On the edema-preventing effect of the calf muscle pump

During motionless standing an increased hydrostatic pressure leads to increased transcapillary fluid filtration into the interstitial space of the tissues of the lower extremities. The resulting changes in calf volume were measured using a mercury-in-silastic strain gauge. Following a change in body posture from lying to standing or sitting a two-stage change in calf volume was observed. A fast initial filling of the capacitance vessels was followed by a slow but continuous increase in calf volume during motionless standing and sitting with the legs dependent passively. The mean rates of this slow increase were about 0.17%.min-1 during standing and 0.12%.min-1 during sitting, respectively. During cycle ergometer exercise the plethysmographic recordings were highly influenced by movement artifacts. These artifacts, however, were removed from the recordings by low-pass filtering. As a result the slow volume changes, i.e. changes of the extravascular fluid were selected from the recorded signal. Contrary to the increases during standing and sitting the calf volumes of all 30 subjects decreased during cycle ergometer exercise. The mean decrease during 18 min of cycling (2-20 min) was -1.6% at 50 W work load and -1.9% at 100 W, respectively. This difference was statistically significant (p less than or equal to 0.01). The factors which may counteract the development of an interstitial edema, even during quiet standing and sitting, are discussed in detail. During cycling, however, three factors are most likely to contribute to the observed reduction in calf volume: (1) The decrease in venous pressure, which in turn reduces the effective filtration pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional extravascular density of the lung in patients with acute pulmonary edema

The regional distribution of extravascular lung density (lung tissue and interstitial or alveolar fluid per unit thoracic volume) and fractional pulmonary blood volume (volume of blood per unit thoracic volume) was measured in five patients with acute interstitial pulmonary edema and two patients with acute alveolar edema. We found a uniform increase in extravascular lung density in the patients with acute interstitial edema but a preferentially dependent distribution in the patients with alveolar edema. Fractional blood volume had an abnormally uniform distribution in patients with interstitial edema. In alveolar edema, there was marked redistribution of blood volume away from severely edematous regions. The results are in agreement with previous experimental work with animal models. The distribution of extravascular lung density and fractional blood volume in subjects with acute interstitial edema is, however, different from that found in subjects with chronic interstitial edema, suggesting that the pathophysiological characteristics of the two conditions may be different.     

Slow volume changes in calf and thigh during cycle ergometer exercise

To study the transcapillary fluid movements in the human lower limb in the upright body position and during muscle exercise, the slow changes in thigh and calf volumes were measured by mercury-in-rubber-strain gauge plethysmography. Measurements were carried out on 20 healthy volunteers while sitting, standing and doing cycle ergometer exercise at intensities of 50 and 100-W. A plethysmographic recording of slow extravascular volume changes during muscle exercise was possible because movement artefacts were eliminated by low-pass filtering. While standing and sitting the volumes of both thigh and calf increased due to enhanced transcapillary filtration. While standing the mean rate of increase was 0.13%.min-1 in the calf and 0.09%.min-1 in the thigh. During cycle ergometer exercise at 50 and 100 W, the calf volume decreased with a mean rate of -0.09.min-1. In contrast, the thigh volume did not change significantly during exercise at 50 W and increased at 100 W. Most of the increase occurred during the first half of the experimental period i.e. between min 2 and 12, amounting to +0.6%. Thus, simultaneous measurements revealed opposite changes in the thigh and calf. This demonstrates that the conflicting findings reported in the literature may have occurred because opposite changes can occur in different muscle groups of the working limb at the same time. Lowered venous pressure, increased lymph flow and increased tissue pressure in the contracting muscle are considered to have caused the reduction in calf volume during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

The interstitial fluid content in working muscle modifies the cardiovascular response to exercise

