Protein Content in Lymph and Edema Fluids in

Congestive Heart Failure

By CHARLES L. WITTE, M.D., MARLYS HEARST WIrrE, M.D.,
ALLAN E. DUMONT, M.D., WILLIAM R. COLE, M.D.,
AND JOHN R. SMITH, M.D.

SUMMARY
Protein content of tissue fluid and lymph is not uniform and depends upon regional
differences in capillary permeability modified by changes in capillary filtration pressure.
Whereas increased pressure in freely permeable liver sinusoids promotes formation of
excess liver and thoracic duct lymph and ascitic fluid high in protein, increased venous
pressure in less permeable beds promotes formation of excess lymph and edema fluid
Downloaded from http://circ.ahajournals.org/ by guest on April 6, 2017

progressively lower in protein content. To ascertain the influence of colloid osmotic

(oncotic) and hydrostatic pressure on excess lymph and edema formation in congestive
heart failure, a disorder characterized by generalized venous hypertension, protein
content of lymph (thoracic duct, liver, and small intestine), intracavitary and
peripheral edema fluid, and plasma were measured in 42 patients with cardiac failure.
In "acute" heart failure, thoracic duct lymph and ascitic fluid have high protein content
(85% and 68% of plasma protein respectively) and are derived primarily from the liver,
but in "chronic" heart failure protein content of thoracic duct lymph and ascitic fluid
are lowered (46% and 40% of plasma protein respectively) by lymph from extrahepatic
sites. In both stages, pleural and leg edema fluid are comparatively low in protein
content (26 to 44% and 3 to 8% of plasma protein respectively).
In congestive heart failure, edema and intracavitary fluid form primarily in response
to increased venous pressure which outside t-he liver is partially counterbalanced by
increased effective plasma oncotic pressure.

Additional Indexing Words:

