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Department of Anesthesiology and General Clinical Research Center, Mayo Clinic and Foundation, Rochester, Minnesota 55905
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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We conducted a series of studies to develop and
test a rapid, noninvasive method to measure limb venous compliance in
humans. First, we measured forearm volume (mercury-in-Silastic strain gauges) and antecubital intravenous pressure during inflation of a
venous collecting cuff around the upper arm. Intravenous pressure fit
the regression line, 
0.3 ± 0.7 + 0.95 ± 0.02 · cuff pressure
(r = 0.99 ± 0.00), indicating cuff
pressure is a good index of intravenous pressure. In subsequent
studies, we measured forearm and calf venous compliance by inflating
the venous collecting cuff to 60 mmHg for 4 min, then decreasing cuff
pressure at 1 mmHg/s (over 1 min) to 0 mmHg, using cuff
pressure as an estimate of venous pressure. This method produced
pressure-volume curves fitting the quadratic regression (
limb
volume) = 
0 + 1 · (cuff pressure) + 2 · (cuff
pressure)2, where is change.
Curves generated with this method were reproducible from day to day
(coefficient of variation: 4.9%). In 11 subjects we measured venous
compliance via this method under two conditions: with and without (in
random order) superimposed sympathetic activation (ischemic handgrip
exercise to fatigue followed by postexercise ischemia). Calf
and forearm compliance did not differ between control and sympathetic
activation (P > 0.05); however, the
data suggest that unstressed volume was reduced by the maneuver. These studies demonstrate that venous pressure-volume curves can be generated
both rapidly and noninvasively with this technique. Furthermore, the
results suggest that although whole-limb venous compliance is under
negligible sympathetic control in humans, unstressed volume can be
affected by the sympathetic nervous system.
sympathetic nervous system; orthostasis; hemodynamics; unstressed volume
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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LIMB VENOUS COMPLIANCE is considered a major determinant of the venous pooling that is known to occur in the legs during orthostatic stress. Recently, Halliwill et al. (8) demonstrated that during lower body negative pressure (LBNP), venous pooling in the legs has a greater hemodynamic impact than pooling in the abdomen. This observation emphasizes the importance of the limb veins in orthostatic responses. Indeed, a long-standing concept is that individuals with high vascular compliance in the legs will have increased venous pooling and hence be less tolerant to orthostatic stress (12). However, the factors that influence and determine limb venous compliance in humans remain poorly characterized.
Convertino and colleagues (4) have suggested that muscle mass is the major determinant of leg compliance. In support of this notion, short-term loss of muscle mass (i.e., bed rest atrophy) results in an increase in leg compliance (3, 13). A complementary observation is that LBNP tolerance increases after 12 wk of resistance training (11). These results suggest that short-term interventions that alter leg muscle mass can change leg venous compliance and LBNP tolerance. However, in individuals not undergoing interventions specifically associated with alterations in muscle mass (e.g., bed rest or resistance training), leg muscle mass does not appear to be a major determinant of LBNP tolerance in either men or women (10). This suggests that factors other than, or in addition to, muscle mass may influence limb venous compliance and, subsequently, orthostatic tolerance. One such factor may be sympathetic innervation of the veins. It remains unclear to what degree the sympathetic nervous system controls limb venous compliance in humans (17), due in part to the difficulties involved in measuring limb venous compliance during sympathoexcitatory maneuvers.