The volume of interstitial fluid in the limbs varies considerably, due to hydrostatic effects. As signals from working muscle, responsible for much of the cardiovascular drive, are assumed to be transmitted in this compartment, blood pressure and heart rate could be affected by local or systemic variations in interstitial hydration. Using a special calf ergometer, eight male subjects performed rhythmic aerobic plantar flexions in a supine position with dependent calves for periods of 7 min. During exercise heart rate, blood pressure, oxygen uptake (VO2) and blood lactate concentrations were measured in two different tests, one before and after interstitial calf dehydration through limb elevation for 25 min, compared to the other, a control with unaltered fluid volume in a maintained working position. Impedance plethysmography showed calf volume to be stabilized in the control position. Leg elevation by passive hip flexion to 90 degrees resulted in a fast (vascular) volume decrease lasting less than 2 min, followed by a slow linear fluid loss from the interstitial compartment. Then, when returned to the control position, adjustment of vascular volume was completed within 2 min and exercise could be performed with dehydration remaining in the interstitium only. Cardiovascular response was identical at the start of both tests. However, exercising with dehydrated calves elicited a significantly larger increase in heart rate compared to the control, whereas VO2 was identical. The blood pressure response was shown to be only slightly enhanced. Structural interstitial features varying with hydration, most likely chemical or mechanical ones, may have been responsible for this amplification of signals.     

Regional extravascular and interstitial lung water in normal dogs

We measured the regional distribution of pulmonary extravascular and interstitial water to examine the possibility that regional differences in microvascular pressure or tissue stress may cause regional differences in lung water. We placed chloralose-anesthetized dogs in an upright (n = 6) or supine (n = 7) position for 180 min. We injected 51Cr-labeled EDTA to equilibrate to the extracellular space and 125I-labeled albumin to equilibrate with plasma. At the end of the experiment, the lungs were removed, passively drained of blood, and inflated before rapid freezing. Lungs were divided into horizontal slices, and extravascular, interstitial, and plasma water, red cell volume, and dry lung weight were determined for each slice. We found that regional extravascular and interstitial water were constant throughout the lungs in both groups and that there were no significant differences between upright and supine dogs. There were no significant differences in hematocrit between slices. We conclude that gravity and body position have no measurable effect on either the total size of the extravascular and interstitial compartments or their regional distribution.     

Regional blood volume and peripheral blood flow in postural tachycardia syndrome

Variants of postural tachycardia syndrome (POTS) are associated with increased ["high-flow" POTS (HFP)], decreased ["low-flow" POTS (LFP)], and normal ["normal-flow" POTS (NFP)] blood flow measured in the lower extremities while subjects were in the supine position. We propose that postural tachycardia is related to thoracic hypovolemia during orthostasis but that the patterns of peripheral blood flow relate to different mechanisms for thoracic hypovolemia. We studied 37 POTS patients aged 14-21 yr: 14 LFP, 15 NFP, and 8 HFP patients and 12 healthy control subjects. Peripheral blood flow was measured in the supine position by venous occlusion strain-gauge plethysmography of the forearm and calf to subgroup patients. Using indocyanine green techniques, we showed decreased cardiac index (CI) and increased total peripheral resistance (TPR) in LFP, increased CI and decreased TPR in HFP, and unchanged CI and TPR in NFP while subjects were supine compared with control subjects. Blood volume tended to be decreased in LFP compared with control subjects. We used impedance plethysmography to assess regional blood volume redistribution during upright tilt. Thoracic blood volume decreased, whereas splanchnic, pelvic, and leg blood volumes increased, for all subjects during orthostasis but were markedly lower than control for all POTS groups. Splanchnic volume was increased in NFP and LFP. Pelvic blood volume was increased in HFP only. Calf volume was increased above control in HFP and LFP. The results support the hypothesis of (at least) three pathophysiologic variants of POTS distinguished by peripheral blood flow related to characteristic changes in regional circulations. The data demonstrate enhanced thoracic hypovolemia during upright tilt and confirm that POTS is related to inadequate cardiac venous return during orthostasis.     

