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1 The John B. Pierce Laboratory, Department of Cellular and Molecular Physiology, and Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06519; and 2 Metabolism Unit, Shriners Burns Institute, and Departments of Surgery, Anesthesiology, and Internal Medicine, University of Texas Medical Branch at Galveston, Galveston, Texas 77550
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ABSTRACT |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Yang, Roger C., Gary W. Mack, Robert R. Wolfe, and Ethan R. Nadel. Albumin synthesis after intense intermittent exercise in
human subjects. J. Appl. Physiol.
84(2): 584-592, 1998.
We measured hepatic albumin synthesis in
five volunteers (4 men and 1 woman) at 3 and 6 h after recovery from
intense exercise. A primed-constant infusion of a stable isotopic
tracer of phenylalanine was used to determine hepatic fractional
synthetic rate (FSR) and absolute synthetic rate (ASR) of albumin from
the enrichment of phenylalanine in albumin. The infusion of the stable
isotope tracer began 2 h after upright exercise or upright rest.
Albumin FSR and ASR were 6.39 ± 0.48%/day and 120 ± 9 mg · kg body
wt
1 · day1,
respectively, 3-6 h after recovery from exercise; the FSR and ASR
on the time control study day were 5.94 ± 0.47%/day and 104 ± 9 mg · kg body
wt1 · day1,
respectively. The 6 and 16% increases
(P < 0.05) in FSR and ASR after
exercise were associated with an elevated plasma albumin content at 5 and 6 h of recovery (P < 0.05), an
increased total protein content throughout recovery
(P < 0.05), and a negative free
water clearance (P < 0.05) at 2, 3, and 6.5 h of recovery compared with baseline values; these variables
were unchanged from their baselines on the time control study day.
Increased albumin content and reduced free water clearance contribute
to a retention of fluid within the circulation after intense exercise. The measured increase in albumin synthesis could not account for the
entire increase in albumin content at 6 h of recovery from exercise.
However, we estimate that if the increased activity was maintained for
the next 18 h, it could account for the expected increase in albumin
content at 24 h of recovery.
blood volume; plasma volume; hypervolemia; stable isotopes; phenylalanine
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INTRODUCTION |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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BLOOD VOLUME (BV) expansion, due to a selective increase in plasma volume (PV), generally accompanies short-term endurance-type physical training (18, 22). This hypervolemia is essentially isotonic and occurs in the context of increased intravascular total protein (TP) content, ~85% of which is in the form of albumin (7). BV expansion additionally has been shown to occur after short-term, intense exercise (15). More recently, Gillen et al. (14) showed that a single-exposure protocol involving intense, intermittent exercise produced a 10% PV expansion after 24 h. This was accompanied by a 10% increase in plasma albumin content that occurred before, and presumably caused, the PV expansion (14).
Shifts of fluid between the intravascular and the extravascular compartments accompany alterations in the transcapillary membrane hydrostatic (or filtrative) forces and osmotic (or absorptive) forces, as described by Starling (cited in Ref. 4). Selective BV expansion could be accomplished by two possible mechanisms: 1) a net decrease in filtrative forces or 2) a net increase in absorptive forces acting across and along the capillary membranes. An elevation of albumin content after exercise would cause an expansion of the intravascular fluid compartment at the expense of the extravascular compartment through the latter mechanism because of an increase in plasma oncotic pressure (23). Furthermore, the fluid volume associated with a 10% increase in albumin content (15 g), using 18 ml of water bound per gram of albumin (26), corresponds well to the volume expansion after exercise (7, 14). These results together provide strong evidence that an increase in plasma albumin content plays a critical role in the exercise-induced expansion of BV.
Although the involvement of albumin in the development and maintenance of hypervolemia is now evident, the mechanisms that increase and maintain this extra protein in the intravascular space remain obscure. An increase in albumin synthesis could account for the increase in albumin content, although albumin synthetic rate appears to be unchanged after prolonged mild exercise (5). A decrease in albumin degradation would also lead to increased plasma levels of albumin. Relatively little is known about albumin catabolism, but albumin's fractional rate of degradation appears to be mass dependent and fairly constant under widely varying conditions (20). Finally, a net influx of albumin into the intravascular space could occur as a result of increased lymphatic return of interstitial albumin. Increased lympahtic return is stimulated directly by exercise (20) and indirectly by the increases in interstitial fluid pressure occurring in exercising muscle (28) and may contribute to increased lymphatic return of albumin. Thus it is not clear whether the reported increases in plasma albumin content that likely contribute to BV expansion are due to changes in albumin synthesis rate, the albumin degradation rate, or the distribution of albumin between the intravascular and extravascular compartments.
