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Copenhagen Muscle Research Centre, Rigshospitalet, DK-2200 Copenhagen N, Denmark
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ABSTRACT |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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The present study compared the microdialysis ethanol
outflow-inflow technique for estimating blood flow (BF) in skeletal
muscle of humans with measurements by Doppler ultrasound of femoral
artery inflow to the limb
(BFFA). The microdialysis probes
were inserted in the vastus lateralis muscle and perfused with a Ringer
acetate solution containing ethanol,
[2-3H]adenosine (Ado),
and
D-[14C(U)]glucose.
BFFA at rest increased from
0.16 ± 0.02 to 1.80 ± 0.26 and 4.86 ± 0.53 l/min
with femoral artery infusion of Ado (AdoFA,i) at 125 and 1,000 µg · min
1 · l1
thigh volume (low dose and high dose, respectively;
P < 0.05) and to 3.79 ± 0.37 and
6.13 ± 0.65 l/min during one-legged, dynamic, thigh muscle exercise
without and with high AdoFA,i,
respectively (P < 0.05). The ethanol
outflow-to-inflow ratio (38.3 ± 2.3%) and the probe recoveries
(PR) for [2-3H]Ado
(35.4 ± 1.6%) and for
D-[14C(U)]glucose
(15.9 ± 1.1%) did not change with
AdoFA,i at rest (P = not significant). During exercise
without and with AdoFA,i, the
ethanol outflow-to-inflow ratio decreased
(P < 0.05) to a similar level of
17.5 ± 3.4 and 20.6 ± 3.2%, respectively
(P = not significant), respectively,
while the PR increased (P < 0.05) to
a similar level (P = not significant)
of 55.8 ± 2.8 and 61.2 ± 2.5% for
[2-3H]Ado and to 42.8 ± 3.9 and 45.2 ± 5.1% for
D-[14C(U)]glucose.
Whereas the ethanol outflow-to-inflow ratio and PR correlated inversely
and positively, respectively, to the changes in BF during muscular
contractions, neither of the ratio nor PR correlated to
the AdoFA,i-induced BF increase.
Thus the ethanol outflow-to-inflow ratio does not represent skeletal
muscle BF but rather contraction-induced changes in molecular transport in the interstitium or over the microdialysis membrane.
adenosine; exercise; heterogeneity; hyperemia ; glucose
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INTRODUCTION |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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SKELETAL MUSCLE BLOOD FLOW (BF) increases rapidly at onset of voluntary contractions (24) to make the delivery of nutrients meet the elevated metabolic demands. The elevation in BF is linearly related to the work intensity (3, 23, 25) and may, at peak power output, exceed the basal resting level by a factor of 50 (27). Recently, the microdialysis technique was applied to study interstitially local metabolism in skeletal muscle of humans (26). By adding ethanol to the microdialysis infusate, i.e., a tracer suggested to be metabolically inert in the muscle, changes in local muscle BF were proposed to be represented by the microdialysis ethanol concentration ([ethanol]) outflow-to-inflow ratio ([ethanol]dialysate/[ethanol]infusate) (10). This method has subsequently been used in attempts to estimate changes in local BF in skeletal muscle of animals and humans (9-11, 26). A mathematical model has also been derived for quantification of muscle BF from the microdialysis probes (31).
In the investigation of the distribution of BF within skeletal muscle of animals, a marked spatial and temporal heterogeneity has been found by using radioactive labeled microspheres (13, 14, 19, 21, 22). This finding may indicate regional differences in the circulatory regulation related to the local metabolic demand, or an intermittent regional perfusion not to exceed the total inflow capacity, or minimize persistent local hypoperfusion and thus regional fatigue. However, it also implies that any type of extrapolation of total muscle BF from a few microdialysis probes may be misleading. Moreover, knowledge of the local BF distribution within skeletal muscle of humans is still limited. Thus, although it would be erroneous to estimate total muscle BF with the ethanol-dialysis technique from a few microdialysis probes in skeletal muscle of humans, the technique could still though be a unique tool to measure variations in the BF distribution and its temporal and spatial relationship to the local interstitial release of metabolites and other vasodilators.
