Vol. 276, Issue 5, R1258-R1264, May 1999
Effects of acute physical exercise on hepatocyte volume and
function in rat
Martin G.
Latour,
Antoine
Brault,
Pierre-Michel
Huet, and
Jean-Marc
Lavoie
Département de Kinésiologie, Université de
Montréal and Research Centre of the Centre Hospitalier de
l'Université de Montréal, Montreal, Quebec, Canada H3C 3J7
 |
ABSTRACT |
The goal of the present experiment was to
measure the volume of the different compartments in liver of exercised
rats and to get some insights into the appropriate working of the
hepatic function following exercise. Hence, livers from male rats were isolated and perfused after treadmill exercise or rest. This procedure was performed on rats that were overnight semifasted (50% food restriction) or well fed. To evaluate the hepatocyte cell volume, the
multiple-indicator dilution curve technique was used after 40 min of
perfusion. Radioactive tracers for red blood cells, sucrose, and water
were used to measure liver vascular space, liver interstitial space,
and water cellular space, respectively. The hepatocyte function was
assessed by taurocholate and propanolol clearance. Oxygen consumption,
intrahepatic resistance, bile secretion, and lactate dehydrogenase
release estimated liver viability. Liver viability and hepatocyte
function were not changed following exercise either in the fed or in
the semifasted animals. As expected, liver glycogen levels were
significantly (P < 0.01) reduced in
the food-restricted rats. Consequently, liver glycogen levels following
exercise were decreased significantly
(P < 0.01) only in the fed rats.
Despite this, exercise decreased the hepatocyte water space in both
food-restricted and fed groups (~15%;
P < 0.01) without altering the
sinusoidal and interstitial space. The present data show that acute
exercise decreased the hepatocyte volume and that this volume change is not entirely linked to a decrease in hepatic glycogen level.
cell volume; liver viability; liver perfusion; hepatic clearance
| |
INTRODUCTION |
OVER THE LAST FEW YEARS, evidence has been gathered
that shows that the liver may act as an afferent organ contributing to the metabolic and hormonal regulation of exercise (3, 21). The best
evidence in favor of such a role by the liver during exercise comes
from the demonstration that a selective hepatic vagotomy attenuates the
exercise-induced pancreatic and norepinephrine responses in rats (21).
However, the signal and the mechanism at the origin of this hepatic
afferent information are still not fully understood. It has been
suggested that substrates such as pyruvate have a hyperpolarizing
effect on liver cells (7) and that the membrane potential of the
hepatocytes determines the firing rate of afferent neurons (29).
The interest in studying hepatocyte cell volume changes during exercise
stems from the recent reports that hepatic metabolism, not primarily
serving cell volume regulation, appears to be regulated by a new
parameter, i.e., cell volume (16, 17). It has been shown in isolated
cell studies that pancreatic hormones such as insulin and glucagon can
independently induce hepatocytes to swell or shrink, respectively (16).
Physical exercise is a situation where the pancreatic hormone response
is characterized by an increase in glucagon and a decrease in insulin.
Both of these hormone responses would stimulate a shrinkage of the
hepatocytes. It is possible that variations in hepatic cell volume
could influence hepatic metabolism during exercise. It is also possible
that a change in hepatic cell volume constitutes a signal at the origin
of the hepatic afferent information transmitted through the hepatic
vagus nerve. Supporting this view is the report that cell swelling
hyperpolarizes the cell membrane (18). With this theory in mind, a
first step toward the understanding of potential metabolic effects from
changing in hepatocyte volume was to determine whether cell volume
underwent changes subsequent to exercise. In addition, the relation
between changes in hepatocyte volume and the reduction of liver
glycogen stores during exercise was looked on by conducting the same
experiments in both normally fed and semifasted animals. Because no in
vivo models were available to directly measure the volume of the
different liver compartments in exercising rats, we used an isolated
perfused rat liver model and the multiple-indicator dilution curve
technique described by Goresky (12) to achieve this first goal.
