of static handgrip and more slowly thereafter. Percent changes in heart rate and blood pressure are based on paired data assessments and are also shown in Fig. 2. Absolute blood pressures (systolic and mean) and heart rates at stages of handgrip are shown in Table 1. On average systolic and mean arterial blood pressure increased significantly from baseline at 1 min of handgrip (P < 0.0001) and increased further at 2 min of handgrip (P < 0.0001) returning at recovery to a pressure that was slightly lower than baseline (P < 0.001). Heart rate increased significantly from baseline at 1 min (P < 0.0005) and further at 2 min (P < 0.005), returning at recovery to a heart rate that was similar to baseline.


Figure 2
View larger version (19K):
[in this window]
[in a new window]

  		Fig. 2. Left: representative heart rate (HR, top) and blood pressure (BP, bottom) from an actual subject during static handgrip. Right: changes in HR and mean arterial blood pressure (MAP) averaged over all subjects. Measurements are shown for 1 and 2 min after the onset of handgrip as well as during the recovery phase. *P < 0.05 compared with baseline.

 

View this table:
[in this window]
[in a new window]

  		Table 1. Heart rate and blood pressure data

 
Heart Rate and Blood Pressure Variability, Coherence Analysis

Decreased HRV during handgrip varied BPV. Data are shown in Table 1. Total heart rate variability (HRV) was significantly decreased compared with baseline (P < 0.001) at 1 and 2 min of handgrip and returned to baseline values during recovery. Low-frequency HRV power decreased (P < 0.01) during the first minute of handgrip but then was similar to baseline during the second minute of handgrip. High-frequency HRV power was decreased during both 1 and 2 min of handgrip but was similar to baseline during recovery. The ratio of low-frequency to high-frequency power (LF/HF) was increased during the second minute of handgrip compared with baseline (P < 0.001). Blood pressure variability (BPV) was decreased in the first minute of handgrip (P < 0.01) and was increased during the second minute (P < 0.05) compared with baseline.

Lack of significant low-frequency HRV-BPV coherence during handgrip. Although transfer function gain (transfer magnitude) was markedly reduced (P < 0.001) throughout handgrip and recovery, this was associated with a reduction of coherence (P < 0.001) well below the 0.5-cutoff for significant coherence. Thus changes in transfer magnitude (i.e., baroreflex gain) may not be strictly interpretable under these circumstances. The data suggest an uncoupling of baroreflex mediation of heart rate and blood pressure during handgrip.

Impedance Plethysmographic Changes in Segmental Blood Volumes and Blood Flows

Reciprocal thoracic (central)–splanchnic blood volume changes during handgrip. Representative changes in segmental impedance and in the percent change in blood volume during handgrip are shown in Fig. 3. There are opposite changes within the thoracic and splanchnic segments. Significant increases in impedance also occur within pelvic and calf segments but are of much smaller magnitude than splanchnic increments.


Figure 3
View larger version (21K):
[in this window]
[in a new window]

  		Fig. 3. Splanchnic (dot-dash line) and thoracic (solid line) graphs are shown for measured impedance (top) and corresponding calculated percent change in segmental blood volume (bottom). Changes are reciprocal with increased impedance in the splanchnic segment and decreased impedance in the thoracic segment during handgrip. End, cessation of the hangrip.

 
Central blood volume increases and peripheral volume decreases during handgrip. Percent changes in all segmental blood volumes are shown in Fig. 4. There is an increase in thoracic volume noted during the first minute of handgrip, which reaches significance (P < 0.025) during the second minute. Splanchnic volume changes in reciprocal fashion with smaller changes noted in pelvic and calf volumes, which both decreased significantly (P < 0.05) during the second minute of handgrip. Comparable changes in the percent volume of the calf diameter were measured by SPG.