The objectives of the present study were to test the hypothesis directly that albumin synthesis is increased after intense exercise. We employed the same single-exposure, intense intermittent exercise protocol that has been used previously to expand BV (14) and infused a stable isotopic tracer of phenylalanine (Phe) to quantify albumin synthesis during recovery from exercise.
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MATERIALS AND METHODS |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Subjects.
Five healthy volunteers (4 men and 1 woman), mean age 23.4 ± 0.7 (SE) yr and body weight (BW) 74.2 ± 8.0 kg, participated in the
study. A complete medical history and physical examination, including
12-lead electrocardiogram, showed all subjects to be in good health.
All subjects exercised regularly, but none were endurance trained or
engaged in any aerobic training programs. Their maximal aerobic power
(
O2 max)
was determined (44.3 ± 3.0 ml · min1 · kg
BW1) using an incremental
cycle ergometer protocol and direct measurements of oxygen consumption
(model 2900, SensorMedics, Yorba Linda, CA). Informed consent was
obtained from each subject before participation in the study. The study
was approved by the Yale University School of Medicine Human
Investigation Committee.
Experimental protocol.
The study used an experimental protocol design in which each subject
served as his or her own time control. The basic protocol (Fig.
1) consisted of two 24-h experimental study
days: a resting time control (RTC) day and an exercise day. Subjects
were randomly assigned to one or the other experimental study day and
returned after 
1 wk to complete the other study day. Subjects were
asked to refrain from heavy exercise during the 2 days before
experiments.
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1 · day1
and 42 kcal · kg
BW1 · day1,
with fat constituting 35% of total calories. They were also given 15 ml/kg BW of water to consume before bedtime to standardize hydration
state before measurements the next day, because fluid status has been
shown to influence subsequent intravascular volume response to exercise
(13). While they were at the GCRC, the activity of subjects was not
restricted. On awakening on the experimental day, subjects voided and
consumed a standard low-fat, carbohydrate-rich morning meal before
being escorted to the laboratory. Once in the laboratory, subjects
voided again and then drank 10 ml/kg BW of water to ensure that they
were well hydrated. The water ingestion also produced a diuresis that
was used to assess renal function. After they consumed the water, the
subjects rested in a semirecumbent position for 1.5 h. Control blood
samples were then taken from an intravenous catheter placed during the
rest period in a forearm vein. The temperature of the test room was 24°C throughout the experiments.
On the exercise study days, subjects were asked to perform eight 4-min
bouts on an upright cycle ergometer at an intensity equal to their
respiratory compensatory thresholds. Subjects' thresholds were
84-90% O2 max
(mean 86 ± 1%). These were defined during
O2 max testing as the
level of exercise oxygen uptake above which total ventilation increased
out of proportion to carbon dioxide output (29). The 4-min intense
exercise bouts were separated by 5-min recovery periods, during which
subjects were encouraged to pedal without resistance. For the initial
four bouts, intensity level was incrementally increased up to the
target intensity, and subjects completed the last four bouts entirely
at the target intensity. On the time control study days, subjects
continued resting instead of exercising. To ensure that postural
effects were minimized in the comparison of the control vs. exercise
experimental days, subjects rested on an upright cycle ergometer for 72 min during the RTC day.
The recovery period was precisely the same for each study day.
Immediately after the exercise or upright rest periods, subjects sat in
a semirecumbent position for the entire protocol except when they rose
and walked to the bathroom (~15 steps) to provide a urine sample.