However, when the ethanol-removal technique was established (8-10), in one study it was specifically validated against 133Xe clearance (8), which is known to show a nonlinear response and to have inherent methodological limitations, such as differences in tissue tracer solubility, therefore underestimating true muscle BF (5-7, 18, 29, 30). Furthermore, it was not thoroughly investigated whether the changes in ethanol removal during muscular contractions purely represented changes in muscle BF or whether changes in ethanol removal could reflect the effect of other factors causing alterations in the molecular transport across the micodialysis membrane. The latter question may now be investigated by determining the relative loss [probe recovery (PR)] of radioactive-labeled molecules across the microdialysis membrane (15, 17, 28). Moreover, a nonlinearity in the changes of ethanol outflow-to-inflow ratio has also been found during incremental exercise (9); in contrast, the muscle BF is known to increase linearly with increasing intensity (3, 23, 25).
Therefore the purpose of the present study was to investigate the validity of the microdialysis ethanol-removal technique for estimating changes in skeletal muscle BF in humans. To uncouple the effects on the ethanol removal induced by BF vs. muscle mechanical factors, limb BF was measured at rest and during passive as well as voluntary one-legged, dynamic, thigh muscle exercise, with and without infusion of the vasodilator adenosine (Ado) in the femoral artery.
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MATERIALS AND METHODS |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Subjects. Fourteen healthy men [age, 24.6 ± 0.7 (SE) yr (range, 21-32 yr); height, 183.2 ± 1.6 cm (range, 172-190 cm); and weight, 78.7 ± 3.2 kg (range, 65-104 kg)] volunteered to participate. Nine of the subjects participated in the first protocol focused on the effects of muscle contraction vs. vasodilator-induced BF increase. Their mean thigh volume was 8.17 ± 0.40 liters (range, 6.75-9.46 liters), as estimated from anthropometric measurements from patella to os pubis (3, 12). Five other subjects were studied in a second protocol to compare the effects of passive vs. voluntary contractions. Before the experiments began, the subjects were informed about the experimental procedures, the potential risks, and discomfort. They were told that they could withdraw at any time without any consequences. They participated after having first signed informed consent. The experiments were carried out with the approval of the Ethical Committees of Copenhagen and Fredriksberg (KF-01-013/96).
Experimental procedures. Before the experiments, the subjects were familiarized with the one-legged, dynamic, thigh muscle exercise. They trained on an ergometer (2) at 60 rpm, kicking forward and backward, using their hamstring and quadriceps muscles. The mean peak power output that they could sustain for 3 min at 60 rpm was 68.9 ± 4.5 W (range, 50-90 W), as determined from an incremental exercise protocol starting at 10 W and increasing with 5- to 10-W increments every third minute.
All subjects were required to abstain from caffeine, tea, and nicotine for at least 48 h before the experiments. Subjects reported to the laboratory at 0800. After 30 min of supine bed rest, they were given local anesthesia (lidocaine, 20 mg/ml); the femoral arteries of both legs and the femoral vein of one leg were cannulated in each subject. Catheters (20 gauge, Ohmeda, Wiltshire, UK) were inserted ~2-5 cm below the inguinal ligament with the use of the Seldinger technique. One arterial catheter was used for drug infusion during rest and exercise. The other arterial catheter was used to monitor blood pressure and to sample blood, thus allowing these measurements to be performed without interrupting the drug infusion. The tip of the femoral arterial catheter for drug infusion was specifically positioned right above the femoral bifurcation. Arterial and venous blood samples were drawn and analyzed for hemoglobin, oxygen saturation (AVL 912 CO-Oxylite; AVL Medical Instruments, Schaffhausen, Switzerland), and hematocrit. Femoral artery BF (BFFA) was measured distal to the inguinal ligament by Doppler ultrasound (23). Heart rate, electrocardiogram, and arterial blood pressure were continuously monitored (Dialogue 2000; Danica Elektronik, Copenhagen, Denmark). A Harvard syringe pump (model 44, Harvard Apparatus, South Natick, MA) was used for infusion of Ado (Item Development, Stocksund, Sweden). Limb oxygen uptake (
O2) was calculated by
multiplying the measurements of
BFFA inflow
(BFFA,i) with the arterial and
venous difference in oxygen content (Fick's principle).
