Vol. 275, Issue 1, R135-R140, July 1998
Chronic lymph flow responses to hyperproteinemia
R. Davis
Manning Jr.
Department of Physiology and Biophysics, University of
Mississippi Medical Center, Jackson, Mississippi 39216-4505
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ABSTRACT |
The long-term responses of lymph flow,
lymph protein transport, and the permeability-surface area (PS) product
to hyperproteinemia have been studied in conscious dogs. Plasma protein
concentration (PPC) was increased by daily intravenous infusion of
previously collected autologous plasma for 9 days. Lymph flow was
determined by collecting lymph chronically from a lymphatic afferent to
the popliteal node in the hind leg. Compared with the average value during the normal-PPC period, the following changes occurred during 10 days of high PPC: lymph flow decreased from 12.3 ± 1.1 to 3.8 ± 0.6 µl/min, lymph protein transport decreased from 241 ± 24 to
141 ± 21 µg/min, PS product decreased from 4.7 ± 0.5 to 3.0 ± 0.5 µl/min, PPC increased from 7.1 ± 0.1 to 8.8 ± 0.4 g/dl, lymph protein concentration increased from 1.9 ± 0.1 to 3.8 ± 0.1 g/dl, plasma colloid osmotic pressure increased from
18.6 ± 0.8 to 24.2 ± 2.1 mmHg, and lymph colloid
osmotic pressure increased from 4.8 ± 0.2 to 10.4 ± 0.7 mmHg.
In conclusion, long-term hyperproteinemia in dogs resulted in chronic
decreases in lymph flow, lymph protein transport, and the PS product
and chronic increases in lymph protein concentration and lymph colloid
osmotic pressure. The marked decrease in lymph flow during
hyperproteinemia decreased lymph protein transport and thus contributed
to the increase in lymph protein concentration. In addition, the
decreases in PS product and lymph protein transport suggest that
transcapillary protein flux decreases during hyperproteinemia.
colloid osmotic pressure; permeability-surface area product; lymph
protein transport; extracellular fluid volume
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INTRODUCTION |
SEVERAL STUDIES HAVE INDICATED that the
lymphatic system plays an important role in the control of
extracellular fluid volume during hypertension (22, 23), after
hemorrhage (12), and during hypoproteinemia (4, 10). Our previous
studies showed that during moderate hypoproteinemia blood volume
decreases very little (15), and extracellular fluid volume increases
only mildly because of a decrease in interstitial protein concentration
(1, 24). The decrease in interstitial protein concentration in this condition has been referred to as a "wash-down phenomenon" and is
caused by an increase in lymph flow that returns interstitial protein
to the circulation and thus depletes the interstitial protein.
Therefore, increased lymph flow results in a decrease in interstitial
protein concentration during hypoproteinemia and thus helps to prevent
edema formation.
Although significant hyperproteinemia occurs in multiple myeloma,
sarcoidosis, lymphogranuloma, liver diseases, parasitic conditions, and
dehydration (3), no studies have determined the lymph flow responses to
chronic increases in plasma protein concentration (PPC). A study in our
laboratory has shown that prenodal lymph protein concentration
increases markedly in dogs with chronic hyperproteinemia (14). However,
lymph was collected acutely during anesthesia (14), which could have
affected lymph protein concentration, and lymph flow was not
determined. A previous acute study in cats showed that intravenous
infusion of albumin causes marked increases in plasma colloid osmotic
pressure and large decreases in the lymph flow and the capillary
filtration coefficient (CFC) of an intestinal segment (8). In this
study, the net capillary filtration pressure was normal 2 h after the albumin infusion, but lymph flow and the CFC decreased 75% (8). However, whether lymph flow remains at subnormal levels during chronic
increases in PPC is not known. The goal of this study was to test the
hypothesis that lymph flow decreases chronically during
hyperproteinemia, which will reduce lymph protein transport and thus
allow lymph protein concentration to increase. Therefore, the responses
of lymph flow, lymph protein transport, and the permeability-surface
area (PS) product to chronic hyperproteinemia were studied in the long
term in conscious dogs in which PPC was elevated by daily intravenous
infusion of previously collected autologous plasma.
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METHODS |
Animal preparation and experimental protocol.