Blood flow to contracting human muscles: influence of increased sympathetic activity

The purpose of this study was to examine the effects of the increased sympathetic activity elicited by the upright posture on blood flow to exercising human forearm muscles. Six subjects performed light and heavy rhythmic forearm exercise. Trials were conducted with the subjects supine and standing. Forearm blood flow (FBF, plethysmography) and skin blood flow (laser Doppler) were measured during brief pauses in the contractions. Arterial blood pressure and heart rate were also measured. During the first 6 min of light exercise, blood flow was similar in the supine and standing positions (approximately 15 ml.min-1.100 ml-1); from minutes 7 to 20 FBF was approximately 3-7 ml.min-1.100 ml-1 less in the standing position (P less than 0.05). When 5 min of heavy exercise immediately followed the light exercise, FBF was approximately 30-35 ml.min-1.100 ml-1 in the supine position. These values were approximately 8-12 ml.min-1.100 ml-1 greater than those observed in the upright position (P less than 0.05). When light exercise did not precede 8 min of heavy exercise, the blood flow at the end of minute 1 was similar in the supine and standing positions but was approximately 6-9 ml.min-1.100 ml-1 lower in the standing position during minutes 2-8. Heart rate was always approximately 10-20 beats higher in the upright position (P less than 0.05). Forearm skin blood flow and mean arterial pressure were similar in the two positions, indicating that the changes in FBF resulted from differences in the caliber of the resistance vessels in the forearm muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vascular perturbations in the chronic orthostatic intolerance of the postural orthostatic tachycardia syndrome.

Chronic orthostatic intolerance is often related to the postural orthostatic tachycardia syndrome (POTS). POTS is characterized by upright tachycardia. Understanding of its pathophysiology remains incomplete, but edema and acrocyanosis of the lower extremities occur frequently. To determine how arterial and venous vascular properties account for these findings, we compared 13 patients aged 13-18 yr with 10 normal controls. Heart rate and blood pressure were continuously recorded, and strain-gauge plethysmography was used to measure forearm and calf blood flow, venous compliance, and microvascular filtration while the subject was supine and to measure calf blood flow and calf size change during head-up tilt. Resting venous pressure was higher in POTS compared with control (16 vs. 10 mmHg), which gave the appearance of decreased compliance in these patients. The threshold for edema formation decreased in POTS patients compared with controls (8.3 vs. 16.3 mmHg). With tilt, early calf blood flow increased in POTS patients (from 3.4 +/- 0.9 to 12.6 +/- 2.3 ml. 100 ml(-1). min(-1)) but did not increase in controls. Calf volume increased twice as much in POTS patients compared with controls over a shorter time of orthostasis. The data suggest that resting venous pressure is higher and the threshold for edema is lower in POTS patients compared with controls. Such findings make the POTS patients particularly vulnerable for edema fluid collection. This may signify a redistribution of blood to the lower extremities even while supine, accounting for tachycardia through vagal withdrawal.     

Reduction in extracellular muscle volume increases heart rate and blood pressure response to isometric exercise

To investigate the effect of local dehydration on heart rate and blood pressure during static exercise, six healthy male subjects performed exercise of the calf muscles with different extracellular volumes of the working muscles. Exercise consisted of 5 min of static calf muscle contractions at about 10% of maximal voluntary contraction. The body position during exercise was identical in all tests, i.e. supine with the knee joint 90 degrees flexed. During a 25-min pre-exercise period three different protocols were employed to manipulate the calf volume. In test A the subjects rested in the exercise position; in test B the body position was the same as in A but calf volumes were increased by venous congestion [cuffs inflated to 10.67 kPa (80 mmHg)]; in test C the calf volumes were decreased by lifting the calves about 40 cm above heart level with the subjects supine. To clamp the changed calf volumes in tests B and C, cuffs were inflated to 300 mmHg 5 min before the onset of exercise. This occlusion was maintained for 1 min after the termination of exercise. Compared to tests A and B, the reduced volume of test C led to significant increases in heart rate and blood pressure during exercise. Oxygen uptake did not exceed resting levels in tests B and C until the cuffs were deflated, indicating that only calf muscles contributed to the neurogenic peripheral drive. It is concluded that extracellular muscle volume plays a significant role in adjusting heart rate and blood pressure during static exercise.     

Water exchange induced by unilateral exercise in active and inactive skeletal muscles.