A second objective was to document the hepatic function in a perfused
liver after an acute exercise. Some authors have reported an altered
liver function in strenuous exercise in man (1, 9). A reduced
extraction of propanolol (Pro) (1), increased liver injury (26), and
the release of liver-specific enzymes (9) were observed. Some concerns
have been, however, expressed relative to the inaccuracy of in vivo
liver extraction of some compounds during exhaustive exercise due to
caval reflux and catheter displacement in the hepatic vein occurring
during high ventilation (2, 28). In the present study, we used a rat
liver perfusion model to evaluate the effects of moderate-intensity
exercise on hepatic function immediately after exercise.
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METHODS |
Animal care. Male Sprague-Dawley rats
(Charles River, St. Constant, PQ) weighing 200-225 g were housed
in individual cages and allowed pellet rat chow and tap water ad
libitum for 15 days after they were received in our laboratory. Lights
were on from 07:00 AM until 07:00 PM, and the room temperature was
maintained at 20°C. Three days after their arrival, all rats
underwent a habituation running protocol on a motor-driven rodent
treadmill consisting of six sessions over 2 wk, beginning with 20 min/day at 15 m/min and progressively increasing in both speed and
duration to 45 min/day at 30 m/min (0% grade), so that they were well
accustomed to running and being handled. The experiments described in
this report were conducted according to the directives of the Canadian Council on Animal Care.
Groups and exercise protocol. The
night before experimentation, all rats were weighed and randomly
assigned to either well-fed or semifasted groups. Semifasted rats
received ~50% of their daily food intake (~ 11 g). On the day of
the experiment, rats were again weighed and randomly divided into a
rest and an exercise group. The experiments were run between 10:30 AM
and 01:30 PM. The exercise test consisted of running on the treadmill
at speeds and durations that totaled ~1,500 m (0% grade). The speeds
and durations used were as follows: 5 min at 15 m/min, 5 min at 20 m/min, 40 min at 26 m/min, and 10 min at 28 m/min. Rested rats were
killed at similar times as exercised rats. At the end of running or
resting conditions, all rats were rapidly anesthetized with
pentobarbital sodium (50 mg/kg ip). After complete anesthesia, the
abdominal cavity was opened and the isolation of all vessels of the
liver was rapidly started without closure of the blood circulation.
Before the beginning of the perfusion, peripheral blood (~3 ml) was
collected via the abdominal vena cava. After closure of the blood
vessels and the cannulation of the bile duct, the portal vein was
cannulated and the liver flushed with oxygenated Krebs-Henseleit
buffer. Then the whole triangular lobe of the liver was cut, weighed,
and then frozen. At the end of the 40-min perfusion, liver was flushed
again with oxygenated Krebs-Henseleit buffer and the caudate lobe of
the liver was taken, weighed, and then frozen. Pre- and postperfusion
liver tissues were used to determine glycogen concentrations. This was
done to verify whether the perfusion medium could affect glycogen content.
Isolated perfused rat liver. The liver
was perfused for 40 min through the portal vein in a closed circuit
using a perfusion apparatus (Mx/Ambex Two/ten; Mx International,
Aurora, CO). The perfusion medium (250 ml total volume) consisted of
Krebs-Henseleit buffer, pH 7.4, containing 20% prewashed bovine red
blood cells (RBCs) (vol/vol), 20 g/l albumin (wt/vol), and 1 g/l
dextrose (wt/vol). The perfusate was saturated by equilibration with
95% O2-5%
CO2, and the temperature was kept
at 37°C. Liver temperature was also kept at 37°C using a
heating lamp. The perfusion flow was measured volumetrically and fixed
at 20 ml/min (~7
ml · min
1 · 100 g body wt1 for all groups).
The measurements of taurocholate (TC) and Pro clearance assessed the
hepatocyte cell function. Throughout each perfusion period, a loading
dose of unlabeled TC and Pro (mixed with tracer doses of
[14C]TC and
[3H]Pro) was added to
the reservoir to attain theoretical plasma concentrations of 11.5 ng/ml
and 100 ng/ml of TC and Pro, respectively, followed by a continuous
infusion to maintain these levels. Viability of the perfused liver was
first assessed subjectively on the basis of gross appearance and,
thereafter, objectively on the basis of lactate dehydrogenase (LDH)
release, O2 consumption, bile
production, and intrahepatic resistance (perfusion pressure) (4, 11).