Figure 4
View larger version (10K):
[in this window]
[in a new window]

  		Fig. 4. Percent changes from baseline in thoracic, splanchnic, pelvic, and calf blood volumes during handgrip averaged over all subjects at 1 and 2 min after starting handgrip and during recovery. The largest percent changes (increases) occur in the thoracic (central) blood segment with smaller reciprocal decreases in splanchnic segment. Changes in the pelvic and calf segments are smaller than measured in the thoracic and splanchnic regions. *P < 0.05 compared with baseline.

 
Segmental blood flow changes during handgrip: stable splanchnic blood flow suggests venoconstriction. Changes in segmental blood flow are shown in Fig. 5. Cardiac output is increased by nearly 20% (P < 0.01) throughout handgrip, whereas splanchnic blood flow tends to be unchanged during handgrip, and pelvic and calf blood flows are increased at 2 min (P < 0.025). Stable splanchnic blood flow with decreasing splanchnic volume may indicate active splanchnic venoconstriction (see DISCUSSION).


Figure 5
View larger version (14K):
[in this window]
[in a new window]

  		Fig. 5. Percent changes in segmental blood flow. From top to bottom: changes in thoracic, splanchnic, pelvic, and leg (calf). Blood flow increases for the central thoracic, pelvic, and calf segments but is relatively unchanged for the splanchnic segment. *P < 0.05 compared with baseline.

 
Segmental arterial resistance increases during handgrip-modest increase in total peripheral resistance. We calculated segmental vascular resistance using the formula R = mean arterial pressure/segmental blood flow. Percent changes in vascular resistance are shown in Fig. 6. Total peripheral resistance is modestly increased (P < 0.025) during the second minute of handgrip but returns to baseline during recovery. Similar increases in splanchnic, pelvic and calf resistances were noted.


Figure 6
View larger version (11K):
[in this window]
[in a new window]

  		Fig. 6. Percent changes in segmental arterial resistance. From top to bottom: changes in thoracic, splanchnic, pelvic, and leg (calf). Total peripheral resistance (TPR, thoracic resistance) was increased by the second minute of handgrip and was increased in splanchnic, pelvic and calf segments during the entire handgrip period. All resistances returned to baseline during recovery. *P < 0.05 compared with baseline.

 

   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
Main Findings

Regional blood volume redistribution and hemodynamics during handgrip. Our results demonstrate an integrated approach by which changes in hemodynamically important regional circulations contribute to the redistribution of blood volume and blood flow during static handgrip. The most significant new finding is that the increase in central blood volume and cardiac output evoked by the exercise pressor reflex is produced in large part by emptying of the splanchnic vascular bed through splanchnic venoconstriction and arterial vasoconstriction. We observed a 4.5% increase in central blood volume associated with a 2.5% decrease in splanchnic volume. Since the splanchnic vascular bed receives ~25% of the cardiac output and contains ~30% of the blood volume, it is reasonable that the splanchnic vasculature is able to rapidly transfer its blood to the central circulation (41). Relatively smaller but directionally similar decreases in segmental blood volume occur within the pelvic and calf segments. The finding of splanchnic emptying at relatively constant splanchnic blood flow implies the active contribution of venoconstriction. In addition, there is an increase in total peripheral resistance and therefore cardiac afterload. The magnitude of the increase in cardiac output, the increase in central blood volume, and the increase in end-systolic pressure suggest that there is also an increase in cardiac contractility.

Baroreflex regulation of heart rate during handgrip (cardiovagal regulation). Cardiovagal baroreflex regulation is calculated in the present work. This technique mainly estimates parasympathetic control of heart rate. If usual coherence criteria are employed, our data also imply that parasympathetic baroreflex regulation of heart rate may become relatively less important during handgrip. Note that the data do not inform on baroreflex effects on peripheral resistance or on cardiac contractility (28).

Comparisons with the Literature

Heart rate and blood pressure during handgrip. Our observations are consistent with the literature showing changes in both blood pressure and heart rate during and after release of hand grip. The time course and magnitude of increases in heart rate and blood pressure are similar to data observed elsewhere in healthy human subjects (1, 6, 10, 21).