Microdialysis. Using local anesthesia (lidocaine, 20 mg/ml) of the skin and subcutaneous tissue, we inserted three to six single- and double-lumen microdialysis probes into the vastus lateralis muscle of the quadriceps femoris group. The insertions were performed with an initial insertion angle of ~45°, moving proximally and laterally in a direction estimated to be parallel with the muscle fiber direction. The single-lumen probe was constructed by a microdialysis fiber, with a molecular cutoff at 5-6 kDa, obtained from an artificial kidney dialysis machine (GFS 16-GFE 18; Gambro, Lund, Sweden). Each end of the fiber (0.20 mm ID, 0.22 mm OD) was inserted and secured 1 cm into a hollow nylon tube (Portex; Hythe, Kent, UK). This resulted in a microdialysis membrane length for diffusion of 40 mm and inlet and outlet tubings (0.50 mm ID, 0.63 mm OD) with lengths of 10 and 6 cm, respectively, through which the infusate and dialysate could perfuse. The tensile strength of the probe was increased by attaching a coated vinyl suture thread (5-0, Ethicon; Johnson & Johnson, Sommerville, NJ) between the tubings. The double-lumen probe (CMA 60; CMA Microdialysis, Solna, Sweden) was constructed by an inlet and outlet tubing (polyurethane) attached to two concentric cylinders. The inner cylinder was extended distally inside the outer one, consisting of the 30-mm microdialysis membrane (polyamide; 0.52 mm OD) with a molecular cutoff at 20 kDa. Schematic figures of the two different types of probes have previously been shown in an article by Arner and Bolinder (4).
The probes were perfused with a microdialysis pump (CMA 102; CMA Microdialysis) at a rate of 5.0 µl/min. The infusate was an isotonic Ringer acetate solution (Pharmacia, Stockholm, Sweden) in which 3.0 mM glucose, 0.5 mM lactate, and 5.0 mM ethanol were dissolved; 2.7 nM [2-3H]Ado and 0.18 µM D-[14C(U)]glucose (both from Amersham Life Sciences, Buckinghamshire, UK) were also added. The specific activities in their standard solutions were 740 and 11.2 GBq/mmol, respectively. The probes were perfused for
1 h before
the start of the experimental collection of
microdialysate. The dialysate, excluding the dead volume
of the probe and tubing, was collected throughout each experimental session. The dialysate was subsequently weighed, and the actual flow
rate was calculated to estimate any loss of fluid or abnormal decrease
in perfusion rate. Only probes with a calculated perfusion rate in the
range of 4.5-5.0 µl/min were accepted. The collection tubes were
immediately capped, stored in a freezer, and analyzed within 24 h. The
[ethanol] was measured according to the procedures of
Hickner et al. (10). The ethanol outflow-to-inflow ratio ([ethanol]dialysate/[ethanol]infusate)
was calculated from the [ethanol] in the dialysate and
infusate, respectively (10). Moreover, the probes were perfused at a
rate giving an initial ethanol outflow-to-inflow ratio within the
previously defined sensitive range of 25-45% (9). The molecular
PR [PR = (dpminfusate 
dpmdialysate) / dpminfusate],
where dpm denotes disintegrations per minute, was determined according
to the internal reference method (15, 17, 28) for two different
molecules, e.g.,
[2-3H]Ado and
D-[14C(U)]glucose.
The 3H and
14C activities (in dpm) were
measured on a liquid scintillation counter (Tri-Carb 2000; Copenhagen;
Denmark) after addition of the infusate and dialysate (10 µl each) to 3.0 ml of Ultima Gold scintillation liquid (Packard
Instruments, Gronningen, The Netherlands).
BFFA.