Experiments were performed over a 23-day period on five conscious dogs
with an average body weight of 31.2 ± 3.3 kg. The project had the
approval of the local Institutional Animal Committee. All dogs were
splenectomized and equipped with chronic arterial and venous catheters
and a chronic catheter in a prenodal lymphatic afferent to the
popliteal lymph node in the hind leg.
During the first surgical procedure, a splenectomy was performed
through a midline abdominal incision and catheters were implanted in
the aorta and inferior vena cava through the femoral artery and vein.
Aseptic technique was used in all surgical procedures, and atropine
sulfate (1 ml of 0.4 mg/ml im; Elkins-Sinn, Cherry Hill, NJ) was
administered before surgery. Anesthesia was initiated with thiopental
sodium (Pentothal, 25 mg/kg iv; Abbott Laboratories, North Chicago, IL)
and maintained with a mixture of methoxyflurane (Penthrane, Abbott
Laboratories) and oxygen. Appropriate gas concentrations were delivered
to the dogs through an endotracheal tube connected to an Ohio Medical
Products anesthesia machine (Kinet-O-Meter). The catheters were
tunneled subcutaneously and exited the back between the dogs'
shoulders. A period of 10-14 days of recovery followed surgery,
during which the dogs were trained to lie quietly in their cages. Water
intake was ad libitum throughout the experiment. Sodium intake was
maintained at ~75 meq/day during the control period
(days
1-7)
and the normal-PPC period (days
19-23)
by feeding the dogs 894 g/day of K/D prescription diet dog food (Hills
Pet Food) to which 45 meq of sodium chloride (9 ml of 5 M NaCl) was added. During the first 9 days of the high-PPC period
(days
8-16), the same sodium intake was achieved by intravenous infusion of an
average of 330 ml/day of previously collected autologous plasma, which
contained ~45 meq of sodium, and the dogs were fed 894 g/day of P/D
prescription diet dog food (Hills Pet Food). On the last day of the
high-PPC period (day
17), the dogs were fed 894 g of P/D
dog food to which 45 meq of sodium was added, but no plasma was
infused.
After the surgical recovery period, plasma was collected 5 days a week
by plasmapheresis over a 3-wk period, and the plasma was stored at
20°F. This procedure has been previously described in detail
(13, 14). After completion of the plasmapheresis period, a 17-day
recovery period was afforded before the experiment was begun, which
allowed the PPC of the dogs to return to normal levels. Then data were
collected during a control period
(days 1-7),
a period of high PPC (days
8-16),
a plasmapheresis day (day 18), and a normal-PPC period
(days
19-23).
The PPC of the dogs was elevated during the first 9 days of the
high-protein period by infusing, by intravenous drip in 1 h, ~330 ml
of previously collected autologous plasma. On
day
16 during the high-protein period, the
dogs were anesthetized as before, and a catheter was implanted in a
prenodal lymphatic afferent to the popliteal node in the hind leg of
the dog. Lymph flow was measured and lymph was collected four times the
next day (day
17). In one of the dogs, the lymph
initially contained red blood cells, and data obtained from lymph
collection on this dog from this point in time were not used. Then, on
day
18, plasmapheresis was performed to
reduce PPC to normal, and after 24 h
(day
19), lymph flow and lymph protein
concentration were determined four times a day for the next 4 days. An
additional plasmapheresis was performed on day
21 on two dogs because their PPC was
slightly higher than their average value during the control period.
The lymphatic catheter was constructed with polyethylene (PE-50; Clay
Adams) and Silastic (0.020 in. ID × 0.037 in. OD; Dow Corning)
and was pretreated with the polymer coating material TDMAC
heparin as described previously (21). The free end of the catheter was
exteriorized in the inner aspect of the hind limb where it was
connected to a collection vial. Next, the tip of the catheter was
placed at the level of the cannulated lymphatic, and lymph from the
prenodal lymphatic was collected continuously for 4 days. To prevent
clotting of the lymphatic catheter, the dogs received a continuous
intravenous heparin infusion (120 U · kg
1 · day1).
Experimental measurements and instrumentation.
The dogs were housed in metabolic cages and were fitted with a backpack
that held a Statham P23 AC or a P23 ID transducer at the level of the
heart. The transducer wires were connected to a Grass model 7D recorder
that was connected to a digital computer. Every minute throughout the
day the computer sampled arterial pressure 500 times in a 3-s period,
and the average was stored on a computer disk (17).