Present noninvasive methods for estimation of limb venous compliance in humans have major limitations. First, most require considerable amounts of time and thus do not lend themselves to the study of compliance during brief sympathoexcitatory maneuvers. Second, most methods deal inadequately with the hysteresis seen in limb volume during changes in venous pressure. In this context, hysteresis refers to the considerable discordance between limb volumes measured during a rise in venous pressure vs. a fall in venous pressure. In other words, the relationship between pressure and volume is shifted to higher volumes after a period of venous distension. This phenomenon is generally attributable to interstitial fluid accumulation that may occur during elevations in venous pressure (as a result of increased capillary leak) but may also be due to venous wall "creep" during maintenance of high venous pressure. Third, most methods make the unsubstantiated assumption that resting venous pressure in the limb equals zero. Therefore, we conducted several studies with the goal of developing and testing a rapid, noninvasive method to measure whole-limb venous compliance in humans. In addition, we applied this technique to assess the extent to which increases in sympathetic outflow can decrease whole-limb venous compliance in humans.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Twenty-two healthy, normotensive, nonsmoking subjects (11 women and 11 men) between the ages of 20 and 40 yr volunteered for the following studies. Some subjects participated in several protocols. These studies were approved by the Institutional Review Board, and each subject gave informed consent before participation.
Measurement Techniques
Venous compliance plethysmography. Changes in limb volume were measured with mercury-in-Silastic strain gauges (model EC4, D. E. Hokanson, Bellevue, WA). The strain gauges were electronically calibrated in situ by using circuitry developed by Hokanson et al. (9) that produces a 1% rise in gauge resistance. This change in resistance is equivalent to a 0.5% increase in gauge length, or limb circumference, and thus is proportional to a 1% rise in limb volume (21). Changes in limb volume were expressed as milliliters per deciliter of tissue. For studies of the forearm, a venous collecting cuff was placed around the upper arm 5 cm proximal to the antecubital crease, and the strain gauge was placed around the forearm 5 cm distal to the antecubital crease. For studies of the calf, a venous collecting cuff was placed around the thigh proximal to the knee, and the strain gauge was placed around the calf at the point of maximum girth. The collecting cuffs use low-volume, circumferential air bladders (Zimmer, Dover, OH). Pressure in the venous collecting cuff was measured with a pressure transducer connected to the cuff via an airway. Both transducers were calibrated before the experimental protocol, and the calibrations were verified after the protocol.
Intravenous pressure. A 22-gauge, 5-cm antecubital venous catheter was placed in the forearm that was used for venous collection plethysmography. The catheter was connected to a pressure transducer and flushed continuously at 3 ml/h with saline containing heparin (2 U/ml). This system has been used extensively for intra-arterial pressure measurements (7). The transducer system was identical to that used to measure pressure in the venous collection cuff.
Protocols
Study I: Relationship between venous collection pressure and intravenous pressure. The rationale for this study was to test the assumptions regarding changes in intravenous pressure during manipulation of collecting cuff pressure that form the theoretical basis for all presently available noninvasive methods of assessing whole-limb venous compliance.
Seven subjects (3 women and 4 men) were instrumented for forearm plethysmography and antecubital intravenous pressure measurement. Subjects were studied supine, with the arm slightly above heart level. After 15 min of quiet rest, forearm venous compliance was measured by three methods. First, venous compliance was measured by the technique developed by Robinson and Wilson (15). The venous collecting cuff was inflated to 60 mmHg, and sufficient time was allowed for intravenous pressure to rise to that level (55-215 s). Collection pressure was then decreased at 1 mmHg/s (over 1 min) to 0 mmHg while the resulting drop in intravenous pressure and forearm volume was recorded. Second, compliance was measured by a modified version of the technique described by Buckey et al. (1). The venous collecting cuff was inflated, in sequence, to 20, 40, 50, and 60 mmHg and back down in 2-min intervals. Third, compliance was measured by a modified version of the technique described by Melchior and Fortney (13). The collecting cuff was inflated to the same pressures as in the previous method (20, 40, 50, and 60 mmHg) for 2 min each but returned directly to 0 mmHg between each step (i.e., discontinuous pressure steps). At the end of the protocol, forearm blood flow was measured by venous occlusion plethysmography as described previously (14).Study II: Comparison of forearm and calf compliance by using a new technique and the effect of interstitial fluid accumulation on compliance estimates. The rationale for this study was to test a key remaining assumption that underlies our modified method to estimate whole-limb venous compliance. Specifically, we tested the assumption that interstitial fluid accumulation (edema) does not alter venous compliance by changing the mechanical properties of the tissue surrounding the veins.