Ascites Pleural effusion Heart failure Protein Oncotic pressure

T HE PARTITION of extracellular fluid to the blood stream.3 However, the amount

between blood and tissues is determined
primarily by the balance of hydrostatic and
oncotic pressure gradients across capillary
membranes.' 2 A small excess of tissue fluid
normally forms, enters lymphatics, and returns
From the Departments of Surgery and Medicine
(Cardiology Division), Washington University Schobl
of Medicine, St. Louis, Missouri, and Department of
Surgery, New York University School of Medicine,
New York.
Supported by grants (HE 09073, 11034, 11904,
12179, and AM 10875) from the U. S. Public Health
Service, the American and Missouri Heart Associa-
tions, and the Institute of Medical Education and
Research, City Hospital, St. Louis, Missouri.
Dr. M. Witte is an Established Investigator of the
Circulation, Volume XL, November 1969
and composition of excess tissue fluid or
lymph is not uniform throughout the body4 5
and depends not only on "Starling forces" but
also on regional differences in capillary
permeability.6 Thus, highly permeable hepatic
sinusoids produce a lymph that is almost as
high in protein content as plasma, whereas the
less permeable limb capillaries form lymph
that is low in protein.7 Furthermore, venous
hypertension that results from restriction to
American Heart Association. Dr. Dumont is a
recipient of the U. S. Public Health Service Career
Research Development Award.
Address for reprints: Dr. C. Witte, Department of
Surgery, University of Arizona, Tucson, Arizona 85721.
623
 624
venous blood flow not only increases filtration
pressure and formation of lymph, but further
exaggerates regional differences in protein
content of lymph.8'9 It is ultimately the
effective colloid osmotic (oncotic) pressure of
plasma (plasma minus tissue) that counter-
balances the effective filtration pressure.10
In congestive heart failure, venous return is
impeded and venous pressure and volume
increase. Accordingly, filtration of fluid out of
capillaries into tissues is favored and produc-
tion of lymph increases."1 12 Although the
complex derangements leading to edema
formation in this disorder are not clearly
understood, a satisfactory explanation must
Downloaded from http://circ.ahajournals.org/ by guest on April 6, 2017
encompass regional differences in capillary
fluid fluxes and in lymph drainage.
On the basis of these considerations, protein
content in lymph and edema fluids was
measured in patients with cardiac failure in an
attempt to determine the effective plasma
oncotic pressure and the influence of capillary
hydrostatic pressure on production of excess
interstitial fluid in congestive heart failure.
Total protein content of thoracic duct, liver
and intestinal lymph, peritoneal, pleural, and
peripheral edema fluid and plasma was
measured in various combinations in 42
patients with varying severity and duration of
cardiac decompensation. The results were
compared with findings in control subjects
and with previous observations in patients
with hepatic cirrhosis in whom venous hyper-
tension is confined to the splanchnic bed, a
great excess of thoracic duct lymph is formed,
and ascites is a common occurrence.
Table
List of Patients Studied with Congestive Heart Failure
No. of
Type of heart disease patients
Arteriosclerotic 21
Rheumatic 10
Congenital 4 3
Cor pulmonale 4 3
Marie-Strumpel spondylitis 1 1
(aortic insufficiency)
Idiopathic cardiomyopathy 1 1
Unknown 1 0
Total 42
WITTE ET AL.
Methods
Forty-two patients with existing or prior
cardiac failure were studied (table 1). Each
patient was under treatment in the hospital or
had been treated for congestive heart failure
previously. Observations were made in 17 living
patients, including three with "compensated"
cardiac failure, and in 25 others at autopsy. The
etiology of cardiac failure varied but the
predominant causes were arteriosclerotic and
rheumatic heart disease. Ages ranged from 4
weeks to 88 years.
Eighteen patients who died within 3 weeks
after onset of symptoms were categorized as
"acute" cardiac failure. Each patient was receiv-
ing digitalis therapy, and 14 of them were being
treated with diuretic drugs at the time of death.
Twenty-one patients who had signs and
symptoms of cardiac decompensation for several
months to several years were classified as
"chronic" congestive heart failure. They had been
eating a salt-restricted diet and had been
receiving continuous medication, including digi-
talis and diuretic drugs. Thirteen patients had
central venous pressure determinations while in
cardiac failure; the mean value was 32 cm of
saline and the median 27 cm of saline. In 19 of the
patients the functional and therapeutic classica-
tion was IV-E.
Three patients had "compensated" heart fail-
ure. None had visible edema and functional-
therapeutic classification ranged from I-A to II-B.
Each patient was receiving digitalis and two were
receiving diuretic drugs as well.
Total protein content in lymph, ascitic, pleural
and peripheral edema fluid, and plasma was
measured in a T/S refractometer (Ameican
Optical Model 10401) or by the biuret method.
Small samples of lymph were collected in
heparinized capillary tubes after transection of a
lymphatic vessel. Peripheral edema fluid was
similarly collected spontaneously or during gentle
compression after insertion of a fine needle into
Sex Age in yeare (mean)
Male Female Male Female
10 11 68 75
3 7 42 49
1 11 47
1 59 45
0 51 --
0 45
1 - 47
21 21 46 53
Circlatsion, Volume XL, November 1969
 PROTEIN CONTENT IN LYMPH AND EDEMA FLUIDS 625
Plasma Protein 7.009 7.7!1.2 6.6t1.2 5.51.5
(Gm %) patients) and left (9 patients) thoracic cavities,
8316 ascitic fluid (22 patients), leg edema fluid (4
patients) and plasma (25 patients) were ob-
tained and total protein content was measured. In
78 samples the albumin level was determined by
Micro Zone electrophoresis (Beckman Model
R100, 110) or by salt fractionation. The findings
were compared with values in lymph and plasma
5- at operation or autopsy in control subjects without
Kq congestive heart failure or hepatic cirrhosis.
K12
Results
Figures 1 to 3 summarize the total protein
Figure 1
content (expressed as % plasma level) in
lymph and edema fluids in patients with
Total protein in thoracic duct lymph (mean + SD) in "acute," "chronic," and "compensated" conges-
control subjects and in patients with acute, chronic,
and compensated congestive heart failure (CHF). tive heart failure. Total protein levels in
Downloaded from http://circ.ahajournals.org/ by guest on April 6, 2017

Numbers at the bottom of each bar represent number lymph of control subjects are shown in figures
of patients studied. 1 and 2.

In patients with "acute" congestive heart

the edematous leg. In 15 patients the thoracic failure, the protein level in thoracic duct
duct in the left side of the neck was cannulated lymph was 15% higher than control values
under local anesthesia for therapeutic purposes, (P <0.01) and within normal limits in liver
and lymph flow rate (by gravity drainage) and and intestinal lymph* (figs. 1 and 2). The
total protein content were determined. These
cases were reported in detail previously.". 12 protein content in ascitic fluid was very high
In two of the patients leg edema fluid was (68% of plasma protein), lower in right and
sampled and total protein content determined. left pleural fluid (44% and 35% of plasma
In 25 patients at autopsy, samples of thoracic protein respectively), and very low in leg
duct lymph from the posterior mediastinum (16 edema fluid (3% of plasma protein; fig. 3).
patients), liver lymph from periportal lymphatics
(17 patients), intestinal lymph from mesenteric
lacteals (9 patients), pleural fluid from right (14
*No difference was found in control protein levels
Plasma Protein 6.8 t 1 3 7.8 '1.2 6.8t 09 in thoracic duct, liver, and intestinal lymph obtained
(Gm %)
06 t 11
at operation or at autopsy as reported previously.13
Lymph:
El Liver Plasma Protein 7.6 1.3 6.7 t 1.2
(Gm%)
E3 Intestinel Asclitec Fluid
0 Righit Pleural Fluid
Q Left Ploura/ Flid
* Leg Edema Fluad