Water exchange was evaluated in active (E-leg) and inactive skeletal muscles by using (1)H-magnetic resonance imaging. Six healthy subjects performed one-legged plantar flexion exercise at low and high workloads. Magnetic resonance imaging measured calf cross-sectional area (CSA), transverse relaxation time (T2), and apparent diffusion capacity (ADC) at rest and during recovery. After high workload, inactive muscle decreased CSA and T2 by 2.1% (P < 0.05) and 3.1% (P < 0.05), respectively, and left ADC unchanged. E-leg simultaneously increased CSA, T2, and ADC by 4.2% (P < 0.001), 15.5% (P < 0.05), and 12.5% (P < 0.001), respectively. In conclusion, ADC and T2 correlated highly with muscle volume, indicative of extravascular water displacement closely related to muscle activity and perfusion, which was presumably a combined effect of increased intracellular osmoles and hydrostatic forces as driving forces. A distinguishable muscle temperature release was initially detected in the E-leg after high workload, and the ensuing recovery of ADC and T2 indicated delayed interstitial restitution than restitution of the intracellular compartment. Furthermore, absorption of extravascular water was detected in inactive muscles at contralateral high-intensity exercise.     

Calf blood flow and posture: Doppler ultrasound measurements during and after exercise.

To investigate the joint effects of body posture and calf muscle pump, the calf blood flow of eight healthy volunteers was measured with pulsed Doppler equipment during and after 3 min of rhythmic exercise on a calf ergometer in the supine, sitting, and standing postures. Muscle contractions seriously impeded calf blood flow. Consequently, blood flow occurred mainly between contractions and reached a plateau that lasted at least the final 100 s of each exercise series. After exercise the blood flow decreased much faster in the sitting and standing postures than in the supine posture. There was no difference in blood flow between various postures during the same submaximal exercise. However, subjects in the standing posture were able to perform exercise with a higher load than in the supine posture, and blood flow in the standing posture could become twice as high as in the supine posture. We conclude that calf blood flow is regulated according to needs; available perfusion pressure determined maximal blood flow and exercise; and compared with the supine posture, the standing posture and calf muscle pump increase the perfusion pressure.     

Effect of Gravity on Blood Distribution and Flow in Large Vessels of Healthy Humans

Ultrasound imaging of vessels and flow Doppler ultrasonography were used to study the hemodynamic responses of large arteries and veins to orthostasis in 230 healthy human subjects of both sexes. The arterial system was shown to respond to orthostasis by differentially reducing the blood flow capacity and velocity, especially the blood supply to the lower extremities. During one-leg upright standing, the blood flow in the arterial bed of the weight-bearing leg was redistributed in favor of antigravity calf muscles. No blood flow redistribution was observed in the vertically oriented non-weight-bearing leg. A single voluntary contraction of the triceps surae muscles caused a transient increase in the volume blood flow in the femoral vein (by 2.5- to 5.0-fold in the recumbent position of the body and by 4- to 10-fold in the upright position).     

Influence of hydrostatic pressure gradients on regulation of plasma volume after exercise

The impact of posture on the immediate recoveryof intravascular fluid and protein after intense exercise wasdetermined in 14 volunteers. Forces which govern fluid and proteinmovement in muscle interstitial fluid pressure(P_ISF), interstitial colloid osmotic pressure (COP_i), andplasma colloid osmotic pressure(COP_p) were measured before andafter exercise in the supine or upright position. During exercise,plasma volume (PV) decreased by 5.7 ± 0.7 and 7.0 ± 0.5 ml/kgbody weight in the supine and upright posture, respectively. Duringrecovery, PV returned to its baseline value within 30 min regardless ofposture. PV fell below this level by 60 and 120 min in the supine andupright posture, respectively (P < 0.05). Maintenance of PV in the upright position was associated with adecrease in systolic blood pressure, an increase inCOP_p (from 25 ± 1 to 27 ± 1 mmHg; P < 0.05), and an increasein P_ISF (from 5 ± 1 to 6 ± 2 mmHg), whereas COP_i wasunchanged. Increased P_ISFindicates that the hydrostatic pressure gradient favors fluid movementinto the vascular space. However, retention of the recaptured fluid inthe plasma is promoted only in the upright posture because of increasedCOP_p.

