Permeability of Connective Tissue Linings Isolated from Implanted
Capsules
IMPLICATIONS FOR INTERSTITIAL PRESSURE MEASUREMENTS
By Harris J. Granger and Aubrey E. Taylor
Downloaded from http://circres.ahajournals.org/ by guest on June 15, 2017
ABSTRACT
Quantification of the permeability of connective tissue linings isolated from implanted capsules was achieved by two types of experiments. The objective of the first
type was to determine the restriction offered by the lining to diffusion of l2:'I-labeled
human serum albumin. The restricted diffusion coefficient of albumin with respect to
the connective tissue lining the luminal capsule surface (internal lining) averaged 3.0 x
10~7 ± 0.4 x 10~7 cmVsec in ten experiments indicating that the rate of migration of
albumin across the structure was 35% of its free diffusion rate in water. In contrast, the
albumin diffusion coefficient obtained for the abluminal (external) lining suggested that
diffusion of albumin through this structure was 73% of the free diffusion rate in water.
The objective of the second type of experiment was to determine solute reflection
coefficients for inulin, serum albumin, and y-globulin with respect to the internal and
external linings. For the internal lining, the reflection coefficients were: inulin 0.07,
albumin 0.23, and y-globulin 0.53. The external lining showed greater leakiness as
evidenced by its lower reflection coefficient for a given molecule and its higher
hydraulic conductivity. An equivalent pore calculation resulted in a calculated pore
radius of 250-350 A for the internal lining and a calculated pore radius of 500-600 A for
the external lining. The ineffectiveness of the leaky capsule lining in transmitting
oncotic pressure suggests that under normal conditions the capsule measures interstitial hydrostatic pressure rather than oncotic pressure.
KEY WORDS
effective oncotic pressure
intracapsular pressure
dogs
• Because of the inaccessibility of the minute
interstitial spaces, interstitial fluid pressure has
been notoriously difficult to measure in a direct
manner. It is therefore not surprising that many
indirect techniques have been developed in an
attempt to gain access to the forces operating in
the interstitium. The subject of this paper is the
validity of one of these methods, namely, the
chronically implanted capsule technique of measuring interstitial fluid pressure.
In principle, the chronically implanted, perforated capsule provides a large artificial fluid space
in the tissue which is assumed to be in complete
equilibrium with surrounding interstitial fluid (1,
2). After subcutaneous implantation, fibrous connective tissue grows through the perforations and
lines the inner surface of the capsule, leaving a
From the Department of Physiology and Biophysics, University of Mississippi School of Medicine, Jackson, Mississippi 39216.
This work was supported by U. S. Public Health Service
Grants He-11678 and HE-11477 from the National Heart and
Lung Institute and Grant-in-Aid AHA 72-947 from the
American Heart Association.
Received March 21, 1974. Accepted for publication October
18, 1974.
222
reflection coefficients
diffusion coefficients
large fluid cavity in the center. A needle can then
be pushed through the skin, through one of the
perforations on the surface of the capsule, and
finally into the center of the capsule where the
fluid within the needle comes in intimate contact
with the intracapsular fluid. In contrast to the
positive pressures obtained by other investigators
using older methods, the pressure measured by the
perforated capsule technique is normally subatmospheric in subcutaneous tissue and several
other tissues of the body (1, 2).
The idea of free communication of protein between the capsular fluid and the fluid in the
surrounding interstitium has been challenged (3,
4). In essence, the argument has been put forth
that because the capsule is impermeable to proteins it behaves as an osmometer and, therefore,
measures the sum of oncotic and hydrostatic pressures (3). Support for this argument derives from
the finding that intracapsular pressure changes
when the capsular fluid is replaced by fluids with
various oncotic activities (4). That is, when high
concentrations of albumin are placed in the capsule, the capsular pressure increases. When solutions of very low oncotic activity are used, the
capsular pressure becomes more negative. This fact
Circulation Research, Vol. 36, January 1975
NEGATIVE INTERSTITIAL PRESSURE
Downloaded from http://circres.ahajournals.org/ by guest on June 15, 2017
suggests that the capsular membrane is highly
sensitive to oncotic pressure differences, as would
be expected if the fibrous lining greatly impeded or
actually prevented the movement of protein across
its structure.