Variability analyses. Our measurements of heart rate variability are consistent with past data of Kluess et al. (25) and with the extended analyses of Iellamo et al. (18) in showing a relative increase in low-frequency to high-frequency spectral components and a reduction in baroreflex gain. We would, however, interpret such data differently in light of the progressive decrease in coherence between heart rate and blood pressure, which falls well below the 0.5 threshold for significance of coherence (Table 1) and is synchronous with the reduction in baroreflex gain. This can be interpreted as resulting from an uncoupling of heart rate from blood pressure modulation of the baroreflex during the isometric static exercise pressor reflex.

Segmental hemodynamics. These data, showing segmental changes in blood volume during hand grip measured by impedance plethysmography, are new in humans and are consistent with other findings in both human and animal literature. They are also unique because these measurements are noninvasive. Thus, for example, O'Leary's laboratory (45) have demonstrated the increase in central blood volume and ventricular performance (37) with consequent increased cardiac output (2), which occurs during the metaboreflex. This is in agreement with our measurements and with the observations on heart rate and stroke volume of Crisafulli et al. (7) during rhythmic handgrip contraction followed by local ischemic occlusion.

Increases in total peripheral resistance have also been shown in humans (17, 27) but not in normal dogs (2) during submaximal exercise. Thus in humans the increase in blood pressure during the pressor reflex has often been ascribed to vasoconstriction alone. This species difference in vasoconstriction may represent a more situational than qualitative difference: thus pronounced vasoconstriction does occur by metaboreflex if cardiac output is held constant by ventricular pacing + beta-block (45), during maximal exercise wherein cardiac output cannot increase further (2), during heart failure (15), or in normal dogs after arterial baroreceptor denervation (24).

Whereas a modest increase in total peripheral resistance was observed during our studies, it was combined with a proportionately greater increase in cardiac output related at least in part to an increase in central volume. Whereas an accurate calculation of ventricular elastance was not feasible using current data, the results suggest an increase in cardiac contractility as observed in dogs by Sala-Mercado and coworkers (43).

In addition, we found that arterial resistance increased in splanchnic, pelvic, and calf segments to a similar degree, although blood flow did not change in the splanchnic segment and actually increased in the pelvic and calf segments due to the increase in blood pressure. Similar observations concerning splanchnic resistance have been made by Waaler and associates (52). Since neither blood flow changes nor blood volume shifts were reported, it was not possible to draw conclusions concerning regional blood volume changes from their data. However, the lack of change in splanchnic blood flow with decreasing splanchnic segmental blood volume in our data may support the hypothesis of venoconstriction. Active venoconstriction is confirmed if there is a decrease in venous volume while venous pressure is kept constant. This may also be true if there is perfusion at constant flow provided there is no reduction in central venous pressure (40). Canine data suggest that there is actually an increase in right atrial pressure during ischemic exercise (45), which should result in an increase in central venous pressure. Taken together the data and literature support the proposal of active splanchnic venoconstriction during static handgrip in humans.

Limitations

Impedance plethysmography is an indirect measurement of blood flow, and the accuracy and validity of its use for such measurements may be questioned. We tried to resolve this issue by comparing impedance measurements to standard reference methods such as ICG dye dilution (for cardiac output and for portal venous blood flow) and venous occlusion plethysmography (for calf blood flow). Comparisons show reasonable albeit imperfect correlations between reference standard and impedance measurements. There are both fixed and proportional biases but no nonuniformities of error. Thus, within limits, and for purposes of continuous monitoring, we believe invasive testing can be replaced by noninvasive testing. However, whereas the ICG method can yield accurate cardiac outputs, neither this reference standard method (as implemented in the current study) nor impedance methods are capable of giving true splanchnic flow results. Thus with ICG dye we calculated dye clearance rather than portal or hepatic blood flow, whereas impedance methods are best suited for detecting relative or percent changes in blood volume. Invasive measures to obtain hepatic extraction ratios in each subject are beyond the scope of current studies and would need repeated reassessments throughout static handgrip.