The equipment and procedures of measurement of femoral artery BF have
been described previously (23). In brief, the instrument used was a
Doppler ultrasound (model CFM 800, Vingmed Sound, Horten, Norway)
equipped with an annular phased-array transducer (Vingmed Sound) probe
(11.5-mm diameter), operating at an imaging frequency of 7.5 MHz and
variable Doppler frequencies of 4.0-6.0 MHz (high-pulsed repetition frequency mode of 4-36 kHz). The vessel diameter
[cross-sectional area
(A)] and blood velocity
(v) were measured in the common
femoral artery, distal to the inguinal ligament but above the
bifurcation into the superficial and profunda femoral branch. The
femoral arterial inflow (BFFA = 6 · 104 · vmean · A,
in l/min) of blood to the leg was calculated, over the velocity
profile, by multiplying the cross-sectional area (A = 
· r2,
in m2) of the femoral artery
with the angle-corrected, time- and space-averaged, and amplitude
(signal intensity)-weighted mean blood velocity (vmean, in m/s).
A cuff just below the knee was temporarily inflated before the flow
measurements to a suprasystolic blood pressure (>240 mmHg) to
eliminate contributions to and contaminations from the lower leg.
Experimental protocol.
The first protocol consisted of six interventions.
1 and
2) Two consecutive rest control
sessions were followed by infusion of Ado in the femoral artery
(AdoFA,i) at rest at rates of
3) 125 µg · min1 · l1
thigh volume (low dose,
AdoFA,i low) and
subsequently 4) 1,000 µg · min1 · l1
thigh volume (high dose,
AdoFA,i high), dynamic
thigh muscle exercise at 28.6 ± 1.4 W
5) without and thereafter
6) with infusion of
AdoFA,i high. Each
intervention lasted for 28-30 min, and interventions were
separated by 30 min of rest, i.e., until the
BFFA had normalized at control
level [P = not statistically
significant (NS)]. The microdialysis dialysate was collected at the
end of each intervention. Blood samples were drawn before, in the
middle, and at the end of the sessions.
BFFA was specifically measured
before and at the start of each intervention, as well as in the
middle and at the end of each intervention. The
BFFA and
O2 measurements in the
middle were not significantly different from those at the end of each
session (P = NS). Each subject
performed the exercise with the thigh in the horizontal position and
with the upper body tilted ~140° backward. In the second
protocol, the effect of passive leg movement on ethanol removal and PR
of
D-[14C(U)]glucose
was compared with voluntary exercise in five subjects. The passive leg
movement was performed by moving the subject's leg, attached to the
ergometer lever arm, at 60 rpm for ~20 min.
Statistics. Parametric statistics were used for data analysis. Multiple ANOVAs for repeated measures and Tukey honestly significant difference post hoc tests were used when comparing more than two conditions over time. Pearson correlation and linear regression were used to study the association between variables. A P value < 0.05 was considered as statistically significant. The values in the text are given as means ± SE.
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RESULTS |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Vascular response and leg
O2.
In the two control periods at rest,
BFFA was the same (0.16 ± 0.03 l/min, P = NS; Fig.
1A).
When Ado was infused in the femoral artery at rest at rates of 125 and
1,000 µg · min1 · l1
thigh volume (AdoFA,i low
and AdoFA,i high,
repectively), BFFA was elevated to
1.80 ± 0.26 and 4.86 ± 0.53 l/min, respectively (P < 0.01; Fig.
1A). Exercise increased
BFFA to 3.79 ± 0.37 l/min, and
AdoFA,i high during exercise
elevated BFFA further to 6.13 ± 0.65 l/min (P < 0.01; Fig.
1A).
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O2 was similar during
the two control periods at rest as well as during
AdoFA,i low and
AdoFA,i high at rest (12 ± 1 ml/min; P = NS). This was
caused by a concomitant decrease in the
O2 extraction during
AdoFA,i
(P < 0.01). The leg
O2 increased during exercise
(P < 0.01) to a similar
level of 470 ± 53 and 493 ± 52 ml/min without and with
AdoFA,i high, respectively
(P = NS).