Assessment of TC and Pro clearance.
After 20 min of equilibration, perfusate plasma samples were obtained
at several time points (20, 24, 29, 35, and 40 min).
[14C]TC and
[3H]Pro plasma levels
were determined in duplicate using a beta-counter (Beckmann, Montreal,
Canada) (30). TC and Pro elimination were measured by their hepatic
clearance (Cl) using the following formula
where
Q is the perfusate flow, E is the extraction, and
Cin and
Cout are
[14C]TC or
[3H]Pro plasma levels
at inflow and outflow, respectively. The hepatic Pro clearance and
extraction were calculated similarly as for TC.
[3H]Pro and Pro
perfusate plasma levels were measured in duplicate using a specific
high-pressure liquid chromatographic method as previously reported (8).
Multiple-indicator dilution curve. At
the end of the liver function study, the hepatic venous outflow was
diverted to avoid recirculating radioactive materials; then the
multiple-indicator dilution curves were obtained after a 0.1-ml
injection of radioactive tracer mixture consisting of the following
substances: 51Cr-labeled RBCs
(105 dpm),
99Tc-labeled albumin (2 × 105 dpm),
[14C]sucrose (2 × 105 dpm), and
[3H]water (3 × 105 dpm) in a solution of
Krebs-Henseleit buffer adjusted to a hematocrit matched to that of the
perfusate containing albumin (20 g/l). The total hepatic venous outflow
was collected in serial tubes at the rate of 1 tube/s for 90 s. An
aliquot from each tube was used for the determination of gamma- and
beta-activity and processed as previously described (31). The
background contamination by [14C]TC and
[3H]Pro contained in
the perfusate was quantitatively negligible compared with the levels of
[14C]sucrose and
[3H]H2O,
respectively (<0.01% of the peak value of labeled sucrose and water
curves). Outflow activity (disintegrations per minute per milliliter)
was divided by the total amount injected (disintegrations per minute)
to yield a normalized outflow fraction per milliliter of blood, thus
providing the basis for comparison of each tracer.
The dilution curves were corrected for catheter distortion and delay as
previously described by Goresky and Silverman (14). To calculate the
sinusoidal volume, data were analyzed according to Goresky et al.'s
flow-limited model (12). This model states that the labeled RBCs
delineate the vascular space, whereas the interstitial space indicator
(high-molecular weight or labeled albumin, and low-molecular weight or
labeled sucrose), as well as the whole organ tracer (labeled water),
undergo flow-limited distribution from the sinusoidal into the Disse's
space and hepatic cellular space, respectively, in a manner
characterized by a delayed wave type of behavior. Therefore, the
dilution curve of each diffusible substance can be superimposed on that
of the RBCs if every point is corrected by a constant factor to its
corresponding point on the RBC curve using the following equation
in
which CRBC and
Cdif are the concentration values
for RBC and diffusible substance at corresponding arbitrary points in time of t(RBC) and
t'(dif), respectively;
to is the large
vessel transit time delay, and y is the ratio of extravascular to
vascular volume of distribution of diffusible substance. The values of to and y were
determined as those yielding the least sum of square of deviations
between the RBC curves and the diffusible substance curves when the
latter is transformed linearly to be superimposed on the first. The
optimization procedure was guided by a least-square minimization
algorithm programmed in Turbo Pascal and Lotus 123 on a Hewlett-Packard
computer (Vectra 286 series, Palo Alto, CA). Results of the nonlinear
fitting procedure were examined by visual inspection of the fitting
curve (25) and by measuring the coefficients of variation (13) and
determination (10) of the fit. Once the y and
to were obtained,
the vascular (sinusoidal) volume
(Vsin) was calculated as
in
which tRBC is the
corrected mean transit time of RBC calculated according to Meier and
Zierler (24). Extravascular volume (EV) accessible to albumin and
sucrose (EVSuc) was calculated as a model-independent parameter according to the transit time method
of Chinard et al. (5) as
where
tdif is the
corrected mean transit time of diffusible substances (albumin and
sucrose). Extravascular water space was calculated using the same
formula with the exception that, in that case, Q equals water flow
(Qw), which must be previously calculated as
in
which 0.7 and 0.93 represent the proportion of water (ml/ml) in RBC and
plasma, respectively (6). The hepatic cellular water space
(Vcell) is consequently
Analytic methods. Peripheral blood was
collected (<1.5 min) into three 1-ml syringes with 15% EDTA and
immediately separated into two fractions. One fraction of blood (500 µl) was preserved in 50 µl Trasylol and centrifuged at 4°C, and
the plasma was used for glucagon determination. The remainder of the
blood was also centrifuged (Eppendorf centrifuge, no. 5415), and the
plasma was stored (
70°C) for subsequent glucose, insulin,
and free fatty acids (FFA) determinations.