40 ,19

29t 9

3I-1
Figure 2
Figure 3
Total protein in liver and intestinal lymph (mean + SD)
in control subjects and in patients with acute and Total protein in ascitic, pleural, and peripheral edema
chronic congestive heart failure (CHF). Numbers at fluid in acute and chronic congestive heart failure
the bottom of each bar represent number of patients (CHF). Numbers on the bottom of each bar represent
studied. number of patients studied.
Circulation, Volume XL, November 1969
 626 WITTE ET AL.
Table 2
Average Levels of Albumin (A) and Globulin (G) in Plasma and Lymph (G/100 ml) Based on the Total and
Fractional Protein Content in Patients with "Acute," "Chronic," and "Compensated" Congestive Heart Failure
(CHF) Compared with Control Subjects*
Control "Acute" CHF "Chronic" CHF "Compensated" CHF
Total Total Total Total
protein %A A/G protein %A A/G protein %A A/G protein %A A/G

Plasma 6.6 57.0 387

2.84
8.0 45.8 -36
4.3
6.5 48.4 3.1
3.36
5.8 59.0 334
23
(11) (10) (12) (2)
Thoracic duct lymph 4.3 59.0 2.70 7.1 43.8 3.0 3.0 46.9 1.38 4.0 68.8 25
(10) 1.0 (6) 4.00 (4) 1.62 (2) 1.25

Liver lymph 6.2 64.2 222 8.7 48.4 420 6.3 46.7
2.9

(2) 2.22 (4) 4.50 (3) 3.36

Intestinal lymph 4.1 62.3 2.55 5.2 45.8 2.39 3.0 40.7 1.76
Downloaded from http://circ.ahajournals.org/ by guest on April 6, 2017

(2) 1.55 (3) 2.81 (3) 17

* Numbers in parentheses represent the number of subjects whose data have been averaged for the value
tabulated.
Table 3
Average Levels of Albumin (A) and Globulin (G) in Ascitic, Pleural, and Leg Edema Fluid
(g/100 ml) Based on the Total and Fractional Protein Content in Patients with "Acute' and
"Chronic" Congestive Heart Failure (CHF)*
"Acute" CHF "Chronic" CHF
Total Total
protein %A A/G protein %A A/G

Ascitic fluid 5.7 48.7 2.78 2.8 46.3 1.30

(9) 2.92 (3) 1.50

Right pleural fluid 3.6 57.2 12.504 2.0 46.0 1.08

10
(4) 1.4(2)
Left pleural fluid 2.4 50.5 1.21 2.4 41.1 0.98
(4) 1.19 (2) 1.42

Leg edema fluid 0.3 58.0 0.17 0.6 47.5 0.28

(2) 0.3(3) 03

* Numbers in parentheses represent number of subjects whose data have been averaged for
the value tabulated.
In patients with "chronic" congestive heart
failure, the protein content in thoracic duct
lymph was 36% lower (P < 0.01) and in
intestinal lymph 31% lower (P <0.02) than
control values and within normal limits in
liver lymph (figs. 1 and 2). The protein
content in ascitic fluid and right pleural fluid
was 41% lower (P < 0.01 and P < 0.02 respec-
tively) than values in "acute" heart failure,
but the protein level in leg edema and left
pleural fluid was not significantly different
(P > 0.4 and P > 0.2 respectively) from val-
ues in "acute" heart failure (fig. 3).
In patients with "compensated" congestive
heart failure, the protein level in thoracic
duct lymph was within normal limits (fig. 1).
Tables 2 and 3 represent the average levels
of albumin and gobulin in plasma, lymOp,
and edema fluids in patients in congestive
heart failure as compared with control sub-
jects. The albumin fraction was lower in
patients with heart failure but there were no
Cisrclaiton, Volsme XL, November 1969
 PROTEIN CONTENT IN LYMPH AND EDEMA FLUIDS 627
Table 4
Estimated Oncotic Pressure (H in mm Hg) in Plasma (H P), Liver (HLL), Extrahepatic Portal (IL) and
Peripheral Tissues (He) in Control Patients and in Those with "Acute" and "Chronic" Congestive Heart Failure
(CHF) Calculated from Albumin and Globulin Concentrations (g%)* in Plasma, Liver Lymph, Intestinal
Lymph, and Peripheral Interstitial Fluid (Tables 2 and 3)
Effective IIP
Control "Acute" CHF "Chronic" CHF Control "Acute" CHF "Chronic" CHF
HP 19.6 23.6 18.3
IILL 19.1 26.4 17.4 Liver (HiP - ILL) +0.5 -2.8 +0.9
HlIL 11.4 13.6 7.1 Intestine (IIP - IL) +8.2 +10.0 +11.2
He 4.8t 0.7 0.8 Leg (iiP - He) +14.8 +22.9 +17.5
* Based on van't Hoff's law corrected for Donnan effects and protein-protein interaction'4
H albumin = 2.8c + 0.18c2 + 0.012c3
H globulin = 1.6c + 0.15c2 + 0.006c3
(c = g%).
t Estimated from animals. 15
Downloaded from http://circ.ahajournals.org/ by guest on April 6, 2017