Nine subjects (5 women and 4 men) were instrumented for simultaneous forearm and calf venous collection plethysmography. Subjects were studied supine with the arm and leg slightly above heart level. Venous compliance was measured by a modified version of the technique developed by Robinson and Wilson (15). The method was modified 1) by using cuff pressure as an estimate of intravenous pressure and 2) by analyzing the data with a quadratic regression model. After 15 min of quiet rest, forearm and calf venous compliance were measured by inflating the venous collecting cuff to 60 mmHg for 4 min, then decreasing cuff pressure at 1 mmHg/s (over 1 min) to 0 mmHg. After several minutes of rest, the procedure was repeated with the following modification: the 4-min period at 60 mmHg was extended to 8 min in an effort to augment interstitial fluid accumulation. On 2 subsequent days, four of the subjects (2 women and 2 men) repeated this procedure for an assessment of day-to-day reproducibility.Study III: Effect of mechanical compression on compliance. The rationale for this study was to test the hypothesis that externally applied compression decreases whole-limb venous compliance.
Five subjects (2 women and 3 men) were instrumented for calf venous collection plethysmography. Subjects were supine with the leg slightly above heart level. After 15 min of quiet rest, calf venous compliance was measured twice by inflating the venous collecting cuff to 60 mmHg for 4 min, then decreasing cuff pressure at 1 mmHg/s (over 1 min) to 0 mmHg. This was done, in random order, with or without placement of an elastic compression stocking (T. E. D. Anti-Embolism Stocking, Kendall Healthcare Products, Mansfield, MA) on the calf being studied.Study IV: Effect of sympathetic activation on compliance. The rationale for this study was to test the hypothesis that increases in sympathetic outflow to the skeletal muscle vasculature decrease whole-limb venous compliance.
Eleven subjects (6 women and 5 men) were instrumented for calf and forearm venous collection plethysmography. Subjects were supine with the leg and arm slightly above heart level. After 15 min of quiet rest, calf and forearm venous compliance were measured twice by inflating the venous collecting cuffs to 60 mmHg for 4 min, then decreasing cuff pressure at 1 mmHg/s (over 1 min) to 0 mmHg. This was done, in random order, with or without superimposed activation of the muscle pressor reflex. The muscle pressor reflex was activated by having the subject perform ischemic, rhythmic handgrip exercise to fatigue followed by 1 min of ischemia. Exercise was performed with the dominant arm and a commercially available spring-loaded handgrip-strengthening device. Compliance was measured in the contralateral arm and leg. Subjects were allowed to select their own rate of handgripping. For the 4-min compliance trials, exercise was initiated 2 min after inflation of the venous collecting cuffs to 60 mmHg. By the end of the 4-min venous collection period, all but one subject (subject 6) had reached fatigue and were undergoing postexercise ischemia. In subject 6, the venous collection period (60 mmHg) was extended 20 s (i.e., total time 4 min 20 s) until the subject fatigued. In addition to these two compliance trials, a subset of five subjects (3 women and 2 men) had compliance measured twice by inflating the venous collecting cuffs to 60 mmHg for 8 min, then decreasing cuff pressure at 1 mmHg/s (over 1 min) to 0 mmHg. This was done, in random order, with or without superimposed activation of the muscle pressor reflex. In other words, this group of five subjects underwent compliance measurements under four conditions: 1) a 4-min trial with the muscle pressor reflex, 2) a 4-min trial without the muscle pressor reflex, 3) an 8-min trial with the muscle pressor reflex, and 4) an 8-min trial without the muscle pressor reflex. For the 8-min compliance trials, exercise was initiated 6 min after inflation of the venous collecting cuffs to 60 mmHg. By the end of the 8-min venous collection period, all subjects had reached fatigue and were undergoing postexercise ischemia. Postexercise ischemia was maintained while venous collecting pressure was decreased from 60 to 0 mmHg.Data Analysis
Data were digitized and stored on a computer at 50 Hz. Data were analyzed off-line with signal-processing software (WinDaq, Dataq Instruments, Akron, OH).Statistics