Plasma glucose concentrations were determined by the use of a glucose
analyzer (Yellow Springs Instruments 2300, Yellow Springs, OH). Insulin
and glucagon concentrations were determined by commercially available
radioimmunoassay kits (Radioassay System Laboratory; ICN Biomedicals,
Costa Mesa, CA; distributed by Immunocorp, Montreal, Quebec). Free
fatty acids were assessed enzymatically with the use of reagent kits
from Boehringer Mannheim Laboratories (distributed by Immunocorp). The
liver was precisely weighed with an electronic balance (Mettler AE
100). Liver glycogen concentration was determined by use of the
phenol-sulfuric acid reaction (23). The nonperfused areas were finally
assessed histologically by the use of Trypan blue (200 mg%
Krebs-Henseleit buffer, Aldrich 30, 264-3). All data are reported
as means ± SE. Statistical analyses were performed using a two-way
analysis of variance with exercise and dietary state as factors.
Scheffé's post hoc test was used in the case of a significant
(P < 0.05)
F ratio.
| |
RESULTS |
As expected, the mean body weights of the semifasted rats were
significantly (P < 0.01) lower than
those of the fed rats (Table 1). There was,
however, no difference in body weights between the exercised and the
rested groups in both fed and semifasted groups. Because the
liver-to-body weight ratio was significantly (P < 0.01) decreased with exercise,
whereas the rat body weight remained unchanged (Table 1), it was
decided to express all parameters related to hepatic measurements per
one hundred grams of body weight instead of per gram of liver weight.
Food restriction (one-half fast) the night before experimentation
resulted in significantly (P < 0.01)
lower levels of liver glycogen, plasma glucose, and insulin
concentrations (Fig. 1, A, B,
and D). As expected, exercise
resulted in a significant (P < 0.05)
decrease in plasma glucose, insulin, and liver glycogen levels in the
fed state while significantly (P < 0.05) increasing glucagon and plasma FFA concentrations (the latter in
semifasted rats only; Fig. 1, C and
D). A small but significant
(P < 0.05) difference in liver
glycogen in pre- vs. postinfusion period was found only in the
postexercise fed situation (Fig.
1A).
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Fig. 1.
Liver glycogen (pre- and postperfusion), peripheral plasma glucose,
free fatty acids, insulin, and glucagon concentrations at rest and
postexercise. Values are means ± SE;
n = 5 or 6 and 6-8 rats at each
point in fed and semifasted groups, respectively. * Significantly
different from corresponding resting values,
P < 0.05. + Significant difference at
P < 0.001 between semifasted and fed
state. § Significant difference at
P < 0.05 between preperfusion and
postperfusion.
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Liver viability parameters such as hepatic oxygen consumption, bile
secretion, intrahepatic resistance, and LDH release, measured between
the 20th and 40th min of the perfusion, were within normal values in
all groups and were not significantly
(P > 0.05) affected by fasting or
exercise (Fig. 2). The only exception to
these observations was the LDH release, which was found to be
significantly (P < 0.01) more
elevated in semifasted than in fed rats (Fig.
2D). Pro and TC hepatic clearance
was not significantly (P > 0.05) changed with exercise either in fed or semifasted rats (Fig.