We are therefore faced with two seemingly irreconcilable views on the nature of the intracapsular
pressure, one insisting that the capsule technique
measures interstitial hydrostatic pressure only (1,
2) and the other claiming that the capsule measures a combination of hydrostatic and oncotic pressures and is highly sensitive to protein osmotic
gradients (3, 4). Yet, neither of the proponents of
these current views has provided the prerequisite
quantitative assessment of the membrane properties of the fibrous lining necessary for resolution of
the conflict. Therefore, we performed an extensive
analysis of the permeability of fibrous linings
isolated from chronically implanted capsules. Utilizing the permeability data, we then computed the
possible contribution of transmural protein gradients to intracapsular pressure under various
conditions.
Methods
Perforated plastic hemispheres were implanted in the
limb subcutaneous tissue of ten dogs anesthetized with
sodium pentobarbital (30 mg/kg, iv). Then, 4-6 weeks
later, a needle connected to a P23Db pressure transducer was pushed through the skin, through one of the
capsule perforations, and finally into the central fluid
cavity of the hemisphere. After recording the intracapsular hydrostatic pressure, a small sample of capsular
fluid was withdrawn and the oncotic pressure measured
with a Prather-Hansen osmometer (5) fitted with an
Amicon PM-30 membrane. The hemisphere and surrounding tissue were then surgically removed, and the
baseplate was separated from the dome of the capsule.
The fibrous lining stripped from the luminal surface of
the baseplate was designated the internal lining; the
fibrous tissue isolated from the abluminal surface was
designated the external lining.
Quantification of the permeability of the fibrous
lining was achieved by two types of experiments. The
objective of the first type was to determine the restriction offered by the lining to diffusion of l25I-labeled
human serum albumin. To achieve this goal, the fibrous tissue slab was inserted between two chambers of
a modified Ussing transport apparatus (6). The two
chambers were filled with Tyrode's solution containing
an additional 100 mg/100 ml of glucose, and the solution was maintained at 37°C by a constant-temperature
circulation system which perfused a heat-exchange
jacket surrounding the transport apparatus. Radioiodinated albumin (Albumotope, Squibb) was then added to
one chamber, and the change in I25I radioactivity in
both chambers was determined every 15 minutes, utilizing a solid scintillation counter (Nuclear-Chicago
model 132B). A 5% CO2-95% O2 gas mixture was
bubbled through the two chambers to ensure adequate
Circulation Research, Vol. 36, January 1975
223
mixing. The restricted diffusion coefficient (DR) was
calculated from the unidirectional 123I-labeled albumin
flux (J), the thickness of the lining (AX), and the
radioactivity of the hot chamber (C,,). Since
J = DR • (C,,/AX),
DH = J- (AXVC,,).
To ensure the existence of a steady state or a quasisteady state, fluxes were calculated only after the rate
of activity increase in the cold chamber essentially
equaled the rate of decrease in the hot chamber. The
time required to achieve this steady-state condition
varied between 1 and 3 hours depending on the membrane thickness. Moreover, the flux from the hot side to
the cold side was measured during the early steadystate phase to obviate any error due to significant back
diffusion of tracer. In addition, by removing the slowly
accumulating '-"'I-labeled albumin from the sink chamber, it was possible to make consecutive diffusion coefficient determinations. In three experiments, diffusion
coefficients determined 18 hours after isolation of the
lining were not significantly different from the initial
determinations, indicating stability of lining structural
integrity under the conditions of the experiments.
In the second type of experiment, the effectiveness of
the fibrous lining as an osmotic membrane was analyzed by applying the theory of irreversible thermodynamics to membrane processes. According to Kedem and
Katchalsky (7), the volume or convective flow («/,.)
across a membrane is dependent on both the hydrostatic pressure difference (AP) and the Van't Hoff osmotic pressure difference (ATT) existing across the structure. Thus,
Jy = LP • A P + LPI) • An,
CHAMBER 1
CHAMBER 2
Jy = (_p £} P + !_pr\ ' tiTT
, Jv ,
tig-""
KV = L P
AX
FIGURE 1
Apparatus and equations used to determine hydraulic conductance (L,.J, osmotic conductance (h,.^, solute reflection
coefficient (a), and hydraulic conductivity (KVJ of capsule
linings. See text for definition of other abbreviations.