Beginning 1 h after exercise or upright rest, subjects ingested
flavored Vivonex (standard dilution 1 kcal/ml) total enteral nutrition
liquid elemental diet (Sandoz Nutrition, Minneapolis, MN) at a rate of
0.24 ml/kg BW every 10 min for 5 h. The ingestion of Vivonex maximized
the liver's anabolic ability to synthesize albumin by providing excess
free amino acids (9). A 4-h primed-constant infusion of the stable
isotope tracer 6-[13C]Phe was begun 2 h after
the exercise or upright rest. A blood sample was collected 30 min
before the infusion started to determine background enrichment.
6-[13C]Phe (Cambridge
Isotope, Andover, MA), dissolved in normal saline (sterile and pyrogen
free), was infused through an intravenous catheter placed in a forearm
vein. We used a calibrated syringe pump to maintain a constant infusion
rate of 0.05 µmol · kg
BW1 · min1
(the prime infusion was 2 µmol/kg BW over a period of 2 min). A
primed-constant infusion technique (2) was chosen to avoid the
requirements of extended infusions (up to 72 h) to achieve uniform
plasma labeling (30) and the uncertainties about labeling of the
precursor pool (11) associated with traditional constant-infusion techniques. Albumin synthetic rates were determined starting at 3 h
after upright rest or exercise, 1 h after the start of the infusion, to
allow the tracer to reach steady-state levels.
Absolute PV was determined at the end of each experimental study day by
Evans blue dye dilution (16). With subjects seated in the semirecumbent
posture at 24°C, a control blood sample was collected before the
injection of 0.2 mg/kg BW Evans blue dye through an intravenous
catheter. Blood samples were taken from a different intravenous
catheter at 10, 20, and 30 min after dye injection.
Urine samples were pooled over the indicated times (Fig. 1). Subjects
were instructed to empty their bladders when voiding. Urine volume (ml)
was measured with a graduated cylinder, and an aliquot of urine was
frozen at 
20°C for later analysis of osmolality by
freezing-point depression.
Analyses.
Venous blood samples were collected without stasis through an
intravenous catheter at indicated times (Fig. 1). An aliquot of the
sample was rapidly removed for measurement in triplicate of hematocrit,
hemoglobin concentration, and TP concentration ([TP]) by
microhematocrit, cyanmethemoglobin, and refractometric techniques,
respectively. The remainder of the blood was transferred to an
Li+-heparin tube, and plasma was
obtained by centrifugation. The plasma was then stored at
20°C for later analysis of osmolality by freezing-point
depression, albumin concentration ([albumin]) by
colorimetry, and free Phe concentration ([Phe]) using an
amino acid analyzer. For samples collected at 3 and 6 h after upright rest or exercise, an additional aliquot of blood was transferred to an
Na+-citrate tube and spun by
centrifuge. The plasma obtained after centrifugation was then stored at
80°C for analysis of tracer enrichment of free plasma Phe
and albumin.
Calculations.
Reported values of absolute PV were based on Evans blue dye
concentration at the sampling time corresponding to the highest level
of blood-dye mixing. No corrections were made for the tissue uptake of
dye. Relative changes in PV (%
) were estimated on the basis of
final and initial hematocrit (%) and hemoglobin (g/dl) values
according to the following equation
![%&Dgr;PV = <FENCE><FENCE><FR><NU>Hb<SUB>i</SUB></NU><DE>Hb<SUB>f</SUB></DE></FR> × <FR><NU>[100 − Hct<SUB>f</SUB>]</NU><DE>[100 − Hct<SUB>i</SUB>]</DE></FR></FENCE> − 1</FENCE> × 100%](/content/vol84/issue2/fulltext/584/img001.gif)
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Statistics. Data were analyzed using SuperAnova statistical software (Abacus Concepts, Berkeley, CA). One-way analysis of variance with repeated measures was used to compare mean values. When significant F-ratio differences were obtained, Fisher's protected least significant difference post hoc tests were performed. Statistical significance was accepted with P < 0.05. Values are means ± SE.
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RESULTS |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Baseline. There were no significant differences between the time control and exercise experimental study days for baseline BW, PV, [albumin] and albumin content, [TP] and TP content, osmolality, and osmotic content (Table 1). The baseline plasma osmolalities for the RTC and exercise were 282 ± 2 and 284 ± 1 mosmol/kgH2O, respectively, indicating that the subjects were well hydrated on the morning of each experimental day.