3). However, the intracellular water space
of hepatocytes was significantly (P < 0.01) decreased following exercise (~15%; Fig.
4A). The
exercise-stimulated decrease in liver cell volume was observed in fed
as well as in semifasted rats, even though in the latter, cell volume
was significantly (P < 0.01) lower
than in the former. Sinusoidal space as well as albumin and sucrose
interstitial spaces were not significantly (P > 0.05) changed in all
experimental conditions.
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Fig. 2.
Liver O2 consumption, bile
secretion, intrahepatic resistance, and lactate dehydrogenase (LDH)
release at rest and postexercise. Values are means ± SE;
n = 5 or 6 and 6-8 rats at each
point in fed and semifasted groups, respectively. BW, body wt. + Significant difference at P < 0.005 between semi-fasted and fed state.
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Fig. 3.
Liver taurocholate (TC) and propanolol (Pro) clearance at rest and
postexercise. Values are means ± SE;
n = 5 or 6 and 6-8 rats at each
point in fed and semifasted groups, respectively.
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Fig. 4.
Hepatocyte cellular water space, sinusoidal space, and sucrose and
albumin interstitial spaces at rest and postexercise. Values are means ± SE; n = 5 or 6 and 6-8 rats
at each point in fed and semifasted groups, respectively.
* Significantly different from corresponding resting values,
P < 0.005. + Significantly
different at P < 0.005 between
semifasted and fed state.
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| |
DISCUSSION |
The present experiment was designed to ascertain the decrease of liver
cell volume induced by a 60-min exercise bout of moderate intensity.
The present data are the first to our knowledge to confirm the
hypothesis of an exercise-induced hepatic cell shrinkage. The
hypothesis that physical exercise could potentially reduce the
intracellular water content of liver has previously been made (22).
Lehmann et al. (22) suggested that the average 7.6% plasma volume
increase with a mean 3.3-kg body mass decrease following an
ultratriathlon (23 h) in man was due to multiple factors, such as the
decrease in intracellular water of muscles and liver. Other researchers
have reported an exercise-induced 21% loss of hepatic water using
gravimetric measurements (20). In the present report, we show an
exercise-induced 15% decrease of the hepatocellular hydration level
using a specific and reliable technique in isolated perfused rat liver.
With this method we can confirm a selective hepatocyte water loss
during exercise without any significant changes in interstitial and
sinusoidal spaces.
As expected, the 60-min exercise period resulted in a decrease in blood
glucose and insulin and in an increase in glucagon concentrations in
all groups. Because liver glycogen levels were already decreased in
semifasted rats, liver glycogen concentrations were decreased
significantly only in the fed rats following exercise. Consequently,
the amount of liver glycogen used during exercise was ~15 times
higher in the fed than in the semifasted animals. Interestingly, the
different amount of liver glycogen used during exercise did not lead to
a different decrease in hepatocellular volume, the reduction being
~15% in both groups. This observation suggests that the reduction in
hepatocyte volume following exercise is not entirely due to the loss in
glycogen and to the water that is associated with it (27). In search of
an alternative explanation for the exercise-induced decrease in liver
cell volume, one has to consider the decrease in insulin and the
increase in glucagon levels during exercise. In perfused liver,
insulin, by acting on different transport systems, leads to cellular
accumulation of K+,
Na+, and
Cl and, consequently, to
cell swelling (16, 19). Glucagon, on the other hand, is known to
decrease cellular K+ in isolated
perfused rat liver, resulting in cell shrinkage (15). During exercise,
with insulin concentration decreasing and glucagon concentration
increasing, both of these stimuli should lead to a shrinkage of liver
cells. It is therefore possible that the typical pancreatic hormone
response to exercise, by acting on different transport systems in the
liver, leads to cell shrinkage. Overall, the present results indicate
that the present 15% decrease in hepatocyte water space following
exercise cannot solely be attributed to a loss of glycogen. This
observation suggests that liver cell shrinkage during exercise is
induced by specific mechanisms and is not only a consequence of an
increased glycogen breakdown.