     

Impact of body position on central and peripheral hemodynamic contributions to movement-induced hyperemia: implications for rehabilitative medicine

This study used alterations in body position to identify differences in hemodynamic responses to passive exercise. Central and peripheral hemodynamics were noninvasively measured during 2 min of passive knee extension in 14 subjects, whereas perfusion pressure (PP) was directly measured in a subset of 6 subjects. Movement-induced increases in leg blood flow (LBF) and leg vascular conductance (LVC) were more than twofold greater in the upright compared with supine positions (LBF, supine: 462 ± 6, and upright: 1,084 ± 159 ml/min, P < 0.001; and LVC, supine: 5.3 ± 1.2, and upright: 11.8 ± 2.8 ml·min?1 ·mmHg?1, P < 0.002). The change in heart rate (HR) from baseline to peak was not different between positions (supine: 8 ± 1, and upright: 10 ± 1 beats/min, P = 0.22); however, the elevated HR was maintained for a longer duration when upright. Stroke volume contributed to the increase in cardiac output (CO) during the upright movement only. CO increased in both positions; however, the magnitude and duration of the CO response were greater in the upright position. Mean arterial pressure and PP were higher at baseline and throughout passive movement when upright. Thus exaggerated central hemodynamic responses characterized by an increase in stroke volume and a sustained HR response combined to yield a greater increase in CO during upright movement. This greater central response coupled with the increased PP and LVC explains the twofold greater and more sustained increase in movement-induced hyperemia in the upright compared with supine position and has clinical implications for rehabilitative medicine.     

Lung water volume at rest and exercise in dogs.

Lung water volume was measured in dogs killed at rest and during maximal exercise. There was no significant difference between them. It is concluded that pulmonary interstitial edema does not occur during exercise.     

Comparing cardiovascular responses during exercise between head-down tilt pedaling with lower body negative pressure and upright cycling in man

If lower body negative pressure (LBNP) loaded on exercise in weightlessness environment is able to derive a comparable cardiovascular responses to these in the ground, it should be identified as an optimal LBNP for exercise in space. To investigate the LBNP, 7 young subjects were exercised 4 work rates stepping up every 50 watts from 50 watts to 200 watts every 5 minutes in the upright position or 6 degree head down tilt position with each LBNP of 20, 40, 60, 80, and 100 mmHg. Oxygen uptake during tilt exercise with over 60 mmHg LBNP was not different from it in upright exercise. Heart rate and systolic arterial pressure responses to exercise were very similar between tilt exercise with 60 mmHg LBNP and upright exercise. In conclusion, the optimal LBNP loaded on exercise in space should be around 60 mmHg.     

Transcapillary fluid shifts in tissues of the head and neck during and after simulated microgravity.

To understand the mechanism, magnitude, and time course of facial puffiness that occurs in microgravity, seven male subjects were tilted 6 degrees head-down for 8 h, and all four Starling transcapillary pressures were directly measured before, during, and after tilt. Head-down tilt (HDT) caused facial edema and a significant elevation of microvascular pressures measured in the lower lip: capillary pressures increased from 27.7 +/- 1.5 mmHg (mean +/- SE) pre-HDT to 33.9 +/- 1.7 mmHg by the end of tilt. Subcutaneous and intramuscular interstitial fluid pressures in the neck also increased as a result of HDT, whereas interstitial fluid colloid osmotic pressures remained unchanged. Plasma colloid osmotic pressure dropped significantly by 4 h of HDT (21.5 +/- 1.5 mmHg pre-HDT to 18.2 +/- 1.9 mmHg), suggesting a transition from fluid filtration to absorption in capillary beds between the heart and feet during HDT. After 4 h of seated recovery from HDT, microvascular pressures in the lip (capillary and venule pressures) remained significantly elevated by 5-8 mmHg above baseline values. During HDT, urine output was 126.5 ml/h compared with 46.7 ml/h during the control baseline period. These results suggest that facial edema resulting from HDT is caused primarily by elevated capillary pressures and decreased plasma colloid osmotic pressures. The negativity of interstitial fluid pressures above heart level also has implications for maintenance of tissue fluid balance in upright posture.     