For study I, the relationship between venous collection pressure and intravenous pressure was assessed as follows. A linear regression between collection cuff and intravenous pressures measured at the end of each 2-min stage of ascending and descending pressures was performed for each subject. Because intravenous pressure was clearly not equal to cuff pressure under resting conditions (no cuff inflation), this time point was not included in the regression (i.e., only 20-, 40-, 50-, and 60-mmHg cuff inflations were included). Similarly, a linear regression between collection and intravenous pressures measured while collection pressure was decreased from 60 to 10 mmHg at 1 mmHg/s was performed for each subject. The slopes and intercepts of the regressions between collection and intravenous pressures were compared with that of the line of identity (slope of 1, intercept of 0) by a univariate t-test.A limited comparison of compliance estimates from the various methods used in study I was performed as follows. Compliance estimates were calculated as the change in limb volume from a collecting cuff pressure of 20 mmHg to a pressure of 40 mmHg. These were calculated for five different methods: 1) decreasing pressure at 1 mmHg/s; 2) a pressure step up from 20 to 40 mmHg; 3) a pressure step down from 40 to 20 mmHg; 4) a discontinuous pressure step up from 20 to 40 mmHg (i.e., returning to 0 mmHg between steps); and 5) for a discontinuous pressure step down from 40 to 20 mmHg.
For studies II,
III, and
IV, pressure-volume curves were
generated from the pressure-volume relationship as pressure was
decreased at 1 mmHg/s from 60 to 10 mmHg. Data below 10 mmHg were
excluded due to the ambiguity of true intravenous pressure at low cuff pressures. Pressure-volume curves were compared by means of the quadratic regression model (limb volume) = 0 + 1 · (cuff
pressure) + 2 · (cuff
pressure)2, where is change.
For the model, limb volume was equal to limb volume at a given cuff
pressure minus baseline limb volume (i.e., before cuff inflation). As
such, 0 is a complicated
variable that is affected by several factors. First, because there is a volume associated with the resting venous pressure,
0 in part reflects the volume
difference between resting venous pressure and zero pressure. Second,
0 will reflect any hysteresis
that occurs during the compliance measurement. This may be secondary to
either venous wall creep or capillary leak and associated interstitial fluid accumulation. Last, 0
will reflect any change in unstressed volume that occurs within a
compliance measurement. As such, a change in
0 or vertical shift in a
pressure-volume curve is difficult to interpret. In addition, because
the pressure-volume relationship is not a straight line, a single
number is not sufficient to characterize the slope of the
pressure-volume curve. Thus the group-average regression parameters
1 and
2 were used together as an
estimate of compliance, such that compliance = 1 + 2 · 2 · (cuff
pressure). In other words, compliance was defined as the derivative of
the pressure-volume curve. The resulting pressure-dependent
"compliance lines" were evaluated graphically. Regression models
were calculated by using the SAS GLM procedure (SAS v6.09, SAS
Institute, Cary, NC). For each trial, data from 60 to 10 mmHg in 2-mmHg
increments were included in the regression. Differences were considered
significant when P < 0.05. All
values are reported as means ± SD, except regression parameters,
which are reported as estimate ± SE of the estimate.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Effect of Venous Collecting Cuff on Intravenous Pressure
Figure 1 shows the relationship between intravenous and cuff pressure. Without pressure in the venous collecting cuff, intravenous pressure was 5.7 ± 1.1 mmHg. When the cuff was inflated above resting intravenous pressure and steady-state pressures were achieved, the slope of the relationship between intravenous pressure and cuff pressure was 0.95 ± 0.02 (P < 0.05 vs. the line of identity), the intercept was0.3 ± 0.7 mmHg (not different from 0), and the correlation coefficient (r) for
the relationship was 0.999 ± 0.000 (P < 0.05). When the
collection pressure was decreased from 60 to 10 mmHg at 1 mmHg/s, the
slope of the relationship between intravenous pressure and cuff
pressure was 0.93 ± 0.02 (P < 0.05 vs. the line of identity), the intercept was 1.5 ± 1.0 mmHg
(P < 0.05 vs. 0), and
r for the relationship was 0.999 ± 0.000 (P < 0.05).