The physiological relevance of the liver cell shrinkage during exercise
could be related to specific hepatic functions or to a hepatic afferent
contribution to the overall metabolism. After 60 min of exercise,
Kasperek et al. (20) reported an increased osmotic fragility in liver
cell lysosomes, which was associated with the exercise increase in the
rate of protein degradation via the autophagolysosomal system. These
authors (20) mention that, although the signal that causes autophagy is
not known with certainty, the typical hormonal status of exercise could
induce autophagy. It is interesting to relate these speculations with the concept put forward by Lehmann et al. (22) that a protein-catabolic signal might be triggered by a decrease in cellular hydration of liver
cells at the background of the particular hormonal pattern during
prolonged exercise. A decrease in hepatocellular hydration state has
also been reported to stimulate glycogenolysis (17), which would be
particularly relevant to exercise energy metabolism. Whether the
variation of cellular volume of hepatocyte could represent an afferent
signal perceived or transmitted through hepatic nervous pathways,
contributing to hormonal and other changes that occur during exercise,
remains hypothetical. It is interesting to note, however, that cell
swelling hyperpolarizes the cell membrane (18), providing a potential
link with the activity of afferent neurons (29).
A second objective of the present study was to document how acute
physical exercise can affect liver function. The hepatic clearance of
TC and Pro were unchanged in all rats following exercise. This
observation indicates that an acute 60-min bout of exercise at moderate
intensity is not detrimental to the liver function in rats. Even though
LDH release was found to be slightly but significantly higher in
semifasted compared with fed rats, there were no effects of exercise on
LDH release either in fed or in semifasted rats. This indicates that
hepatocyte lysis was not changed by the present exercise protocol.
Other viability parameters, such as the hepatic oxygen consumption and
intrahepatic resistance, were all within normal values whether in
rested or exercised rats. Finally, the bile secretion values remained
normal throughout the perfusion in all groups and do not support the
reported reduction in bile flow or cholestasis with exhaustive exercise
in rats (32). Overall, our results indicate a normal hepatic
functionality following exercise under the present experimental conditions.
In summary, acute physical exercise in rats results in a shrinkage of
the liver cells, as assessed in situ under basal unstimulated conditions. Exercised livers displayed a ~15% decrease in the hepatocellular hydration level compared with rest condition. These results confirm the hypothesis that there is an exercise-induced hepatocyte shrinkage and show that it cannot be solely linked to a
decrease in the hepatic glycogen level. The hepatic function, as
assessed by the clearance of TC and Pro, is not altered following a
moderate exercise, which suggests an absence of postexercise hepatic
function deterioration.
Perspectives
In recent years, our laboratory has devoted a fair amount of time to
gathering data supporting the hypothetical construct that the liver,
through its afferent activity, may contribute to the metabolic and
hormonal regulation of exercise (3, 21). The nature of the metabolic
activity in the liver and the regulatory mechanism responsible for this
afferent activity remain poorly understood. In recent years, it has
been suggested that hepatic metabolism appears to be regulated by a new
parameter, i.e., cell volume (16, 17). In the liver, it seems that
alterations of cell volume markedly influence a variety of metabolic
pathway not primarily serving cell volume regulation (16). The results of the present study show that in fact liver cell volume is reduced during exercise and that this reduction is not entirely due to the loss
of glycogen. Future studies will be needed to show whether the
reduction in liver cell volume is a regulator contributing to intra-
and/or extrahepatic metabolic adaptations to exercise.
| |
ACKNOWLEDGEMENTS |
We express our appreciation to Marlène Fortier (Institut
National de la Recherche Scientifique-Santé, Point-Claire,
Quebec) and to Louise Gariépy for the propanolol extraction analysis.
| |
FOOTNOTES |
Grants from Natural Sciences and Engineering Research Council and the
Medical Research Council of Canada and Fonds pour la Formation des
Chercheurs et L'Aide à la Recherche (Government of Quebec)
supported this work.
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.-M. Lavoie,
Département de kinésiologie, Université de
Montréal, C. P. 6128, Succ. Centre-ville Montreal, Quebec, Canada
H3C 3J7 (E-mail: Jean-Marc.Lavoie{at}UMontreal.CA).