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RTC and exercise. Subjects lost significantly more BW during the exercise bouts than during the RTC (0.80 ± 0.07 and 0.09 ± 0.01 kg, respectively). Compared with baseline, PV was significantly decreased by 9.7 ± 1.4 and 18.2 ± 3.7% at the end of upright rest and exercise, respectively (Fig. 3). Plasma [TP] increased significantly after upright rest and exercise, whereas [albumin] tended to increase (P = 0.13) after exercise (Table 1); TP and albumin content did not change after upright rest or exercise (Table 1, Fig. 3). Plasma osmolality was significantly elevated after exercise but was unchanged after upright rest (Table 1). In contrast, osmotic content after upright rest and exercise was significantly decreased in comparison to the respective baselines (Table 1, Fig. 3). Because of exercise-induced peripheral vascular constriction, free-flowing venous blood samples were unobtainable in two subjects during the last exercise bout. For this reason, postexercise blood data are reported as the mean of only three subjects and are not included in the statistical analysis comparing exercise with RTC (Table 1).
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Recovery. Subjects continued to lose BW during the recovery periods, losing 1.16 ± 0.12 and 0.73 ± 0.06 kg after exercise and upright rest, respectively. In contrast to the significant BW loss, PV returned to baseline by 1 h of recovery after exercise or upright rest and remained there for the entire 6-h recovery periods (Fig. 3). Albumin and TP content progressively increased during recovery from exercise, with the albumin content increase reaching statistical significance at 5 and 6 h of recovery (Fig. 3). TP content on the RTC day was significantly elevated at only 3 and 4 h of recovery, whereas albumin content was not elevated during recovery (Fig. 3). [Albumin] returned to baseline by 1 h after both exercise and upright rest and then became significantly elevated at 6 h after exercise (4.24 ± 0.22 vs. 3.97 ± 0.19 g/dl) while remaining near baseline throughout the RTC study day. [TP] returned to baseline by 2 h of recovery from exercise and continued to be near baseline for the following 4 h. [TP] on the RTC day was not significantly different from baseline during the recovery. Plasma osmolality returned to baseline by 1 h of recovery after exercise, although it was significantly higher than at 1 h after upright rest (286 ± 2 vs. 280 ± 1 mosmol/kg BW). On both study days, plasma osmotic content returned to baseline by 1 h of recovery and remained near baseline levels for the remainder of the recovery (Fig. 3). Plasma osmotic content was closely correlated with PV in all conditions.
Urine flow rate during recovery was not significantly different from baseline throughout recovery and not significantly different between the study days (Fig. 2). Osmolar clearance also was unchanged during recovery from exercise, except for the value at 3 h of recovery, which was significantly elevated compared with that at 3 h after upright rest (Fig. 2). Free water clearance was significantly decreased from baseline on the exercise study day at 2, 3, and 6.5 h after exercise (Fig. 2). Free water clearance at 3 h of recovery from exercise was also significantly lower than that at 3 h of recovery on the RTC day (Fig. 2). Free water and osmolar clearances on the RTC day were unchanged from baseline during recovery (Fig. 2).Albumin FSR and ASR.
[Phe] was unchanged from baseline during the first 3 h of
recovery from exercise or upright rest; Vivonex ingestion started at 1 h of recovery. At 3 h of recovery, [Phe] became
significantly elevated and remained so for the remainder of the
recovery during both study days (Fig. 4).
Phe content followed a course similar to [Phe], except Phe
content on the exercise day was significantly reduced during exercise
and was not significantly elevated until 4 h after exercise (Fig. 4).
There were no significant differences in [Phe] and Phe content
between the two experimental study days (Fig. 4). FSR, measured
3-6 h after upright rest and exercise, was 5.94 ± 0.47 and
6.39 ± 0.48%/day for the RTC and exercise days, respectively (Fig.
5A). The
difference between the two study days (7.7 ± 0.9%) was
significantly different from zero (Fig. 5C). ASR during the same period was
104 ± 9 and 120 ± 9 mg · kg BW1 · day1
for upright rest and exercise recoveries, respectively (Fig. 5B). The difference between the
experimental days (15.7 ± 4.5%) was statistically significant
(Fig. 5C).