224
Downloaded from http://circres.ahajournals.org/ by guest on June 15, 2017
where LP is the hydraulic conductance relating the
volume flow to the hydrostatic pressure difference and
LPD is the osmotic conductance relating the convective
flow to an osmotic gradient. The ratio of osmotic conductance to hydraulic conductance (—LPD/LP) yields the
reflection coefficient (a), an important parameter of
membrane permeability. If the solute cannot penetrate
the membrane, the volume flow for a given osmotic
gradient is identical to the flow induced by a hydrostatic gradient of the same magnitude (LPn = LP). For
such a truly semipermeable membrane, the solute molecules are totally reflected from the membrane surface
after kinetic bombardment and the reflection coefficient
is 1. If, on the other hand, the membrane offers no
hindrance to solute migration, then none of the solute
molecules are reflected by the structure of the membrane and therefore the reflection coefficient is 0. In the
case of such an infinitely porous structure, no volume
flow can be induced by an oncotic gradient no matter
how large the potential difference (i.e.,LPI) = 0).
An alternate approach to the conceptual nature of the
reflection coefficient lies in considering the effect of
various degrees of permeability on the transmission of
osmotic forces across a membrane. For an ideal semipermeable membrane (cr = 1) the total Van't Hoff
osmotic potential is transmitted across the structure
when this membrane is mounted on an osmometer. In
contrast, only a fraction of the possible osmotic potential is transmitted if the membrane is permeable (a <
1) to the solute in question. Mathematically, the transmitted or effective osmotic pressure (ireff) is given by
neff = emit is this effective osmotic potential that must be
considered in any analysis of the effect of oncotic
gradients on intracapsular pressure.
The reflection coefficients of inulin, bovine serum
albumin (Cohn fraction V), and bovine -y-globulin (Cohn
fraction II) with respect to the inner and outer capsule
linings were determined utilizing the apparatus shown
in Figure 1. The following procedure was used. After
mounting the membrane in the apparatus, the two
chambers were filled with the bathing fluid described
earlier in this section. The hydraulic conductance was
then determined by measuring the rate of movement of
fluid through the calibrated micropipette extending
from chamber 1. The driving hydrostatic pressure difference was achieved by setting the height of the fluid
in the chamber 2 extension. After determining the
hydraulic conductance, the hydrostatic pressure difference was set to zero, the fluid in chamber 2 was
replaced by a solution containing the osmotic probe
species, and the osmotic conductance was obtained. The
reflection coefficients were then calculated from the
hydraulic and osmotic conductances. In addition, the
hydraulic conductivity (Kv) was calculated for each
membrane by multiplying the hydraulic conductance
and membrane thickness. At the end of the experiment
the hydraulic conductance was again determined to
check the possibility of tissue degeneration during the
course of the experiment. Since the second LP determination was nearly identical to the first, changes in fluid
channel dimensions due to swelling or degeneration
were not indicated.
To obtain a conceptual picture of the porosity of the
GRANGER, TAYLOR
fibrous lining, the equivalent pore model of Renkin (9)
was utilized to calculate the effective radius (r) of
cylindrical pores as a function of reflection coefficients,
solute radius (r8), and solvent (water) radius (/•„.). The
relationship between these variables is
1- a =-
Thus, by plotting 1 - a versus solute radius, a family of
curves can be generated, each curve representing a
certain equivalent radius. Superimposing experimental reflection coefficient data and literature values for
solute radii, a best-fit pore size or range of pore sizes
can be obtained.
All experimental results of this study are expressed
in terms of means ± SD.