Received 13 July 1998; accepted in final form 11 January 1999.
| |
REFERENCES |
1.
Arends, B. G.,
R. O. B. Bohm,
J. E. van Kemenade,
K. H. Rahn,
and
M. A. van Baak.
Influence of physical exercise on the pharmacokinetics of propanolol.
Eur. J. Clin. Pharmacol.
31:
375-377,
1986[Medline].
2.
Brauer, R. W.
Liver circulation and function.
Physiol. Rev.
43:
115-143,
1963[Free Full Text].
3.
Cardin, S.,
R. Helie,
R. Bergeron,
B. Comte,
G. van de Werve,
and
J.-M. Lavoie.
Effect of hepatic portal infusion of pyruvate on pancreatic hormone response during exercise.
Am. J. Physiol.
266 (Regulatory Integrative Comp. Physiol. 35):
R1630-R1636,
1994[Abstract/Free Full Text].
4.
Cheung, K.,
P. E. Hickman,
J. M. Potter,
N. I. Walker,
M. Jericho,
R. Haslam,
and
M. S. Roberts.
An optimized model for rat liver perfusion studies.
J. Surg. Res.
66:
81-89,
1996[Medline].
5.
Chinard, F. P.,
T. Enns,
and
M. F. Nolan.
Pulmonary extravascular water volumes from the transit-time and slope data.
J. Appl. Physiol.
17:
179-183,
1962[Abstract/Free Full Text].
6.
Cousineau, D.,
C. A. Goresky,
and
C. Rose.
Reflex sympathetic effects on liver vascular space and liver perfusion in dogs.
Am. J. Physiol.
248 (Heart Circ. Physiol. 17):
H186-H192,
1985.
7.
Dambach, G.,
and
N. Friedmann.
Substrate-induced membrane potential changes in the perfused rat liver.
Biochim. Biophys. Acta
367:
366-370,
1974[Medline].
8.
Fenyves, D.,
L. Gariepy,
and
J. P. Villeneuve.
Clearance by the liver in cirrhosis. I. Relationship between propranolol metabolism in vitro and its extraction by the perfused liver in the rat.
Hepatology
17:
291-296,
1993.
9.
Fojt, E.,
L.-G. Ekelund,
and
E. Hultman.
Enzyme activities in hepatic venous blood under strenuous physical exercise.
Pflügers Arch.
361:
287-296,
1976[Medline].
10.
Forker, E. L.,
and
B. A. Luxon.
Hepatic transport kinetics and plasma disappearance curves: distribution modeling versus conventional approach.
Am. J. Physiol.
235 (Endocrinol. Metab. Gastrointest. Physiol. 6):
E648-E660,
1978.
11.
Gores, G. J.,
L. J. Kost,
and
N. F. LaRusso.
The isolated perfused rat liver: conceptual and practical considerations.
Hepatology
6:
511-517,
1986[Medline].
12.
Goresky, C. A.
A linear method for determining liver sinusoidal and extravascular volume.
Am. J. Physiol.
204:
626-640,
1963.
13.
Goresky, C. A.,
G. G. Bach,
and
B. E. Nadeau.
On the uptake of material by the intact liver. The transport and the net removal of galactose.
J. Clin. Invest.
52:
991-1008,
1973.
14.
Goresky, C. A.,
and
M. Silverman.
Effect of the correction of the catheter distortion on calculated liver sinusoidal volumes.
Am. J. Physiol.
207:
883-892,
1964.
15.
Hallbrucker, C.,
S. vom Dahl,
F. Lang,
W. Gerok,
and
D. Haussinger.
Modification of liver cell volume by insulin and glucagon.
Pflügers Arch.
418:
519-521,
1991[Medline].
16.
Haussinger, D.,
and
F. Lang.
Cell volume in the regulation of hepatic function: a mechanism for metabolic control.
Biochim. Biophys. Acta
1071:
331-350,
1991[Medline].
17.
Haussinger, D.,
F. Lang,
and
W. Gerok.
Regulation of cell function by the cellular hydration state.
Am. J. Physiol.