Ethanol outflow-to-inflow ratio. The ethanol outflow-to-inflow ratio (38.3 ± 2.3%) was similar during the two control periods at rest and did not change during AdoFA,i low and AdoFA,i high at rest (P = NS; Fig. 1B). During exercise, the ethanol outflow-to-inflow ratio decreased (P < 0.01) to a similar level of 17.5 ± 3.4 and 20.6 ± 3.2% without and with AdoFA,i high, respectively (P = NS; Fig. 1B).
The ethanol outflow-to-inflow ratio did not correlate with the increase in BFFA induced by AdoFA,i low and AdoFA,i high at rest (P = NS; Fig. 2A). However, the ethanol outflow-to-inflow ratio correlated inversely with the changes in BFFA from rest control to exercise without (r =0.83) and with (r = 0.67) AdoFA,i high, respectively (P < 0.001).
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PR. The PR values for both [2-3H]Ado (35.4 ± 1.6%) and D-[14C(U)]glucose (15.9 ± 1.1%) were similar, respectively, during the two control periods at rest and did not change during the AdoFA,i low and AdoFA,i high at rest (P = NS; Fig. 1, C and D). During exercise without and with AdoFA,i high, the PR for [2-3H]Ado increased (P < 0.01) to a similar level of 55.8 ± 2.8 and 61.2 ± 2.5% (P = NS), respectively, whereas the PR for D-[14C(U)]glucose increased (P < 0.01) to a similar level of 42.8 ± 3.9 and 45.2 ± 5.1% (P = NS), respectively (Fig. 1, C and D).
The PR for [2-3H]Ado and D-[14C(U)]glucose did not correlate with the increase in BFFA at rest induced by AdoFA,i low and AdoFA,i high (P = NS; Fig. 2, B and C). However, the PR for [2-3H]Ado and D-[14C(U)]glucose correlated positively with the changes in BFFA from rest control to exercise, both without (r = 0.69 for [2-3H]Ado; r = 0.90 for D-[14C(U)]glucose) and with AdoFA,i high (r = 0.74 for [2-3H]Ado; r = 0.88 for D-[14C(U)]glucose; P < 0.001). Moreover, the PR for [2-3H]Ado and D-[14C(U)]glucose correlated with each other from rest control to exercise without (r = 0.75) and with (r = 0.80) AdoFA,i high (P < 0.001). The ethanol outflow-to-inflow ratio correlated inversely with the PR for [2-3H]Ado and D-[14C(U)]glucose from rest control to exercise without (r =0.58 for
[2-3H]Ado;
r = 0.87 for
D-[14C(U)]glucose)
and with AdoFA,i high
(r = 0.58 for
[2-3H]Ado;
r = 0.78 for
D-[14C(U)]glucose;
P < 0.001; Fig.
3).
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Passive vs. voluntary contractions. Passive leg movement, with muscle shortening and lengthening, decreased the ethanol outflow-to-inflow ratio from 35.1 ± 1.7 to 28.0 ± 1.4% (P < 0.01), whereas the PR values for D-[14C(U)]glucose increased from 25.0 ± 1.8 to 34.0 ± 1.6% (P < 0.001). During voluntary exercise, the ethanol outflow-to-inflow ratio further decreased to 20.5 ± 1.5% in association with an increase in D-[14C(U)]glucose PR to 43.2 ± 0.9% (P < 0.05).
The mean coefficient of variation for the ethanol outflow-to-inflow ratio for the microdialysis probes within each subject was 12.4 ± 5.0, 14.4 ± 6.2, and 11.1 ± 3.5% (at rest and during passive and voluntary exercise, respectively) and 9.7 ± 4.4, 10.3 ± 0.9, and 6.4 ± 0.3%, for the D-[14C(U)]glucose PR (at rest and during passive and voluntary exercise, respectively). Moreover, the mean coefficient of variation for the ethanol outflow-to-inflow ratio for all microdialysis probes was ~15.6, 15.4, and 23.5% (at rest and during passive and voluntary exercise, respectively) and ~22.3, 15.2, and 6.7% for the D-[14C(U)]glucose PR (at rest and during passive and voluntary exercise, respectively).| |
DISCUSSION |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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The present study demonstrates that major changes in limb BF are not associated with changes in the ethanol outflow-to-inflow ratio. On the other hand, the ethanol outflow-to-inflow ratio decreased during dynamic exercise in association with an increase in the molecular transport across the probe membrane, i.e., PR. The increased ethanol removal during exercise may, therefore, represent exercise-induced changes in PR rather than local muscle BF. Thus the result in the present study demonstrates that the ethanol outflow-to-inflow ratio is not a suitable indicator of muscle BF.