Results
Intracapsular Hydrostatic and Oncotic Pressures.—The hydrostatic and oncotic pressures
measured in the 20 capsules used in this study
were -6.7 ± 1.7 mm Hg and 6.9 ± 1.9 mm Hg,
respectively. Although the average value of intracapsular hydrostatic pressure is nearly identical to
that obtained by other investigators (1, 2), the
oncotic pressure is higher than the 4-5-mm Hg
mean value previously reported (1). These higher
oncotic pressures suggest the possibility that the
range of effectiveness of interstitial oncotic pressure changes in prevention of gross fluid accumulation in the interstitium may be greater than
previously thought. This possibility has recently
been emphasized by Wiederhielm (3).
Rate of Diffusion of Albumin through the Capsule Lining.—The diffusion coefficient of albumin
with respect to the internal connective tissue lining averaged 3.0 x 10~7 ± 0.4 x 10"7 cnvVsec in
ten experiments. Assuming a diffusion coefficient
of 8.5 x 10~7 cm2/sec for movement of albumin in
water at 37°C (9), our data show that the capsule
lining is indeed highly permeable to this protein
molecule. However, the connective tissue lining
does offer enough hindrance to reduce the rate of
migration of albumin to 35% of its free diffusion in
pure water. In contrast, the diffusion coefficient
obtained for the external lining was 6.1 x 10"7 ±
0.7 x 10~7 cnvVsec in ten experiments, suggesting
that albumin diffusion through this barrier is
nearly 73% of the free diffusion rate in water.
Degree of Semipermeability of the Capsule Lining.—An example of the experiments designed to
quantify and compare the relative effects of hydrostatic and osmotic forces of equal magnitude on
fluid movement across the capsule lining is illustrated in Figure 2. In the absence of an oncotic
Circulation Research, Vol. 36. January 1975
NEGATIVE INTERSTITIAL PRESSURE
225
pressure difference across the internal lining, a
hydrostatic pressure difference of 15 mm Hg induced a volume flow of 0.23 /iliters/min. When the
same membrane was exposed on one side to a yglobulin concentration sufficient to generate 15
mm Hg of osmotic pressure in an osmometer, the
rate of flow was only 55% of that produced by the
hydrostatic pressure difference of the same magnitude. When albumin was used to induce a convective flow of water, the rate of fluid movement was
only 2Wc of the hydrostatic pressure-induced flow.
Inulin induced even less flow.
This type of experiment demonstrates that the
capsule lining does not behave as a true semipermeable membrane for molecules the size of y-
inulin
albumin
i—globulin
1.00.9Pore radius
0.8-
~ 700 A
\
0.7-
- 500 A
0.6-
s.
o
350 A
" 300 A
0.5-
X
0.4-
AP = I5
250 A
Downloaded from http://circres.ahajournals.org/ by guest on June 15, 2017
^ 200 A
0.30.20.10-
0
•
i
i
10 20
30 40
50 60
MOLECULAR RADIUS ( A )
FIGURE 3
Equivalent pore radius of internal and external capsule linings. Note that the equivalent pore radius of the external
lining (open circles) is larger than that of the internal lining
(solid circles). Each point represents the mean ± SD.
20
40
60
TIME (minutes)
FIGURE 2
Typical experiment showing the relative effects of hydrostatic
versus osmotic pressure differences of equal magnitude on
volume flow across the internal capsule lining. Note that
osmotically induced flow (1) is less than hydrostatically
induced flow for all three of the solute molecules studied and
(2) decreases with decreasing solute size (i.e., y-globulin >
albumin > inulin). Hydraulic conductance obtained at the
end of the experiment (solid circles) was not different from
that determined at the beginning of the experiment (open
circles), indicating the absence of significant tissue deterioration or swelling.
Circulation Research, Vol. 36, January 1975
globulin or smaller. The degree of semipermeability of the inner and outer capsule linings measured
in terms of the reflection coefficient is a function of
the molecular radius of the solute (Table 1). Thus,
for the internal membrane, the reflection coefficient is 0.53 ± 0.06 for -y-globulin, 0.23 ± 0.05 for
serum albumin, and 0.07 ± 0.02 for inulin. The
external lining showed a greater leakiness as evidenced by the lower reflection coefficient for a
given molecule and the higher hydraulic conductivity. Subjecting these data to an equivalent pore
model computation results in a calculated pore
radius of 250-350 A for the internal lining (Fig. 3,
solid circles) and a pore radius of 500-600 A for the
external lining (Fig. 3, open circles).