Interactive effects of body posture and exercise training on maximal oxygen uptake

To determine the effect of posture on maximal O2 uptake (VO2 max) and other cardiorespiratory adaptations to exercise training, 16 male subjects were trained using high-intensity interval and prolonged continuous cycling in either the supine or upright posture 40 min/day 4 days/wk for 8 wk and 7 male subjects served as non-training controls. VO2 max measured during upright cycling and supine cycling, respectively, increased significantly (P less than 0.05) by 16.1 +/- 3.4 and 22.9 +/- 3.4% in the supine training group (STG) and by 14.6 +/- 2.0 and 6.0 +/- 2.0% in the upright training group (UTG). The increase in VO2 max measured during supine cycling was significantly greater (P less than 0.05) in the STG than in the UTG. The increase in VO2 max in the UTG was significantly greater (P less than 0.05) when measured during upright exercise than during supine exercise. However, there was no significant difference in posture-specific VO2 max adaptations in the STG. A postural specificity was also evident in other maximal cardiorespiratory variables (ventilation, CO2 production, and respiratory exchange ratio). In the UTG, maximal heart rate decreased significantly (P less than 0.05) only during supine cycling; there was no significant difference in maximal heart rate after training in the STG. We conclude that posture affects maximal cardiorespiratory adaptations to cycle training. Additionally, supine training is more effective than upright training in increasing maximal cardiorespiratory responses measured during supine exercise, and the effects of supine training generalize to the upright posture to a greater extent than the effects of upright training generalize to the supine posture.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhanced slow caudad fluid shifts in orthostatic intolerance after 24-h bed-rest

To evaluate mechanisms of late orthostatic intolerance, slow fluid shifts along the body axis were studied during deconditioning by 24-h bed-rest and during 13-min upright tilts before and after this manoeuvre. In 11 healthy male subjects the fluid volumes of a thorax and a calf segment (impedance plethysmography) as well as tissue thickness at the forehead and the tibia (miniature ultrasonic plethysmograph) were recorded. Cardiovascular performance was monitored by recording heart rate (electrocardiogram), brachial and finger arterial pressure (by the Riva Rocci method and by the Finapres technique) as well as stroke volume (by impedance cardiography). Bed-rest led to a cephalad fluid shift with a mean interstitial leg dehydration of 2.2 ml·-100 ml^–1 with no changes in body mass and plasma volume. No syncope during the tilt occurred before bed-rest, while after bed-rest 8 subjects fainted between min 2.1 and 9.0 of the tilt. Bed-rest resulted in an augmented initial heart rate response to tilting which was similar in all subjects. In later orthostasis, bed-rest caused two- to threefold faster caudad fluid shifts with higher calf filtration rates in fainters (prior to hypotension) than in nonfainters. Through bed-rest the estimated extravasation within 10 min into general lower body tissue spaces increased by 192 ml in (late) fainters as opposed to only 23 ml in nonfainters. It was concluded that contributing factors to orthostatic intolerance may be slow transcapillary fluid shifts which are easily underestimated and whose quantity and time course call for further investigation after various deconditioning manoeuvres. In particular, the postflight fluid shifts in astronauts who will have markedly dehydrated legs, may impose a circulatory stress which needs to be evaluated. In general, the filtration rate in relevant areas appears to be an integrative and easily determined parameter, reflecting hormonal and neurogenic vascular as well as local interstitial control of the Starling forces.     

Muscle blood flow response to contraction: influence of venous pressure.

The skeletal muscle pump is thought to be at least partially responsible for the immediate muscle hyperemia seen with exercise. We hypothesized that increases in venous pressure within the muscle would enhance the effectiveness of the muscle pump and yield greater postcontraction hyperemia. In nine anesthetized beagle dogs, arterial inflow and venous outflow of a single hindlimb were measured with ultrasonic transit-time flow probes in response to 1-s tetanic contractions evoked by electrical stimulation of the sciatic nerve. Venous pressure in the hindlimb was manipulated by tilting the upright dogs to a 30 degrees angle in the head-up or head-down positions. The volume of venous blood expelled during contractions was 2.2 +/- 0.2, 1.6 +/- 0.2, and 1.4 +/- 0.2 ml with the head-up, horizontal, and head-down positions, respectively. Although altering hindlimb venous pressure influenced venous expulsion during contraction, the increase in arterial inflow was similar regardless of position. Moreover, the volume of blood expelled was a small fraction of the cumulative arterial volume after the contraction. These results suggest that the muscle pump is not a major contributor to the hyperemic response to skeletal muscle contraction.