ICG estimates of portal blood flow were hampered by the lack of computation of the hepatic dye extraction ratio. As explained in MATERIALS AND METHODS, there is an implicit assumption of equal extraction in all patients with an extraction ratio of 1.0. Similar extraction ratios seem to be a reasonable assumption among healthy subjects.

Heart rate and blood pressure variability indexes are not reference standards for autonomic or baroreflex measurements. However, measured indexes have been consistent with invasive forms of measurement such as microneurography. (39)

Our aim was to assess the hemodynamic responses induced by exercise pressure reflex during exercise. Other confounding factors, such as central command, humoral changes, physical factors, and other blood-borne biochemical factors may be present during exercise. This leads many investigators to perform measures immediately after peak exercise during peripheral circulatory occlusion ischemia, which was not done here. However, central command, whereas responsible for much of the increase in heart rate and respirations during exercise, does not appear to increase sympathetic outflow unless the intensity of the exercise is near maximal (20), and humoral contributions appear to require a more sustained form of exercise to achieve importance (34). Nevertheless, central command, in particular may contribute to measured changes in heart rate.


   GRANTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This study was supported by National Heart, Lung, and Blood Institute Grants 1RO1HL-66007 and 1R01HL-074873.


   ACKNOWLEDGMENTS
 
We thank members of the Department of Pediatrics, especially its Chairman, Dr. Leonard Newman, and the Division of Pediatric Cardiology, especially its Director, Michael H. Gewitz, for unflagging support. We also acknowledge our intellectual debt to our mentors, Dr. Thomas H. Hintze, Dr. Gabor Kaley, Dr. David Robertson, and Dr. Phillip Low for constant inspiration and stimulation.


   FOOTNOTES
 

Address for reprint requests and other correspondence: J. M. Stewart, Professor of Pediatrics and Physiology, Research Division and Hypotension Laboratory, New York Medical College, Suite 3050, 19 Bradhurst Ave., Hawthorne, NY 10532 (e-mail: stewart{at}nymc.edu)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 