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DISCUSSION |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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PV expansion leading to an increase in BV occurs with short-term endurance training (18, 22). Expanded BV appears to have a beneficial effect on the cardiovascular and thermoregulatory responses to exercise, inasmuch as heart rate is reduced for a given exercise intensity (18) and the ability to dissipate exercise-generated heat is increased (27). These are probably a consequence of the increased venous return (Starling's law of the heart) and the elevated cutaneous flow seen with hypervolemia, respectively (12). The mechanism of BV expansion likely involves induction of an increased plasma osmotic pressure, specifically via increased intravascular albumin (7, 14); however, the exact nature of the induction mechanism has not been elucidated. The significant new finding of this study is that albumin synthetic rate is increased during recovery from intense exercise, contributing to an increased intravascular albumin content and PV expansion.
RTC time control and exercise bouts. After 72 min of seated upright rest on a cycle ergometer, subjects experienced a nearly 10% decrease in PV and osmotic content, with no change in intravascular protein content. The PV decrease predicted from a 0.09-kg BW loss would be only 0.2% on the basis of total body water, assuming water is lost proportionately from all body fluid compartments. The 10% change in PV is consistent with the 8% difference in PV lost during exposure to heat between subjects in semireclining and upright seated positions (9 and 17%, respectively) (10). PV decreased by 18% during exercise, ~8% more than that due to the upright posture alone; osmotic content decreased by ~15%, but TP and albumin content were both unchanged. The constancy of TP and albumin content, along with the correlation of osmotic content with PV during RTC and exercise, confirms that an isotonic, protein-free fluid was lost preferentially from the intravascular compartment (10, 17). Movement of fluid out of the vascular space is likely due to a transient rise in capillary hydrostatic (i.e., filtration) pressure in dependent areas with changes in posture (17) and in active muscles with exercise (28), as well as an increase in intracellular osmolality with heavy exercise (28).
PV recovery. PV returned to baseline by 1 h of recovery on both experimental days, but on the exercise study day the PV recovery occurred in the presence of an ~800-ml water deficit. PV recovered in association with significantly elevated TP content; albumin content was slightly elevated, although not significantly so. TP content remained elevated throughout the recovery from exercise, and albumin content progressively increased until reaching significance by 5 and 6 h of recovery. PV recovery after cycling has been described to occur within 1-2 h (16). Our finding of elevated TP and albumin contents confirms the results of others (7, 14), except Gillen et al. (14) reported an elevation in albumin content by 1 h of recovery after a similar intense exercise protocol. The delayed increase in albumin content found in the present study is most likely related to 1) our employment of the semirecumbent recovery position (vs. upright seated), because posture is known to affect PV recovery after exercise (10), and 2) the relatively large variability in our measured [albumin] values, rendering earlier potential differences not significant.
Renal function during recovery. Free water clearance was significantly lower during recovery from exercise than before exercise. Urine flow rate and osmolar clearance were similar between baseline and recovery and between study days. These findings suggest that a concentrated urine was being produced during recovery from exercise, acting to return solute-free water to the body (4). Exercise itself is a strong stimulus for antidiuretic hormone secretion (8). Because PV and osmolality had returned to baseline by 1 h of recovery, any antidiuretic hormone-mediated water retention is directly in response to the intense exercise stimulus (3). Decreased renal blood flow could also lead to increased water reabsorption by the kidneys secondary to inadequate delivery of tubular fluid to the distal nephron; adequate delivery is required for maximal separation of solute and water (4). Exercise can reduce renal blood flow directly by modulation of sympathetic nervous activity and circulating hormones (particularly renin, angiotensin, and aldosterone) (4). Thus exercise is a potent stimulus for water retention, and an increased free water reabsorption after intense exercise may well contribute to the induction of postexercise hypervolemia.