Our observation of a decrease in the ethanol outflow-to-inflow ratio during dynamic muscle contractions (Figs. 1 and 2) is in agreement with the inverse relationship between the ethanol outflow-to-inflow ratio and BF described by Hickner et al. (8) during intermittent contractions. Hickner et al. suggested that these changes in the ratio represented the local BF. However, our findings that major changes in limb BF induced by a pure vasodilatation are not associated with alterations in the ethanol outflow-to-inflow ratio, nor with any changes in the molecular transport across the membrane (PR), show that the ethanol outflow-to-inflow ratio does not purely reflect local BF (Figs. 1 and 2). On the other hand, the ethanol outflow-to-inflow ratio was closely associated with the PR, with an inverse correlation in transition from rest to exercise (Fig. 3). Thus the change in the ethanol outflow-to-inflow ratio most likely represents a change in the properties of the molecular transport, in the interstitium and across the microdialysis membrane, that is induced by the movement of the leg or the muscle contractions and relaxations. This may also explain why the ethanol-removal technique in previous studies has shown a nonlinearity and sensitivity differences over a wide range of muscle BF during exercise; in contrast, the muscle BF is known to increase linearly with increasing intensity (3, 23, 25). The study of Hickner et al. (9) is also of note. In addition to modulating BF in cat skeletal muscle by a servo-controlled roller pump, they added electrical stimulation of the sciatic nerve. Such an intervention, which induces contractions and relaxations, may thus per se decrease the ethanol outflow-to-inflow ratio.
What remains unresolved is why the PR is changed with muscle contractions and relaxations. The molecular transport across the probe membrane is known to be affected by the membrane length and the rate of diffusion in the interstitium, as well as the probe perfusion rate (1, 16, 20). Because the probe characteristics and perfusion rate were constant during rest and exercise, the changes in molecular transport may have been attributed to either the changes in BF or other factors that affect the transport across the membrane. In light of the finding that both the ethanol outflow-to-inflow ratio and PR were independent of a pure vasodilatation, the inverse correlation between the ethanol outflow-to-inflow ratio and the PR in transition from rest to exercise may reflect the effect of the muscle contractions and relaxations per se.
The association between the changes in ethanol outflow-to-inflow ratio and PR in transition from rest to passive leg movement, which is further enhanced during voluntary contractions, may reflect the intramuscular pressure oscillations previously observed to increase accordingly from rest to passive and to voluntary exercise (Fig. 4) (24). It is possible that these intramuscular pressure variations and the muscle motion have a stirring effect in the muscle and thereby alter the molecular transport in the interstitium. It is also possible that a squeezing of the probe membrane may modulate the molecular transport over the microdialysis membrane. However, it has not been investigated in the past and remains to be elucidated whether these factors influence the diffusion rate, diffusion path length, and the diffusible interstitial volume fraction. Moreover, the slight (3- to 5-fold BF increase) induced by passive leg movement was also smaller than the observed Ado-induced BF increase, which had no effect on the molecular transport. It is therefore more likely that the changes in molecular transport are caused by the muscle contractions and relaxations per se rather than by BF changes.
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In conclusion, the present study raises some fundamental questions on how to interpret the changes in the microdialysis ethanol removal during exercise. The ethanol outflow-to-inflow ratio does not seem to reflect local skeletal muscle BF but instead changes in molecular transport across the microdialysis membrane, induced by the leg movements or muscle contractions and relaxations per se. The results of the present study further demonstrate that the PR appears to be independent of muscle BF.
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ACKNOWLEDGEMENTS |
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Adenosine was kindly provided by Item Development (Stocksund, Sweden).
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FOOTNOTES |
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The present work was financially supported by a grant from the Danish National Research Foundation (504-14).