Plasma and lymph protein concentrations were measured with an American
Optical refractometer, and plasma colloid osmotic pressure was
determined with a colloid osmometer originally developed in this
department by Prather et al. (18). During the high-PPC period, plasma
protein and colloid osmotic pressures were measured before the daily
plasma infusions. The PS product for the hind limb under study was
calculated by an equation developed previously (2, 21)
where
PLF is the peripheral lymph flow and L/P is the lymph-to-PPC ratio. In
this calculation, the passage of protein across the microvasculature is
assumed to occur only by diffusion, and any protein transport due to
convection is neglected (2, 19, 21). Lymph protein transport was
calculated by multiplying lymph protein concentration and lymph flow.
Statistical analysis was performed by first determining overall
significance with analysis of variance for repeated measures. Second,
significance on the individual experimental days was determined post
hoc with Dunnett's test for multiple comparisons with a control (5).
The data were considered statistically significant if P < 0.05. All data are expressed as
means ± SE.
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RESULTS |
Responses of PPC, plasma colloid osmotic pressure, mean arterial
pressure and hematocrit to hyperproteinemia.
PPC averaged 6.8 ± 0.3 g/dl during the control period and increased
rapidly during the 10-day period of hyperproteinemia as shown in Fig.
1. By day
10, PPC had significantly increased
and remained elevated throughout the remainder of the high-PPC period. By day
17, PPC reached a value of 8.8 ± 0.4 g/dl, and PPC averaged 7.1 ± 0.1 g/dl during the 5-day
normal-PPC period. Plasmapheresis was performed on
day
18 and reduced the PPC back to values
not significantly different from control.
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Fig. 1.
Line graphs show responses of plasma protein concentration (PPC),
plasma colloid osmotic pressure, and the 24-h average of mean arterial
pressure to hyperproteinemia produced by daily intravenous infusion of
previously collected autologous plasma. Data were collected during a
7-day control period, a 10-day high-PPC period, and a 5-day normal
(Nor)-PPC period. Plasmapherisis was conducted on
day 18 (not shown) and
day 21 (2 dogs) to reduce PPC to control
value. * P < 0.05 compared
with average control value.
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Plasma colloid osmotic pressure also increased markedly during the
high-PPC period. As seen in Fig. 1, plasma colloid osmotic pressure
averaged 18.6 ± 0.8 mmHg during the normal-PPC period. During the
high-PPC period, plasma colloid osmotic pressure increased to 24.2 ± 2.1 mmHg on day
17 (P < 0.05). Therefore, plasma colloid osmotic pressure increased 5.6 mmHg by day
17 compared with the average value
during the normal-PPC period. During the normal-PPC period
(days
19-23),
the plasma colloid osmotic pressure was not significantly different
from the average value during the control period
(days
1-7).
Also seen in Fig. 1, mean arterial pressure averaged 79 ± 3 mmHg
during the control period and did not significantly change from this
value throughout the experiment.
Hematocrit measured on day
17 (high PPC) was 27.3 ± 2.7 and on day
19 (normal PPC) was 27.8 ± 2.4 (P not significant). This provides
evidence that blood volume did not change during hyperproteinemia in
the present experiment, which confirms our previous results (14).
Responses of lymph flow, lymph protein transport, and the PS product
to hyperproteinemia.
Figure 2 shows that lymph flow averaged 3.8 ± 0.6 µl/min on day
17 in the high-PPC period and
increased significantly to an average value of 12.3 ± 1.1 µl/min
during the entire normal-PPC period. By
day
19 when PPC had decreased to normal,
the lymph flow increased to 10.6 ± 2.2 µl/min
(P < 0.05) and was significantly increased throughout the remainder of the normal-PPC period. Lymph protein transport, also shown in Fig. 2, averaged 141 ± 21 µg/min on day
17 in the high-PPC period and 241 ± 24 µg/min (P < 0.05) during
the entire normal-PPC period. Also, lymph protein transport significantly increased on day
20, and the value was 307 ± 63 µg/min.
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Fig. 2.
Bar graphs show responses of lymph flow, lymph protein transport, and
the permeability-surface area (PS) product to high PPC and normal PPC.
Plasmapherisis was conducted on day 18 (not shown) and
day 21 (2 dogs) to reduce PPC to control
value. * P < 0.05 compared
with average value on day 17.