Albumin synthesis. Plasma [Phe] and Phe content became significantly elevated with Vivonex ingestion. Preliminary experiments showed that increases in plasma Phe were well correlated with increases in the total amino acid pool. Thus an elevation in plasma Phe during the critical periods of measurement implied that hepatic synthesis of albumin was not limited by precursor amino acid availability. With hepatic anabolic ability maximized, measurement of albumin synthetic rate 3-6 h after recovery from upright rest or exercise could determine whether increased albumin synthesis (including its subsequent transport into the circulation) is responsible for the elevation in plasma albumin content during exercise-induced BV expansion. FSR and ASR during the 3- to 6-h recovery period after exercise were significantly greater by 6 and 16%, respectively, than after upright rest. The synthetic rates measured in this study are consistent with values determined by others (2, 5).
The difference in albumin synthetic rates between the two experimental days accounts for an additional 0.13 g of albumin on the exercise study day during the 3- to 6-h recovery period. However, plasma albumin content increased by 2.5 g on the exercise study day (3.3 vs. 5.8 g of additional albumin) during this same period. Clearly, plasma albumin expansion cannot be attributed to the addition of newly synthesized albumin during these 3 h of recovery. Thus the acute increase in plasma albumin content accompanying the BV expansion response to exercise is not due to an increase in hepatic albumin synthesis. Albumin degradation, although mass dependent, occurs very slowly, i.e., only ~3%/day (24). If albumin degradation were halted immediately after exercise, with no albumin degraded for the 6-h recovery period, only 0.9 g of albumin would be spared from catabolism. This amount of albumin is well below the 5.8 g of new albumin added to the circulation by 6 h of recovery from exercise, implying that a decrease in albumin catabolic rate is also unlikely to be a primary mechanism underlying the acute increase in plasma albumin content. Lymph flow is elevated during exercise and remains elevated immediately after exercise (21), resulting in a net influx of lymphatic albumin into the circulation. If lymph flow rate were maintained at this elevated rate for a period after exercise, plasma albumin content would increase accordingly. Thus albumin influx from the lymphatics is likely the immediate source of albumin that contributes to the BV expansion after intense exercise. At 6 h of recovery from exercise, intravascular albumin was 5.8 g greater than at 6 h of recovery from upright rest. This additional 5.8 g of albumin must be retained at 24 h after intense intermittent exercise in order for exercise-induced PV expansion to occur (14). To generate an additional 5.8 g of albumin by de novo synthesis, a 90% increase in the synthetic rate of albumin would have to occur over the entire 24-h period after exercise. Whereas this increase in synthetic rate is plausible (24), it would only be necessary to account for the additional intravascular albumin if none were added to the circulation from increased lymphatic flow. In contrast, if the acute increase in albumin content is mainly due to lymphatic contribution, as postulated above, a 90% increase in albumin synthetic rate for 24 h would not be necessary. This can be demonstrated by considering a model for intravascular albumin content (24) during recovery from exercise. In this model, albumin is added to the circulation through de novo synthesis by the liver and influx via the lymphatics and removed from the circulation through degradation by vascular endothelium (24) and efflux via vascular capillary leak (Fig. 6A). We measured a 16% increase in albumin ASR at 4.5 h of recovery or, when accounting for the 30-min delay between onset of albumin synthesis and hepatic secretion (23), a 16% increase in ASR over 4 h. With the assumption of a similar linear rate of increase over the 24 h, a 96% increase in ASR would occur by 24 h after exercise, accounting for the accumulation of 3.07 g of additional albumin (~32 mg/1% increase in ASR). Lymphatic flow in this model is assumed to return to preexercise levels by 6 h after exercise, such that the net influx of lymphatic albumin is zero. Albumin degradation rate is 3%/day or 0.125%/h (24), whereas albumin leaks from the vascular pool at ~4%/h (24).
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1],
D is albumin degradation from
t1 to
t2 or
0.125% · Alb(t1) · 100%1, S is de novo
hepatic synthesis of albumin from
t1 to
t2 or (22% + 4% · t2) · 0.0032 g · %1 · h1,
and t2 > t1 > 6 h. The 24-h time course of additional albumin content during recovery
from exercise based on this model is shown in Fig.