Discussion
The purpose of this study was threefold; (1) to
directly determine whether the connective tissue
lining of the subcutaneously implanted capsule is
permeable to serum proteins, (2) to quantify the
sensitivity of the lining to oncotic gradients, and
226
GRANGER, TAYLOR
TABLE 1
Membrane Parameters for Capsule Linings
Lpi, x 10'
(cm/sec mm Hg"1)
7
J-jp
v 11 U(V
X.
(cm/sec
mm Hg"1)
Downloaded from http://circres.ahajournals.org/ by guest on June 15, 2017
2.5
2.0
3.0
7.6
1.2
2.5
2.0
4.0
1.7
2.0
MEAN ± SD
IC
t\y
v
A
a — —LfuILp
1fV
±U
(crrrVsec
mm Hg"1)
2.5
3.0
2.7
3.8
1.3
3.0
3.0
4.0
1.7
2.8
Inulin
0.21
0.76
1.5
0.28
0.10
Albumin
•y-Globulin
Internal Lining
1.35
0.60
0.40
0.96
0.45
1.20
1.52
3.80
0.74
0.40
0.53
1.38
0.54
1.14
0.80
2.00
1.02
0.48
0.50
1.06
2.8 ± 0.8
Inulin
0.07
0.10
0.06
0.07
0.05
0.07 ± 0.02
Albumin
y-Globulin
0.24
0.20
0.15
0.20
0.33
0.21
0.27
0.20
0.28
0.25
0.23 ± 0.05
0.54
0.48
0.40
0.50
0.62
0.55
0.57
0.50
0.60
0.53
0.53 ± 0.06
0.15
0.13
0.20
0.11
0.10
0.14 ± 0.04
0.26
0.22
0.29
0.18
0.20
0.23 ± 0.04
External Lining
16
22
15
12.6
27
MEAN ± SD
15
22
17
13
27
2.4
2.9
3.0
1.4
2.7
18.8 ± 5.7
4.2
4.8
4.4
2.2
5.4
L,, = hydraulic conductance, LPD = osmotic conductance, Kv = hydraulic conductivity, and a = reflection coefficient.
(3) utilizing these data, to predict the possible
contribution of interstitial oncotic pressure to
measured intracapsular hydrostatic pressure under
equilibrium and nonequilibrium conditions.
Permeability of Capsule Lining and Its Sensitivity to Oncotic Gradients.—Our diffusion data
clearly demonstrate the permeability of the capsule lining to serum albumin. Although the diffusion coefficients do indicate a leaky membrane,
they do not provide any clue as to the effectiveness
of the lining as an osmometer membrane. For
example, it is a well-known fact that the capillary
membrane is leaky for albumin, yet the capillary
wall functions with 90-95% effectiveness in transmitting oncotic pressures under steady-state conditions (9). In other words, although the capillary
leaks protein, it possesses a high reflection coefficient for these molecules. Clearly, this is not the
case for the leaky capsule lining. In contrast to the
capillary membrane, the connective tissue which
lines the perforated capsule is only 25% effective in
transmitting oncotic forces in the case of albumin.
Even for the large -y-globulin molecule, the response to oncotic gradients is no more than 50% of
that theoretically expected for a true semipermeable membrane. In vivo support for these low reflection coefficients is provided by the exchange experiments reported by Stromberg and Wiederhielm
(4). In their study, elevating the intracapsular
albumin concentration from 2 g/100 ml to 7 g/100
ml resulted in only a 3-4-mm Hg increase in
intracapsular pressure. However, if the capsule
lining were impermeable to albumin, this 5 g/100
ml increase in albumin concentration would have
induced at least a 20-mm Hg increase in intracapsular pressure. Therefore, the data of Stromberg
and Wiederhielm (4) suggest a reflection coefficient
of 0.2 or less.