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Figure 2 also shows that the PS product averaged 3.0 ± 0.5 µl/min on day
17 in the high-PPC period. By
day
20 in the normal-PPC period, the PS
product increased to 6.0 ± 1.2 µl/min
(P < 0.05), and the average value of
PS during the entire normal-PPC period was 4.7 ± 0.5 µl/min,
which was significantly increased compared with
day
17 in the high-PPC period. The
lymph-to-plasma concentration ratio was 0.44 ± 0.001 on
day
17 during high PPC and averaged 0.273 ± 0.001 during the normal-PPC period
(P < 0.05).
Responses of prenodal lymph protein concentration and prenodal lymph
colloid osmotic pressure to hyperproteinemia.
As seen in Fig. 3, lymph protein
concentration averaged 3.8 ± 0.1 g/dl on
day
17 in the high-PPC period. Then
plasmapheresis was performed the following day, and data for
day
19 were taken the day after
plasmapheresis. Plasmapheresis reduced the lymph protein concentration
significantly, and on day
19 the prenodal lymph protein
concentration averaged 1.9 ± 0.1 g/dl
(P < 0.05 compared with
day
17). The average lymph protein
concentration for the entire normal-PPC period was 1.9 ± 0.1 g/dl
(P < 0.05).
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Fig. 3.
Bar graphs show responses of prenodal lymph protein
concentration and prenodal lymph colloid osmotic pressure to high PPC
and normal PPC. Plasmapherisis was conducted on
day 18 (not shown) and
day 21 (2 dogs) to reduce PPC to control
value. * P < 0.05 compared
with average value on day 17.
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Figure 3 also shows that prenodal lymph colloid osmotic pressure
increased markedly during the high-PPC period. Lymph colloid osmotic
pressure averaged 10.4 ± 0.7 mmHg on
day
17, and by
day 19 the colloid osmotic pressure of the
lymph had decreased to 4.7 ± 0.3 mmHg
(P < 0.05) and remained
significantly decreased throughout the remainder of the normal-PPC
period. The average value of lymph colloid osmotic pressure during the
normal-PPC period was 4.8 ± 0.2 mmHg
(P < 0.05 compared with
day
17). Therefore, lymph colloid
osmotic pressure was 5.6 mmHg higher on
day
17 than the average value during the
normal-PPC period.
Relationship between lymph protein concentration and PPC.
Figure 4 shows that the increased PPC was
significantly associated with an increased lymph protein concentration
(P < 0.05). This relationship was
plotted for dogs in this experiment with normal PPC and during
hyperproteinemia caused by infusion of autologous plasma for 9 days and
suggests that high PPC results in an increase in the concentration of
protein in the peripheral lymphatics.
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Fig. 4.
Linear regression relating PPC and lymph protein concentration in dogs
with normal PPC and with hyperproteinemia produced by daily intravenous
infusion of previously collected autologous plasma. Regression is
statistically significant (P < 0.01).
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Relationship between lymph colloid osmotic pressure and plasma
colloid osmotic pressure.
Figure 5 shows that increases in plasma
colloid osmotic pressure during the period of high PPC were
significantly associated with increases in lymph colloid osmotic
pressure (P < 0.01). The relationship was plotted for dogs in the experiment with normal PPC and
during the high-PPC period caused by intravenous infusion of autologous
plasma. The relationship suggests that increases in plasma colloid
osmotic pressure result in increases in lymph colloid osmotic pressure.
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Fig. 5.
Linear regression relating plasma colloid osmotic pressure and lymph
colloid osmotic pressure in dogs with normal PPC and with
hyperproteinemia produced by daily intravenous infusion of previously
collected autologous plasma. Regression is statistically significant
(P < 0.01).
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| |
DISCUSSION |
This study demonstrated for the first time that increases in PPC in
conscious dogs result in marked decreases in lymph flow, lymph protein
transport, and the PS product. Daily intravenous infusion of previously
collected autologous plasma resulted in several important changes.
Compared with the average values during the normal-PPC period, the data
on the last day of the high-PPC period
(day
17) showed that PPC increased 1.7 g/dl to a value of 8.8 ± 0.4 g/dl, prenodal lymph flow decreased
69%, lymph protein transport decreased 42%, PS product decreased
36%, and lymph protein concentration more than doubled. Therefore, the
interstitial-lymphatic system changed dramatically during chronic
hyperproteinemia.