6B. This model predicts that the
additional albumin content will decrease initially because of albumin
capillary efflux and catabolism, but as albumin synthetic rate
increases, content will return by 24 h after exercise to nearly the
same levels measured at 6 h of recovery. This return occurs without the
need for elevated albumin influx via the lymphatics. This prediction
indicates that a progressive linear increase in albumin synthetic rate
to about double its baseline value will produce the elevation of
albumin content measured at 24 h in the hypervolemic response to
exercise. The condition of progressively increasing synthetic rate up
to twice normal over 24 h, although an assumption in this model, is in
accordance with 1) the progressive
increase in albumin synthesis observed in protein-depleted rats during
refeeding, where synthetic rate increased in an approximately linear
fashion for the first 24 h after refeeding (23), and
2) the ability of hepatic albumin output to be increased to about twice its normal rate (23).
Also shown in Fig. 6B are the
predicted time courses of the additional albumin content with the
following variations: 1) albumin synthetic rate is maintained at the 16% increase measured at 4.5 h
after exercise instead of progressively increasing for the 24 h (S = 16% · 0.0032 g · %1 · h1)
and 2) albumin catabolism is halted
and albumin synthesis is not increased during recovery from exercise
relative to recovery from upright rest {D = 0.125% · [130 g + Alb(t1)] · 100%1,
where 130 g is the plasma albumin content at 6 h of recovery from
exercise and [130 g + Alb(t1)]
represents the total intravascular albumin content at
t1; S = 0}. In variation 1, it is clear
that albumin synthesis must continue to rise in order for the
additional albumin gained immediately after exercise to be retained in
the circulation at 24 h of recovery. Otherwise, as this scenario shows, the additional albumin content is reduced by 24 h to one-half its level
at 6 h of recovery because of large losses to capillary leak and
catabolism. Variation 2 shows that
although the decrease is slow, the additional albumin content
nevertheless falls if only albumin catabolism is ceased in an attempt
to maintain the additional albumin in the circulation. Therefore, a
decrease in albumin catabolism (or halting catabolism entirely) alone
cannot produce the elevation in albumin content measured at 24 h of
recovery, because the capillary leak of albumin from the vascular
compartment over that period is greater than the albumin degraded.
However, this model cannot rule out a contribution of decreased
degradation to the increased albumin content at 24 h.
To determine conclusively whether albumin synthesis can singly account
for the exercise-induced hypervolemia, hepatic synthetic rates of
albumin will need to be measured at various later stages during
recovery from intense exercise. Additionally, although lymph flow is
unlikely to be elevated at 24 h after exercise, measurements of the
distribution of albumin will be critical to assess lymphatic albumin as
a source for the elevated albumin at 24 h. In humans, lymph can be
continuously sampled using peripheral lymphatic cannulation; this
technique enables collection of adequate lymph for kinetic and
physiological analyses during steady and dynamic states (6).
In summary, we measured an increase in hepatic albumin synthetic rate
3-6 h after a single exposure of intense intermittent exercise
using stable isotope methodology. This increase, although significant,
was not great enough to account for the elevation of albumin content
during the acute recovery from exercise. Via modeling, we were able to
show that this elevation in albumin synthetic rate could produce the
increased albumin expected at 24 h of recovery from exercise if the
albumin synthetic rate increased progressively by 4%/h over the 24-h
recovery period. Our model also showed that a decrease in albumin
catabolism rate could not alone account for the increase in albumin and
that albumin influx from lymphatic flow is not necessary at 24 h of
recovery. The importance of these three mechanisms in the development
and maintenance of elevated albumin content could be better defined by
measuring albumin synthesis and albumin distribution during the entire
BV expansion process.
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ACKNOWLEDGEMENTS |
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We thank the subjects for their participation, Y.-P. Chen and D. Doyle, Jr., for technical assistance in tracer analysis, C. Kokoszka and T. Morocco for technical assistance in blood and urine analyses, and S. Kavouras and A. Stahl for help during experiments.
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FOOTNOTES |
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This investigation was supported by National Heart, Lung, and Blood Institute Grant HL-20634.
Address for reprint requests: E. R. Nadel, The John B. Pierce Laboratory, 290 Congress Ave., New Haven, CT 06519.
Received 16 June 1997; accepted in final form 1 October 1997.
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REFERENCES |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Significantly
different from RTC study day, P < 0.05.