  1. Alam M, Smirk FH. Observations in man upon a blood pressure raising reflex arising from the voluntary muscles. J Physiol 89: 372–383, 1937.
  2. Augustyniak RA, Collins HL, Ansorge EJ, Rossi NF, O'Leary DS. Severe exercise alters the strength and mechanisms of the muscle metaboreflex. Am J Physiol Heart Circ Physiol 280: H1645–H1652, 2001.[Abstract/Free Full Text]
  3. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1: 307–310, 1986.[CrossRef][Web of Science][Medline]
  4. Bloomfield DA. Dye Curves: The Theory and Practice of Indicator Dye Dilution. Baltimore, MD: University Park Press, 1974.
  5. Burggraaf J, Schoemaker HC, Cohen AF. Assessment of changes in liver blood flow after food intake–comparison of ICG clearance and echo-Doppler. Br J Clin Pharmacol 42: 499–502, 1996.[CrossRef][Web of Science][Medline]
  6. Cornett JA, Herr MD, Gray KS, Smith MB, Yang QX, Sinoway LI. Ischemic exercise and the muscle metaboreflex. J Appl Physiol 89: 1432–1436, 2000.[Abstract/Free Full Text]
  7. Crisafulli A, Scott AC, Wensel R, Davos CH, Francis DP, Pagliaro P, Coats AJ, Concu A, Piepoli MF. Muscle metaboreflex-induced increases in stroke volume. Med Sci Sports Exerc 35: 221–228, 2003.
  8. Ebert TJ, Smith JJ, Barney JA, Merrill DC, Smith GK. The use of thoracic impedance for determining thoracic blood volume changes in man. Aviat Space Environ Med 57: 49–53, 1986.[Medline]
  9. Eldridge FL, Millhorn DE, Kiley JP, Waldrop TG. Stimulation by central command of locomotion, respiration and circulation during exercise. Respir Physiol 59: 313–337, 1985.[CrossRef][Web of Science][Medline]
  10. Freund PR, Hobbs SF, Rowell LB. Cardiovascular responses to muscle ischemia in man–dependency on muscle mass. J Appl Physiol 45: 762–767, 1978.[Abstract/Free Full Text]
  11. Geddes LA, Baker LE. Detection of physiological events by impedance. In: Principles of Applied Biomedical Instrumentation. New York: Wiley, 1989, p. 594–600.
  12. Geddes LA, Kidder H. Specific resistance of blood at body temperature II. Med Biol Eng 14: 180–185, 1976.[Web of Science][Medline]
  13. Geddes LA, Sadler C. The specific resistance of blood at body temperature. Med Biol Eng 11: 336–339, 1973.[Web of Science][Medline]
  14. Gladwell VF, Fletcher J, Patel N, Elvidge LJ, Lloyd D, Chowdhary S, Coote JH. The influence of small fibre muscle mechanoreceptors on the cardiac vagus in humans. J Physiol 567: 713–721, 2005.[Abstract/Free Full Text]
  15. Hammond RL, Augustyniak RA, Rossi NF, Churchill PC, Lapanowski K, O'Leary DS. Heart failure alters the strength and mechanisms of the muscle metaboreflex. Am J Physiol Heart Circ Physiol 278: H818–H828, 2000.[Abstract/Free Full Text]
  16. He YL, Tanigami H, Ueyama H, Mashimo T, Yoshiya I. Measurement of blood volume using indocyanine green measured with pulse-spectrophotometry: its reproducibility and reliability. Crit Care Med 26: 1446–1451, 1998.[CrossRef][Web of Science][Medline]
  17. Hisdal J, Toska K, Flatebo T, Waaler B, Walloe L. Regulation of arterial blood pressure in humans during isometric muscle contraction and lower body negative pressure. Eur J Appl Physiol 91: 336–341, 2004.[CrossRef][Web of Science][Medline]
  18. Iellamo F, Pizzinelli P, Massaro M, Raimondi G, Peruzzi G, Legramante JM. Muscle metaboreflex contribution to sinus node regulation during static exercise: insights from spectral analysis of heart rate variability. Circulation 100: 27–32, 1999.
  19. Iijima T, Aoyagi T, Iwao Y, Masuda J, Fuse M, Kobayashi N, Sankawa H. Cardiac output and circulating blood volume analysis by pulse dye- densitometry. J Clin Monit 13: 81–89, 1997.[CrossRef][Web of Science][Medline]
  20. Kaufman MP. Has the phoenix risen? J Physiol 548: 666, 2003.[Free Full Text]
  21. Kaufman MP, Forster HV. Reflexes controlling circulatory, ventilatory and airway responses to exercise. In: Handbook of Physiology. Exercise: Regulation and Integration of Multiple Systems. Bethesda, MD: Am. Physiol. Soc., 1996, sect. 12, chapt 10, p. 381–447.
  22. Kaufman MP, Rybicki KJ. Discharge properties of group III and IV muscle afferents: their responses to mechanical and metabolic stimuli. Circ Res 61: I60-I65, 1987.[Medline]