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Figure 2 shows the change in volume in one
subject as intravenous pressure increased to 60 mmHg over several
minutes (214 s) and then decreased to 7 mmHg (at 1 mmHg/s). There was a
noticeable degree of hysteresis in this individual and all subjects
studied.
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The rate of intravenous pressure rise during venous collection at 60 mmHg was 0.54 ± 0.36 mmHg/s. On the basis of this, we calculated
that subjects would reach 60 mmHg in ~147 s. The time course was
variable (±68 s) and tended to be related to the magnitude of
resting forearm blood flow (r = 0.557, P = 0.192). Figure
3 shows the representative data from two
subjects, one with a rapid and one with a slow rise in intravenous
pressure with the collecting cuff inflated to 50 mmHg for 2 min. As can
be seen from the tracings, it is difficult to determine from the
plethysmogram at what time intravenous pressure achieves a steady-state
level. In contrast to the slow rate of rise in intravenous pressure
during cuff inflation, intravenous pressure fell to resting levels in
<1 s when the collecting cuff was instantaneously deflated.
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Comparison of Various Compliance Methods
Table 1 shows compliance values derived over the 20- to 40-mmHg pressure range with several compliance methods. There were differences in the values generated by the various methods, and most proved more variable across subjects than was the proposed method of decreasing pressure at 1 mmHg/s. Figure 4 shows the various pressure-volume curves for one individual and highlights the problems inherent in some of the standard methods.
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Effect of Duration of Collection on Compliance Estimate
During study II,0 was greater during the 8-min
collection trial compared with the 4-min collection trial in both the
arm (8 min: 1.58 ± 0.22 vs. 4 min: 0.93 ± 0.23 ml/dl of tissue,
P < 0.05) and leg (8 min: 0.75 ± 0.19 vs. 4 min: 0.30 ± 0.20 ml/dl of tissue,
P < 0.05; see Fig.
5).
1 and
2 did not differ, and thus the
compliance lines are superimposable (Fig.
5B). Thus, although the curves were
shifted to higher volumes by the extended venous collection period,
there was no effect on compliance.
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Forearm vs. Calf Compliance
0 in the arm was greater than
in the leg (e.g., with 4-min collection period, arm: 0.93 ± 0.23 vs. leg: 0.30 ± 0.20 ml/dl of tissue,
P < 0.05). Pressure-volume curves in
the leg were steeper than in the arm
(P < 0.05; Fig.
6A);
thus, compliance was higher in the leg than in the arm (Fig.
6B). During repeated trials on 2 separate days, the coefficient of variation for compliance was 4.9%.
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External Compression
0 was dramatically reduced by
application of external compression to the leg (compression:
1.84 ± 0.66 vs. control: 0.68 ± 0.48 ml/dl of tissue,
P < 0.05). It must be noted that for
this particular application, all values for limb volume are relative to
resting limb volume without external compression. The slope of the
curve was also dramatically altered by external compression (P < 0.05; Fig.
7A);
surprisingly, compliance was increased by external compression (Fig.
7B).
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Sympathetic Activation
In the group of 11 subjects who underwent ischemic handgrip exercise and postexercise ischemia,0 was less during sympathetic activation (postexercise ischemia in the contralateral forearm) in both the arm (exercise: 0.54 ± 0.20 vs. control: 0.75 ± 0.20 ml/dl of tissue, P < 0.05) and leg
(exercise: 0.77 ± 0.24 vs. control: 1.18 ± 0.26 ml/dl of
tissue, P < 0.05).