Address for reprint requests: G. Rådegran, Copenhagen Muscle Research Centre, Rigshospitalet, Section 7652, Tagensvej 20, DK-2200 Copenhagen N, Denmark (E-mail: goran{at}rh.dk).
Received 15 December 1997; accepted in final form 7 April 1998.
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REFERENCES |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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1.
Amberg, G.,
and
N. Lindefors.
Intracerebral microdialysis. II. Mathematical studies of diffusion kinetics.
J. Pharmacol. Methods
22:
157-183,
1989[Medline].
2.
Andersen, P.,
R. P. Adams,
G. Sjøgaard,
A. Thorboe,
and
B. Saltin.
Dynamic knee extension as model for study of isolated exercising muscle in humans.
J. Appl. Physiol.
59:
1647-1653,
1985
3.
Andersen, P.,
and
B. Saltin.
Maximal perfusion of skeletal muscle in man.
J. Physiol. (Lond.)
366:
233-249,
1985
4.
Arner, P.,
and
J. Bolinder.
Microdialysis of adipose tissue.
J. Intern. Med.
230:
381-386,
1991[Medline].
5.
Black, J. E.
Blood flow requirements of the human calf after walking and running.
Clin. Sci. (Lond.)
18:
89-93,
1959[Medline].
6.
Bonde-Petersen, F.,
and
J. Siggaard-Andersen.
Simultaneous venous occlusion plethysmography and Xe133 clearance in patients with arteriosclerosis of the lower extremities. An attempt to evaluate the blood flow in skin and muscle.
Scand. J. Thorac. Cardiovasc. Surg.
3:
20-25,
1969[Medline].
7.
Clausen, J. P.,
and
N. A. Lassen.
Muscle blood flow during exercise in normal man studied by the 133-Xenon clearance method.
Cardiovasc. Res.
5:
245-254,
1971
8.
Hickner, R. C.,
D. Bone,
U. Ungerstedt,
L. Jorfeldt,
and
J. Henriksson.
Muscle blood flow during intermittent exercise: comparison of the microdialysis ethanol technique and 133Xe clearance.
Clin. Sci. (Colch.)
86:
15-25,
1994[Medline].
9.
Hickner, R. C.,
U. Ekelund,
S. Mellander,
U. Ungerstedt,
and
J. Henriksson.
Muscle blood flow in cats: comparison of microdialysis ethanol technique with direct measurement.
J. Appl. Physiol.
79:
638-647,
1995
10.
Hickner, R. C.,
H. Rosdahl,
I. Borg,
U. Ungerstedt,
L. Jorfeldt,
and
J. Henriksson.
The ethanol technique of monitoring local blood flow changes in rat skeletal muscle: implications for microdialysis.
Acta Physiol. Scand.
146:
87-97,
1992[Medline].
11.
Hickner, R. C.,
U. Ungerstedt,
and
J. Henriksson.
Regulation of skeletal muscle blood flow during acute insulin-induced hypoglycemia in the rat.
Diabetes
43:
1340-1344,
1994[Abstract].
12.
Ingemann-Hansen, T.,
and
J. Halkjaer-Kristensen.
Lean and fat component of the human thigh. The effects of immobilization in plaster and subsequent physical training.
Scand. J. Rehabil. Med.
9:
67-72,
1977[Medline].
13.
Iversen, P. O.,
and
G. Nicolaysen.
Heterogenous blood flow distribution within single skeletal muscles in the rabbit: role of vasomotion sympathetic nerve activity and effect of vasodilation.
Acta Physiol. Scand.
137:
125-133,
1989[Medline].
14.
Iversen, P. O.,
M. Standa,
and
G. Nicolaysen.
Marked regional heterogeneity in blood flow within skeletal muscle at rest and during exercise hyperaemia in the rabbit.
Acta Physiol. Scand.
136:
17-28,
1989[Medline].
15.
Jansson, P.-A.,
T. Veneman,
N. Nurjhan,
and
J. Gerich.
An improved method to calculate adipose tissue interstitial substrate recovery for microdialysis studies.