  23. Kaufman MP, Rybicki KJ, Waldrop TG, Ordway GA. Effect of ischemia on responses of group III and IV afferents to contraction. J Appl Physiol 57: 644–650, 1984.[Abstract/Free Full Text]
  24. Kim JK, Sala-Mercado JA, Rodriguez J, Scislo TJ, O'Leary DS. Arterial baroreflex alters strength and mechanisms of muscle metaboreflex during dynamic exercise. Am J Physiol Heart Circ Physiol 288: H1374–H1380, 2005.[Abstract/Free Full Text]
  25. Kluess HA, Wood RH. Heart rate variability and the exercise pressor reflex during dynamic handgrip exercise and postexercise arterial occlusion. Am J Med Sci 329: 117–123, 2005.[CrossRef][Web of Science][Medline]
  26. Kluess HA, Wood RH, Welsch MA. Vagal modulation of the heart and central hemodynamics during handgrip exercise. Am J Physiol Heart Circ Physiol 278: H1648–H1652, 2000.[Abstract/Free Full Text]
  27. Lewis SF, Taylor WF, Bastian BC, Graham RM, Pettinger WA, Blomqvist CG. Haemodynamic responses to static and dynamic handgrip before and after autonomic blockade. Clin Sci (Lond) 64: 593–599, 1983.[Medline]
  28. Mancia G, Parati G, Castiglioni P,and di Rienzo M. Effect of sinoaortic denervation on frequency-domain estimates of baroreflex sensitivity in conscious cats. Am J Physiol Heart Circ Physiol 276: H1987–H1993, 1999.[Abstract/Free Full Text]
  29. McCloskey DI, Mitchell JH. Reflex cardiovascular and respiratory responses originating in exercising muscle. J Physiol 224: 173–186, 1972.[Abstract/Free Full Text]
  30. Momen A, Handly B, Kunselman A, Leuenberger UA, Sinoway LI. Influence of gender and active muscle mass on renal vascular responses during static exercise. Am J Physiol Heart Circ Physiol 291: H121–H126, 2006.[Abstract/Free Full Text]
  31. Momen A, Leuenberger UA, Handly B, Sinoway LI. Effect of aging on renal blood flow velocity during static exercise. Am J Physiol Heart Circ Physiol 287: H735–H740, 2004.[Abstract/Free Full Text]
  32. Momen A, Leuenberger UA, Ray CA, Cha S, Handly B, Sinoway LI. Renal vascular responses to static handgrip: role of muscle mechanoreflex. Am J Physiol Heart Circ Physiol 285: H1247–H1253, 2003.[Abstract/Free Full Text]
  33. Montgomery LD, Hanish HM, Marker RA. An impedance device for study of multisegment hemodynamic changes during orthostatic stress. Aviat Space Environ Med 60: 1116–1122, 1989.[Medline]
  34. Nishiyasu T, Tan N, Morimoto K, Sone R, Murakami N. Cardiovascular and humoral responses to sustained muscle metaboreflex activation in humans. J Appl Physiol 84: 116–122, 1998.[Abstract/Free Full Text]
  35. O'Leary DS. Regional vascular resistance vs. conductance: which index for baroreflex responses? Am J Physiol Heart Circ Physiol 260: H632–H637, 1991.[Abstract/Free Full Text]
  36. O'Leary DS. Autonomic mechanisms of muscle metaboreflex control of heart rate. J Appl Physiol 74: 1748–1754, 1993.[Abstract/Free Full Text]
  37. O'Leary DS, Augustyniak RA. Muscle metaboreflex increases ventricular performance in conscious dogs. Am J Physiol Heart Circ Physiol 275: H220–H224, 1998.[Abstract/Free Full Text]
  38. Pagani M, Lombardi F, Guzzetti S, Rimoldi O, Furlan R, Pizzinelli P, Sandrone G, Malfatto G, Dell'Orto S, Piccaluga E. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res 59: 178–193, 1986.[Abstract/Free Full Text]
  39. Pagani M, Montano N, Porta A, Malliani A, Abboud FM, Birkett C, Somers VK. Relationship between spectral components of cardiovascular variabilities and direct measures of muscle sympathetic nerve activity in humans. Circulation 95: 1441–1448, 1997.
  40. Rothe CF. Reflex control of veins and vascular capacitance. Physiol Rev 63: 1281–1342, 1983.[Free Full Text]
  41. Rowell LB. Human Cardiovascular Control. NY: Oxford University Press, 1993.
  42. Rowell LB, O'Leary DS. Reflex control of the circulation during exercise: chemoreflexes and mechanoreflexes. J Appl Physiol 69: 407–418, 1990.[Abstract/Free Full Text]
  43. Sala-Mercado JA, Hammond RL, Kim JK, Rossi NF, Stephenson LW, O'Leary DS. Muscle metaboreflex control of ventricular contractility during dynamic exercise. Am J Physiol Heart Circ Physiol 290: H751–H757, 2006.[Abstract/Free Full Text]