1 and
2 did not differ. Thus,
although the curves were shifted to lower volumes by
sympathoexcitation, there was no effect on the slope of the pressure-volume curves (Fig. 8,
A and
C) and no effect on compliance (Fig.
8, B and
D). In addition, these effects were
not altered by extension of the venous collection period to 8 min
(n = 5), which equally shifted curves
to higher volumes in both the control and exercise trials without
affecting slopes (data not shown).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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We have developed a new method for estimating venous compliance in the arm or leg on the basis of experimentally determined criteria. Furthermore, we have used this new method to study the effect of physiological and mechanical influences on venous compliance in humans. A novel finding is that sympathoexcitation produced by muscle chemoreflex activation in humans does not appear to alter whole-limb venous compliance but may decrease the unstressed volume of the venous system in the arm and leg.
Development of New Method
Need for new method. There are several problems inherent in most established methods for estimating limb venous compliance in humans. First, most require considerable amounts of time (>20 min) and thus do not lend themselves to the study of compliance during brief sympathoexcitatory maneuvers. This is particularly true of methods that use discontinuous steps in pressure, each of which may take from 2-5 min/step in pressure to reach steady-state pressure levels. Second, most methods deal inadequately with the hysteresis of limb volume during changes in venous pressure. This issue explains a portion of the variability seen in the compliance estimates shown in Table 1 and Fig. 4. The basic problem is that many methods rely on the observer's ability to determine when a plethysmographic tracing has reached steady state after a step increase in collecting cuff pressure. Our data suggest that an observer cannot differentiate between the development of hysteresis and further increases in venous pressure (Fig. 3). This difficulty is overcome to a limited extent by methods that rely on the rapid fall in pressure and volume when cuff pressure is released; however, as mentioned above, such methods are time consuming. The third problem inherent in most established methods is the unsubstantiated assumption that resting venous pressure in the limb equals zero. Our results show this is not the case; resting venous pressure was ~6 mmHg in the subjects we studied. Thus characterizing compliance as the change in limb volume in the transition from no cuff inflation to cuff inflation at a set pressure (e.g., 30 mmHg), as is often done, represents an unknown rise in intravenous pressure and not the presumed 30-mmHg increase. In other words, the baseline volume in most studies occurs at an undefined resting pressure. Our procedure overcomes this by considering the overall slope of the curve independent of resting venous pressure.
Experimental basis for new method. We designed our present method on the basis of the experimental results we obtained in study I. The key observations were the following.
First, resting pressure is not equal to zero but is below 10 mmHg in the majority of healthy individuals (Fig. 1). Thus only the pressure range from 10 to 60 mmHg is analyzed. Second, when the collecting cuff is inflated to 60 mmHg, intravenous pressure will rise to that level when given adequate time (Fig. 1). On the basis of our results with direct intravenous pressure measurements, young healthy individuals reach this pressure within 4 min. However, 4 min may be insufficient in other populations that have either reduced blood flow or increased venous capacity. A simple experiment similar to our study I will determine the amount of time required to reach 60 mmHg in other populations. Third, intravenous pressure will track collecting cuff pressure when cuff pressure drops at a rate of ~1 mmHg/s. Therefore, we analyzed data collected as pressure fell at this rate. The short duration of data collection minimizes and standardizes the effect of hysteresis on the slope of the pressure-volume curve. Furthermore, we conducted study II to test one remaining assumption of our method: that the amount of interstitial fluid accumulation, secondary to increased capillary leak, would not have an impact on the estimation of venous compliance. We found that, even with the additional interstitial fluid accumulation provided by an 8-min venous collection