Life Sci.
54:
1621-1624,
1994[Medline].
16.
Kehr, J.
A survey on quantitative microdialysis: theoretical models and practical implications.
J. Neurosci. Methods
48:
251-261,
1993[Medline].
17.
Kurosawa, M.,
Å. Hallström,
and
U. Ungerstedt.
Changes in cerebral blood flow do not directly affect in vivo recovery of extracellular lactate through microdialysis probe.
Neurosci. Lett.
126:
123-126,
1991[Medline].
18.
Lassen, N. A., O. Henriksen, and P. Sejrsen.
Indicator methods for measurement of organ and tissue blood flow.
In: Handbook of Physiology. The Cardiovascular System.
Peripheral Circulation and Organ Blood Flow. Bethesda,
MD: 1983, sect. 2, vol. III, pt. 1, chapt. 2, p. 21-63.
19.
Laughlin, M. H.,
and
R. B. Armstrong.
Muscular blood flow distribution patterns as a function of running speed in rats.
Am. J. Physiol.
243 (Heart Circ. Physiol. 12):
H296-H306,
1982
20.
Lindefors, N.,
G. Amberg,
and
U. Ungerstedt.
Intracerebral microdialysis. 1. Experimental studies of diffusion kinetics.
J. Pharmacol. Methods
22:
141-156,
1989[Medline].
21.
Pendergast, D. R.,
J. A. Krasney,
A. Ellis,
B. McDonald,
N. I. C. Marco,
and
P. Cerretelli.
Cardiac output and muscle blood flow in exercising dogs.
Respir. Physiol.
61:
317-326,
1985[Medline].
22.
Piiper, J.,
D. R. Pendergast,
C. Marconi,
M. Meyer,
N. Heisler,
and
P. Cerretelli.
Blood flow distribution in dog gastrocnemius at rest and during stimulation.
J. Appl. Physiol.
58:
2068-2074,
1985
23.
Rådegran, G.
Ultrasound Doppler estimates of femoral artery blood flow during dynamic knee extensor exrcise in man.
J. Appl. Physiol.
83:
1383-1388,
1997
24.
Rådegran, G.,
and
B. Saltin.
Muscle blood flow at onset of exercise.
Am. J. Physiol.
274 (Heart Circ. Physiol. 43):
H314-H322,
1998
25.
Richardson, R. S.,
D. C. Poole,
D. R. Knight,
S. S. Kurdak,
M. C. Hogan,
B. Grassi,
E. C. Johnson,
K. F. Kendrick,
B. K. Erickson,
and
P. D. Wagner.
High muscle blood flow in man: is maximal O2 extraction compromised?
J. Appl. Physiol.
75:
1911-1916,
1993
26.
Rosdahl, H.,
U. Ungerstedt,
L. Jorfeldt,
and
J. Henriksson.
Interstitial glucose and lactate balance in human skeletal muscle and adipose tissue studied by microdialysis.
J. Physiol. (Lond.)
471:
637-657,
1993
27.
Saltin, B.
Hemodynamic adaptions to exercise.
Am. J. Cardiol.
55:
42D-47D,
1985[Medline].
28.
Scheller, D.,
and
J. Kolb.
The internal reference technique in microdialysis: a practical approach to monitoring dialysis efficiency and to calculating tissue concentration from dialysate samples.
J. Neurosci. Methods
40:
31-38,
1991[Medline].
29.
Sejrsen, P.,
and
K. H. Tønnessen.
Shunting by diffusion of inert gas in skeletal muscle.
Acta Physiol. Scand.
86:
82-91,
1972[Medline].
30.
Tønnesen, K. H.
Blood-flow through muscle during rhythmic contraction measured by 133Xe.
Scand. J. Clin. Lab. Invest.
16:
646-654,
1964[Medline].
31.
Wallgren, F.,
G. Amberg,
R. C. Hickner,
U. Ekelund,
L. Jorfeldt,
and
J. Henriksson.
A mathematical model for measuring blood flow in skeletal muscle with the microdialysis ethanol technique.
J. Appl. Physiol.
79:
648-659,
1995
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