Oncotic Contribution to Intracapsular Pressure in
Equilibrium and Nonequilibrium States.—In light
of our data indicating low reflection coefficients for
albumin and y-globulin, what influence will interstitial oncotic pressure have on the intracapsular
pressure? If an oncotic contribution to intracapsular pressure exists under certain conditions, then
obviously in those cases intracapsular pressure is
not a measure of interstitial hydrostatic pressure
per se, but rather it reflects the sum of hydrostatic
and oncotic forces. To better understand the possible effects of oncotic pressure on intracapsular
pressure under all conditions, we must consider the
predicted behavior of the capsule in equilibrium
and nonequilibrium states.
A true semipermeable membrane (o- = 1) can
maintain an oncotic differential in the equilibrium
state, as exemplified by an osmometer. In contrast,
Circulation Research, Vol. 36, January 1975
227
NEGATIVE INTERSTITIAL PRESSURE
Downloaded from http://circres.ahajournals.org/ by guest on June 15, 2017
a leaky membrane (a < 1) such as the capsule
lining cannot maintain a protein osmotic difference
unless energy is provided to prevent equalization
of protein activities on the two sides of the
lining. In the absence of imparted energy, the
transmural protein activities will equilibrate across
the leaky membrane. Therefore, in the equilibrium
state, intracapsular oncotic pressure and interstitial oncotic pressure are identical, thus forcing
equality of intracapsular hydrostatic pressure and
surrounding interstitial hydrostatic pressure. The
existence of oncotic equilibrium between capsular
fluid and interstitium under normal conditions is
supported by the study of Taylor et al. (10) which
showed that subcutaneous capsular and lymphatic
125
I-labeled albumin activities are similar 130
hours after the radioactive protein is injected intravenously, and that in the normal subcutaneous
tissue of the limb and paw the albumin concentration, globulin concentration, and albumin-globulin
ratio are nearly identical for capsule fluid and
lymph. Thus, this study suggests that intracapsular pressure is equal to interstitial hydrostatic
pressure in normal, unperturbed subcutaneous tissue, since no protein gradient between capsule
fluid and lymph is demonstrable.
Suppose, on the other hand, there existed an
energy-dissipating mechanism for extruding protein from the capsule fluid into the interstitial
protein pool at a rate equal to its diffusion into the
capsule lumen. Then a continuous nonequilibrium
or steady-state situation would prevail and interstitial oncotic pressure could be maintained higher
than intracapsular oncotic pressure. If such a situation existed, true interstitial pressure could be
atmospheric while intracapsular pressure was negative. In other words, the negative intracapsular
pressure would simply reflect a protein osmotic
force imbalance across the capsule lining. In essence, this view is supported by Wiederhielm (11),
although he suggests convective streaming
through the capsule lining to maintain the interstitium-to-capsule protein gradient. However, a
simple calculation of the magnitude of interstitial
oncotic pressure required to produce an intracapsular pressure of - 7 mm Hg argues strongly against
such a mechanism.
The effective oncotic gradient generated by a
leaky membrane system is equal to a (n, - nc)
where TT, and nr are interstitial and capsule oncotic pressures, respectively, as measured with a
true semipermeable osmometer. Utilizing the experimentally determined reflection coefficient
(0.25) and capsule fluid oncotic pressure (5-7 mm
Hg), then to induce an effective oncotic gradient of
Circulation Research, Vol. 36, January 1975
7 mm Hg the aforementioned gradient-generating
mechanisms must maintain a steady-state interstitial osmotic pressure of more than 30 mm Hg.
Obviously, this value is unacceptably high in view
of the fact that plasma oncotic pressure in dogs is
normally only 20-22 mm Hg. Furthermore, as
noted previously, comparison of lymph and capsule
protein concentrations shows no significant oncotic
differences across the capsule lining. With these
arguments in mind, we think it unlikely that
oncotic pressure contributes to intracapsular pressure under normal, unperturbed conditions in subcutaneous tissue.
Although the leaky capsule appears to be in true
equilibrium with the interstitial space under normal conditions, this condition may not prevail
during the transients which occur as the interstitium moves from one equilibrium state to another.