period (twice normal), venous compliance as estimated by our method was reproducible. To test the ability of our methods to detect functional changes in leg venous compliance, we measured compliance in subjects wearing elastic compression (i.e., antithrombosis) stockings. Our results suggest that external compression with elastic stockings reduces venous pooling, but only at low levels of venous pressure. When venous pressure was increased (as it would on standing), there were no discernable differences in limb volume. Thus, although venous volume in the legs would be reduced while supine, the actual rise in volume during the transition from supine to standing would be augmented in an individual wearing elastic stockings. We suggest that other mechanical measures used to reduce venous pooling during orthostasis should be tested in this manner.Limitations of New Method
Although this method overcomes many of the limitations of previously used whole-limb compliance methods, two potential limitations remain that must be considered when results are interpreted. First, a limitation of this method is that the factors underlying vertical shifts and changes in the regression parameter0 are complicated, and,
therefore, such changes must be interpreted with caution. This will be
illustrated in the discussion below regarding sympathetically mediated
changes in unstressed volume. Second, it is commonly believed that all
whole-limb compliance methods are inferior to isolated-vein methods or
constant-flow preparations in animal models because of the impact of
changes in blood flow on postcapillary venous pressures. Rowell (18)
and Rothe (17) have extensively discussed this issue. The major concern
is that vasoconstriction has the potential of mimicking the effect of
active venoconstriction by reducing pressure in the small postcapillary
venules (relative to that in the larger conduit veins). However, this
effect may be less important when compliance is measured over a high
range of pressures (e.g., 10-60 mmHg), because most of the change
in venous volume that occurs in this pressure range is in the larger conduit veins (2). Because any effect of vasoconstriction on the
postcapillary venous pressures should be less when the pressure in the
large veins is held at 60 mmHg than when it is at 10 mmHg (i.e., back
pressure at 60 mmHg should reduce any venule-to-vein pressure gradient
to a greater extent than back pressure at 10 mmHg), we would predict
that the observed effect would be an increase in the slope of the
pressure-volume curve. In other words, limb volume would be affected
(reduced) only at low pressures and not affected at high pressures. As
can be seen in Fig. 8, this was not observed during our
sympathoexcitatory maneuver (which is known to cause vasoconstriction).
This suggests that changes in blood flow on postcapillary venous
pressures may have less impact on this measure of whole-limb venous
compliance than anticipated. Nonetheless, this limitation should be
considered when the results obtained with this method are interpreted.
Regulation of Compliance
Using our new method, we could not demonstrate a change in venous compliance during the profound sympathoexcitation produced by activation of the muscle chemoreflex. Earlier work by Zelis and Mason (22) suggested that, in the forearm, only cutaneous veins are under sympathetic control. This observation was based on complicated invasive pharmacological and physiological studies. Along these lines, our sympathoexcitatory stimulus is known to increase sympathetic outflow to muscle vascular beds. As such, our data are consistent with the observations of Zelis and Mason, that forearm muscle venous compliance is not responsive to sympathetic control. Furthermore, our data support the generalization of this statement to the leg muscle vasculature.In contrast to the effect on compliance, we found that pressure-volume
curves in the arm and leg are shifted downward (to lower limb volumes)
by sympathoexcitation (as reflected in Fig. 8, and by the reduction in
the regression parameter 0).
As such, it is important to discuss the physiological meaning and
interpretation of these shifts. As mentioned above,
0 is a complicated variable that is affected by the volume associated with the resting venous pressure, fluid leak and fluid accumulation that occur during the
compliance trial, and any change in unstressed volume of the limb veins
that occurs during the trial. Thus several distinct mechanisms might
underlie the shift produced by sympathoexcitation.