  44. Schoemaker RC, Burggraaf J, Cohen AF. Assessment of hepatic blood flow using continuous infusion of high clearance drugs. Br J Clin Pharmacol 45: 463–469, 1998.[CrossRef][Web of Science][Medline]
  45. Sheriff DD, Augustyniak RA, O'Leary DS. Muscle chemoreflex-induced increases in right atrial pressure. Am J Physiol Heart Circ Physiol 275: H767–H775, 1998.[Abstract/Free Full Text]
  46. Sinoway LI, Li J. A perspective on the muscle reflex: implications for congestive heart failure. J Appl Physiol 99: 5–22, 2005.[Abstract/Free Full Text]
  47. Stewart JM. Autonomic nervous system dysfunction in adolescents with postural orthostatic tachycardia syndrome and chronic fatigue syndrome is characterized by attenuated vagal baroreflex and potentiated sympathetic vasomotion. Pediatr Res 48: 218–226, 2000.[Web of Science][Medline]
  48. Stewart JM. Pooling in chronic orthostatic intolerance: arterial vasoconstrictive but not venous compliance defects. Circulation 105: 2274–2281, 2002.
  49. Stewart JM, McLeod KJ, Sanyal S, Herzberg G, Montgomery LD. Relation of postural vasovagal syncope to splanchnic hypervolemia in adolescents. Circulation 110: 2575–2581, 2004.
  50. Stewart JM, Medow MS, Montgomery LD. Local vascular responses affecting blood flow in postural tachycardia syndrome. Am J Physiol Heart Circ Physiol 285: H2749–H2756, 2003.[Abstract/Free Full Text]
  51. Stewart JM, Montgomery LD. Reciprocal splanchnic-thoracic blood volume changes during the Valsalva maneuver. Am J Physiol Heart Circ Physiol 288: H752–H758, 2005.[Abstract/Free Full Text]
  52. Waaler BA, Toska K, Eriksen M. Involvement of the human splanchnic circulation in pressor response induced by handgrip contraction. Acta Physiol Scand 166: 131–136, 1999.[CrossRef][Web of Science][Medline]
  53. White DD, Montgomery LD. Pelvic blood pooling of men and women during lower body negative pressure. Aviat Space Environ Med 67: 555–559, 1996.[Medline]
  54. Yamamoto K, Kawada T, Kamiya A, Takaki H, Sugimachi M, Sunagawa K. Static interaction between muscle mechanoreflex and arterial baroreflex in determining efferent sympathetic nerve activity. Am J Physiol Heart Circ Physiol 289: H1604–H1609, 2005.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
I. Taneja, M. S. Medow, J. L. Glover, N. K. Raghunath, and J. M. Stewart
Increased vasoconstriction predisposes to hyperpnea and postural faint
Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H372 - H381.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. M. Stewart, I. Taneja, and M. S. Medow
Reduced central blood volume and cardiac output and increased vascular resistance during static handgrip exercise in postural tachycardia syndrome
Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1908 - H1917.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
J. K. Shoemaker, L. Mattar, P. Kerbeci, S. Trotter, P. Arbeille, and R. L. Hughson
WISE 2005: stroke volume changes contribute to the pressor response during ischemic handgrip exercise in women
J Appl Physiol, July 1, 2007; 103(1): 228 - 233.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. A. Sala-Mercado, M. Ichinose, R. L. Hammond, T. Ichinose, M. Pallante, L. W. Stephenson, D. S. O'Leary, and F. Iellamo
Muscle metaboreflex attenuates spontaneous heart rate baroreflex sensitivity during dynamic exercise
Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2867 - H2873.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
I. Taneja, C. Moran, M. S. Medow, J. L. Glover, L. D. Montgomery, and J. M. Stewart
Differential effects of lower body negative pressure and upright tilt on splanchnic blood volume
Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1420 - H1426.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
292/1/H215    most recent
00681.2006v1
Right arrow Alert me when this article is cited
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 Web of Science
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 Web of Science (5)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stewart, J. M.
Right arrow Articles by Medow, M. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stewart, J. M.
Right arrow Articles by Medow, M. S.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.