For example, during rapid intravenous infusion of
saline, the interstitial oncotic activity may fall
fairly rapidly, but the decrease in intracapsular
oncotic pressure may be delayed because of the
small surface-volume ratio of the capsule and the
significant impediment offered by the lining to
diffusion of proteins. Although the capsule fluid
will finally equilibrate with the surrounding interstitium, an oncotic pressure contribution equal to
O-(T7> - TTC) will obtain during the transient; therefore, in terms of true interstitial fluid pressure, the
capsule technique will yield values which are in
error by CT(TT - nc) mm Hg. For subcutaneous
tissue, this error during transients will probably be
small, since the reflection coefficient and the normal interstitial oncotic pressure are both low. For
example, the transient error is less than 1.6 mm
Hg if interstitial oncotic pressure is suddenly reduced to zero, a most extreme condition. Rapid
infusion of Tyrode's solution usually reduces lymphatic oncotic pressure to low levels only after
gross interstitial edema occurs and intracapsular
pressure is elevated to +4—6 mm Hg. Assuming a
normal intracapsular pressure of —7 mm Hg, the
contribution of an oncotic gradient to the change in
capsular pressure is less than 15%. However, in
tissues characterized by a very high interstitial
oncotic pressure such as lung, liver, and intestine,
the significance of this error during transients will
increase.
References
1. GUYTON AC: Concept of negative interstitial pressure
based on pressures in implanted perforated capsules.
Circ Res 12:399-414, 1963
2. GUYTON AC, GRANGER HJ, TAYLOR AE: Interstitial fluid
pressure. Physiol Rev 51:527-563, 1971
228
GRANGER, TAYLOR
3. WIEDERHIELM CA: Dynamics of transcapillary fluid exchange. J Gen Physiol 52:29-63, 1968
through porous cellulose membranes. J Gen Physiol
38:225-243, 1954
4. STROMBERG DD, WIEDERHIELM CA: Effects of oncotic
9. LANDIS EM, PAPPENHEIMER JR: Exchange of substances
gradients and enzymes on negative pressures in implanted capsules. Am J Physiol 219:928-932, 1970
through the capillary walls. In Handbook of Physiology, Circulation, sec 2, vol 3, edited by WF Hamilton
and P Dow. Washington, D. C, American Physiological Society, 1963, pp 961-1034
5. PRATHER JW, GAAR KA JR, GUYTON AC: Direct continu-
ous recording of plasma colloidal osmotic pressure of
whole blood. J Appl Physiol 24:602-605, 1968
6. SCHULTZ SG, ZALUSKY R: Ion transport in isolated rabbit
ileum: I. Short circuit current and sodium fluxes. J
Gen Physiol 47:567-584, 1964
7. KEDEM O, KATCHALSKY A: Thermodynamic analysis of
the permeability of biological membranes to non-electrolytes. Biochim Biophys Acta 27:229-246, 1958
8. RENKIN EM: Filtration, diffusion and molecular sieving
10. TAYLOR AE, GIBSON WH, GRANGER HJ, GUYTON AC:
Interaction between intracapillary and tissue forces in
the overall regulation of interstitial fluid volume.
Lymphology 6:192-200, 1973
11. WIEDERHIELM CA: Interstitial space. In Biomechanics:
Its Foundations and Objectives, edited by YC Fung, N
Perone, and M Anliker. Englewood Cliffs, New Jersey,
Prentice-Hall, 1972, pp 273-286
Downloaded from http://circres.ahajournals.org/ by guest on June 15, 2017
Circulation Research, Vol. 36, January 1975
Permeability of connective tissue linings isolated from implanted capsules; implications for
interstitial pressure measurements.
H J Granger and A E Taylor
Downloaded from http://circres.ahajournals.org/ by guest on June 15, 2017
Circ Res. 1975;36:222-228
doi: 10.1161/01.RES.36.1.222
Circulation Research is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1975 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7330. Online ISSN: 1524-4571
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://circres.ahajournals.org/content/36/1/222
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in
Circulation Research can be obtained via RightsLink, a service of the Copyright Clearance Center, not the
Editorial Office. Once the online version of the published article for which permission is being requested is
located, click Request Permissions in the middle column of the Web page under Services. Further information
about this process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Circulation Research is online at:
http://circres.ahajournals.org//subscriptions/