267 (Endocrinol. Metab. 30):
E343-E355,
1994[Abstract/Free Full Text].
18.
Howard, L. D.,
and
R. Wondergem.
Effects of anisosmotic sodium on cell volume, transmembrane potential and intracellular K+ activity in mouse hepatocytes.
J. Membr. Biol.
100:
53-61,
1987[Medline].
19.
Jakubowski, J.,
and
A. Jacob.
Vasopressin, insulin and peroxide(s) of vanadate (pervanadate) influence Na+ transport mediated by (Na+/K+)ATPase or Na+/H+ exchanger of rat liver plasma membrane vesicles.
Eur. J. Biochem.
193:
541-549,
1990[Medline].
20.
Kasperek, G. J.,
G. L. Dohm,
H. A. Barakat,
P. H. Strausbauch,
D. W. Barnes,
and
R. D. Snider.
The role of lysosomes in exercise-induced hepatic protein loss.
Biochem. J.
202:
281-288,
1982[Medline].
21.
Lavoie, J.-M.,
S. Cardin,
and
B. Doiron.
Influence of hepatic vagus nerve on pancreatic hormone secretion during exercise.
Am. J. Physiol.
257 (Endocrinol. Metab. 20):
E855-E859,
1989[Abstract/Free Full Text].
22.
Lehmann, M.,
M. Huonker,
F. Dimeo,
N. Heinz,
U. Gastrmann,
N. Treis,
J. M. Steinacker,
J. Keul,
R. Kajewsky,
and
D. Haussinger.
Serum amino acids concentrations in nine athletes before and after the 1993 Colmar Ultra Triathlon.
Int. J. Sports Med.
16:
155-159,
1995[Medline].
23.
Lo, S.,
C. Russell,
and
A. W. Taylor.
Determination of glycogen in small tissue samples.
J. Appl. Physiol.
28:
234-236,
1970[Free Full Text].
24.
Meier, P.,
and
K. L. Zierler.
On the theory of the indicator-dilution method for the measurement of blood flow and volume.
J. Appl. Physiol.
6:
731-744,
1954[Free Full Text].
25.
Motulsky, H. J.,
and
L. A. Ransas.
Fitting curves to data using nonlinear regression.
FASEB J.
1:
365-374,
1987[Abstract].
26.
Nagel, D.,
D. Seiler,
H. Franz,
and
K. Jung.
Ultra-long-distance running and the liver.
Int. J. Sports Med.
11:
441-445,
1990[Medline].
27.
Olsson, K.-E.,
and
B. Saltin.
Variation in total body water with muscle glycogen changes in man.
Acta Physiol. Scand.
80:
11-18,
1970[Medline].
28.
Rowell, L. B.,
J. R. Blackmon,
and
R. A. Bruce.
Indocyanine green clearance and estimated hepatic blood flow during mild to maximal exercise in upright man.
J. Clin. Invest.
43:
1677-1690,
1964.
29.
Russek, M.
Current status of the hepatostatic theory of food intake control.
Appetite
2:
137-143,
1981[Medline].
30.
Sutto, F.,
A. Brault,
R. Lepage,
and
P. M. Huet.
Metabolism of hyaluronic acid by liver endothelial cells: effect of ischemia-reperfusion in the isolated perfused rat liver.
J. Hepatol.
20:
611-616,
1994[Medline].
31.
Varin, F.,
and
P. M. Huet.
Hepatic microcirculation in the perfused cirrhotic rat liver.
J. Clin. Invest.
76:
1904-1912,
1985.
32.
Villa, J. G.,
M. M. Almar,
P. S. Collado,
E. Llamazares,
and
J. Gonzales-Gallego.
Impairment of bile secretion induced by exhaustive exercise in the rat.
Int. J. Sports Med.
14:
179-184,
1993[Medline].
Am J Physiol Regul Integr Compar Physiol 276(5):R1258-R1264
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ABSTRACT
INTRODUCTION
![Q<SUB>W</SUB> = (Q × hematocrit × 0.7) + [Q × (1 − hematocrit) × 0.93]](/content/vol276/issue5/fulltext/R1258/img005.gif)