Because the changes in limb volume are relative to a resting volume and pressure measured before our sympathetic maneuver, any effect of increased sympathetic activity on resting venous pressure would not explain the vertical shift in the pressure-volume curve that was observed. It is possible that fluid leak from the intravascular space was decreased by sympathetic nerve activity and accounted for the changes we observed after the 4-min compliance trials. Increased sympathetic activity occurred during roughly one-half the time allotted for venous collection (4 min) during these trials, and thus it seems plausible that reduced blood flow during this time decreased the venous pressure profile over the 4-min period and resulted in a lesser degree of fluid accumulation. However, when the response to sympathoexcitation observed after the 4-min compliance trial is compared with that after the 8-min compliance trial, this explanation seems unlikely. During the longer compliance trials, the venous pressure profile should be the same with and without sympathoexcitation because all subjects would have achieved a distending pressure of 60 mmHg before the onset of exercise. Because the shift in the pressure-volume curve caused by sympathoexcitation was the same in both the short and the longer compliance trials, it suggests that changes in the venous pressure profile (and subsequent changes in fluid accumulation) do not play a role in these curve shifts. A more likely explanation is that sympathetic activation leads to a reduction in the unstressed volume of the veins in both the arm and leg. This is consistent with prior studies in animals and isolated leg veins that have demonstrated a reduction in venous unstressed volume with little or no change in compliance (5, 6, 16, 19, 20). To the best of our knowledge, this is the first instance in which this has been demonstrated in humans.
Perspectives
We were surprised that sympathetic activation did not alter limb venous compliance in humans but appears to reduce the unstressed volume. The implication of this observation is that the sympathetic nervous system, the body's primary defense against a fall in arterial pressure during orthostatic stress, has only a limited ability to directly affect the degree to which blood pools in dependent veins during orthostasis. For example, if one assumes a leg muscle mass of 18 kg (10), the change in unstressed volume we observed (~0.5 ml/dl of tissue) would reduce venous pooling ~90 ml during orthostatic stress. We must next ask, What other factors dominate pooling of blood during orthostasis to afford us protection against this daily stress? It would seem that in the absence of active changes in venous compliance, passive changes in venous capacity secondary to changes in vascular resistance play a major role in tolerance to orthostatic stress (18).These observations further highlight the importance of the muscle pump in reducing the accumulation of blood in the dependent veins during standing. As such, mechanical measures may prove much more effective in treating orthostatic intolerance than methods targeted toward increasing intrinsic regulation of compliance.
Conclusions
We have presented a novel method for the noninvasive estimation of whole-limb venous compliance that is based on experimentally determined criteria. Using this method, we have found that neither forearm nor calf venous compliance is under functional sympathetic regulation but that changes in unstressed volume may be mediated by the sympathetic nervous system.| |
ACKNOWLEDGEMENTS |
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We thank Latoya T. Berry, Sarah E. Hager, and Cara J. Weisbrod for technical assistance and Dr. David N. Proctor for insightful suggestions. We especially thank the subjects who volunteered for these studies. Finally, we thank the reviewers for constructive criticism of the manuscript.
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FOOTNOTES |
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These studies were supported by National Institutes of Health Grants M01-RR-00585, NS-32352, HL-46493, DK-09826, and HL-10123; the Glen L. and Lyra M. Ebling Cardiology Research Endowment; and the Mayo Foundation.
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 and other correspondence: J. R. Halliwill, Anesthesia Research, Mayo Clinic, 200 1st St. SW, Rochester, MN 55905 (E-mail: halliwill.john{at}mayo.edu).
Received 22 October 1998; accepted in final form 18 June 1999.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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1.
Buckey, J. C.,
L. D. Lane,
G. Plath,
F. A. Gaffney,
F. Baisch,
and
C. G. Blomqvist.
Effects of head-down tilt for 10 days on the compliance of the leg.
Acta Physiol. Scand.
144:
53-60,
1992.
2.
Buckey, J. C.,
R. M. Peshock,
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, Steady-state values; 
, values as pressure was decreased at 1 mmHg/s; dashed line, line of identity; solid lines, lines of
regression.
, Downward pressure
ramp at 1 mmHg/s; 
, discontinuous pressure steps up; 
,
discontinuous pressure steps down. Both continuous methods (circles)
show marked effects of hysteresis at higher pressures, whereas both
discontinuous methods (squares) reflect that insufficient time was
available for intravenous pressure to reach 50 and 60 mmHg in this
individual.