The decrease in lymph flow during hyperproteinemia may have played a
major role in the increase in lymph protein concentration by removing
less protein from the interstitial spaces. In fact, lymph protein
transport on the last day of the high-PPC period (day
17) significantly decreased compared
with the average lymph protein transport during the normal-PPC period.
In further support of this hypothesis, previous studies have shown that
changes in lymph flow are accompanied by inverse changes in lymph
protein concentration. Increases in lymph flow during hypoproteinemia are accompanied by marked decreases in lymph protein concentration, thus "washing down the interstitium" (4, 10). On the other hand,
severe decreases or cessation of lymph flow in lymphedema causes large
increases in interstitial protein concentration (6).
Because we have previously shown that hyperproteinemia, produced in
dogs by the same techniques used in this study, caused only a small
increase in interstitial fluid volume (13, 14), the decrease in lymph
flow in the present study must have been accompanied by an
approximately equal decrease in transcapillary fluid flux. However, the
cause of this decreased fluid flux is not known. Starling (20)
originally showed that the transcapillary flux of fluid is proportional
to the CFC multiplied by the balance of hydraulic and colloid osmotic
pressures of the capillary and interstitium while assuming no changes
in crystalloid osmotic pressure across the capillary. In the absence of
changes in the CFC, an increase in plasma colloid osmotic pressure
should cause a decrease in the transcapillary flux of fluid across the
microvasculature because of an increased transcapillary colloid osmotic
pressure gradient. In fact, in acute experiments, an increase in blood colloids in animals (8) and humans (7) caused an increase in vascular
volume. However, intravascular colloids extravasate over time and begin
to appear within several hours in the interstitium. Indeed, in the
present experiment, plasma colloid osmotic pressure increased 5.6 mmHg
during the high-PPC period, and lymph colloid osmotic pressure
increased 5.6 mmHg. Therefore, these data suggest that interstitial
fluid colloid osmotic pressure increased and prevented changes in the
transcapillary colloid osmotic pressure gradient, which, in turn, would
prevent abnormal transcapillary fluid movement. This helps to explain
why blood volume was unchanged during chronic hyperproteinemia in a
previous study in our laboratory (14) and in the present study based on
a lack of change in hematocrit during high PPC.
Another factor that could have decreased transcapillary fluid flux is a
decrease in CFC, and several studies have shown that CFC may change
during changes in PPC. Intravenous administration of albumin into cats
caused an increase in lymph colloid osmotic pressure from 6.5 to 16 cmH2O in 2 h (8), and at this time the net capillary filtration pressure was at control levels, but both
lymph flow and CFC had decreased 75%. This importantly suggests that
decreases in the CFC may occur during hyperproteinemia, thus markedly
decreasing transcapillary fluid flux and therefore decreasing lymph
flow. Other evidence that the CFC may have decreased during hyperproteinemia comes from experiments that showed that perfusion of
frog capillaries without protein in the perfusate caused the hydraulic
conductivity of the capillaries to increase threefold (16), suggesting
that an increase in PPC may result in a decrease in CFC. Other studies
have shown that decreased plasma colloid osmotic pressure by
plasmapheresis may cause an increase in the CFC. Efferent lymph flow
from a prefemoral lymph node was elevated 24 h after plasmapheresis in
spite of normalized transcapillary Starling forces (9), suggesting that
transcapillary fluid flux increased during hypoproteinemia. Kramer et
al. (11) found that a decrease in plasma colloid osmotic pressure by
plasmapheresis was two times as effective as a rise in capillary
pressure in promoting lymph flow in the lung, suggesting an increase in
CFC. If the above-mentioned studies can be extrapolated to the present studies on hyperproteinemia, a decrease in CFC could have occurred and
contributed to the decrease in lymph flow.
One of the factors that could have decreased capillary hydraulic
conductivity, CFC, and lymph flow is an increase in viscosity of the
capillary filtrate or the lymphatic fluid. Studies on hypoproteinemia showed that lymph viscosity decreases during hypoproteinemia (11). Based on linear interpolation of plasma viscosity changes with changes
in PPC, calculated lymph viscosity during the normal-PPC period is 1.25 and during the high-PPC period is 1.75, a 40% increase in viscosity.
Therefore, the resistance to fluid filtration at the capillary as well
as resistance to lymph flow may have increased significantly because of
increased viscosity of the capillary filtrate and lymph, respectively,
both of which could have decreased lymph flow.
Another factor that could have decreased lymph flow during high PPC is
a decrease in interstitial fluid volume. However, interstitial fluid
volume likely increased in the present study, because in two previous
studies in our laboratory that used the same protocol to increase PPC,
extracellular fluid volume measured as sulfate space increased 12%
(14) or, measured as sodium iothalamate space, increased 11% (13).
Therefore, despite this likely increase in interstitial fluid volume,
lymph flow decreased, possibly because of decreases in CFC.
Yet another factor that could have affected lymph flow during high PPC
is a change in extracellular osmolality. However, plasma osmolality was
measured previously in our laboratory during chronic hyperproteinemia
in dogs, and no significant changes occurred when PPC was increased
(13, 14).
Lymph protein transport decreased in the present experiment during
hyperproteinemia, suggesting that the transcapillary protein flux also
decreased. One factor that could have decreased this protein flux is a
decrease in the PS product (2, 19, 21), which is a measure of the
diffusive capacity of the capillary membrane (19). The PS product
during hyperproteinemia on day 17 of the present experiment was 3.0 ± 0.5 µl/min, and this product increased significantly during the
normal-PPC period to a maximum value of 6.0 ± 1.2 µl/min on
day
20 and averaged 4.7 ± 0.5 µl/min for the entire normal-PPC period (P < 0.01). Therefore, decreases in either the permeability or the
surface area of the capillary membrane during hyperproteinemia may have
hindered transcapillary protein flux.
Reed et al. (19) recently measured the PS product with a new, precise
method in the dog hind paw and compared the results to the classical
Renkin estimate of PS product that we used in the present paper. Both
methods gave the exact same value for PS, which, according to Reed et
al. (19), "indicates that diffusional transcapillary flux of protein
predominates at normal lymph flows in these experiments."
Transcapillary flux of protein by diffusion likely dominated at the low
to normal lymph flows that occurred in the present experiment;
therefore, the calculated PS may be very close to the true value of PS.
Only at high capillary hydrostatic pressures and thus high lymph flows
does the transcapillary convection of protein play an important role in
the transcapillary protein flux (19).
In a previous study in our laboratory, prenodal lymph acutely collected
during anesthesia and with massage of the forelimb demonstrated that
lymph protein concentration increased from a control value of 1.6 g/dl
to 5.1 ± 0.08 g/dl during hyperproteinemia (14). The
lymph protein concentration did not increase as much in the present
studies because of several possible reasons:
1) PPC increased to 9.3 g/dl in the
previous study compared with 8.8 g/dl in the present study, and
2) lymph collected acutely during
anesthesia in the previous study may have overestimated the true lymph
protein concentration because of the short collection period, forelimb
massage rate, or the effects of anesthesia.
In conclusion, hyperproteinemia produced in conscious dogs by daily
intravenous infusion of autologous plasma resulted in chronic decreases
in lymph flow, lymph protein transport, and the PS product and chronic
increases in prenodal lymph protein concentration and lymph colloid
osmotic pressure. The marked decrease in PLF could have been due to a
decrease in CFC, as seen in acute experiments (9, 11, 16). This
decrease in lymph flow, produced by removing less protein from the
interstitium, could have contributed to the decreased lymph protein
transport and thus may have contributed to the increase in lymph
protein concentration (4, 6, 10, 11). In addition, a likely decrease in
capillary protein permeability, as reflected in the decreased PS
product, could have contributed to the decrease in lymph protein
transport. This increase in lymph protein concentration and,
supposedly, interstitial protein concentration, prevented any changes
in the transcapillary colloid osmotic pressure gradient and thus may
have helped to prevent any changes in blood volume and mean arterial
pressure.
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ACKNOWLEDGEMENTS |
I thank Ivadelle Heidke for typing the paper.
| |
FOOTNOTES |
This research was supported by National Heart, Lung and Blood Institute
grant HL-51971 and HL-11678.
Address for reprint requests: R. D. Manning, Jr., Dept. of Physiology
and Biophysics, University of Mississippi Medical Center, 2500 North
State St., Jackson, MS 39216-4505.
Received 1 October 1997; accepted in final form 25 March 1998.
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Am J Physiol Regul Integr Compar Physiol 275(1):R135-R140
0002-9513/98 $5.00
Copyright © 1998 the American Physiological Society
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Abstract
Introduction
![PS = PLF × (L/P)/[1 − (L/P)]](/content/vol275/issue1/fulltext/R135/img001.gif)