essential differences between the "acute" and
"chronic" stages. Note that there is a slight
discrepancy between the average values in
total protein shown in figures 1 to 3 because
not all samples were fractionated for albumin.
Table 4 represents estimated oncotic pres-
sure in the plasma, liver, intestine, and lower
extremity in control patients and in those with
congestive heart failure. Whereas venous
hypertension in heart failure immediately
tends to shift fluid into the liver, an increase in
effective plasma oncotic pressure in extrahepa-
tic portal and peripheral capillaries requires a
rise of at least 4 mm Hg in filtration pressure
to produce a net fluid flux into these tissues.
Discussion
Starling recognized the importance of plas-
ma oncotic pressure in regulating capillary
fluid exchange; he reasoned further that
elevation of capillary hydrostatic pressure
would lead to a fall in tissue oncotic pressure:
"With increased capillary pressure there must
be increased transudation until equilibrium is
established at a somewhat higher point, when
there is a more dilute fluid in the tissue spaces
and therefore a higher absorbing force to
balance the increased capillary pressure."'
In general, mild elevations in venous
pressure are initially counterbalanced by a
reduction in tissue oncotic pressure (table 4),
but a further sustained rise in venous pressure
shifts fluid into tissues and increases flow of
Circulation, Volume XL, November 1969
low-protein lymph.3 16 When the rate of
formation of capillary filtrate exceeds the rate
of lymph reabsorption, low-protein edema
fluid accumulates.7' 17
The liver, however, does not behave in this
fashion. Hepatic sinusoids are perfused pri-
marily by low-pressure portal venous blood
and are lined by a very tenuous endothelium
with large gaps,'8 allowing molecules the size
of plasma protein to pass freely.6 18 As a
result, there is little or no oncotic gradient
across the sinusoidal wall. Small increments in
the normally low venous pressure produce a
great increase in production of hepatic capil-
lary filtrate and hepatic lymph high in
protein.'9 20 Accordingly, in dogs with con-
striction of the inferior vena cava above the
diaphragm and in patients with "early"
hepatic cirrhosis, restriction to hepatic venous
outflow greatly increases flow of high-protein
lymph from periportal hepatic lymphatics and
the thoracic duct.20 2' When transfer of fluid
out of the sinusoid exceeds the capacity of
hepatic lymphatics to absorb the fluid, excess
liver lymph spills into the peritoneal cavity to
form ascitic fluid high in protein.20 21 In
contrast, in dogs with an aorto-portal vein
shunt combined with restriction to transhepa-
tic portal blood flow, and in patients with far-
advanced hepatic cirrhosis, marked elevation
in extrahepatic portal pressure (>30 cm of
saline) promotes the formation of large
 628
amounts of both mesenteric and thoracic duct
lymph very low in protein.21'22 When transfer
of fluid out of splanchnic capillaries exceeds
the capacity of mesenteric lymphatics to
absorb the fluid, excess extrahepatic portal
lymph very low in protein accumulates in the
peritoneal cavity.21' 22
Failure of the heart to pump blood
effectively into the arterial circulation leads to
venous hypertension. The delicately balanced
liver sinusoid responds with a great outpour-
ing of liver lymph high in protein that floods
the thoracic duct. When the formation of
excess liver lymph is more rapid than its
reabsorption, ascitic fluid high in protein
accumulates. (As in caval-constricted dogs,
Downloaded from http://circ.ahajournals.org/ by guest on April 6, 2017
protein values in ascitic fluid are somewhat
lower than in liver lymph after osmotic
equilibration with interstitial fluid in the
extrahepatic portal bed).19 23 On the other
hand, venous hypertension outside the liver
increases filtration of water more than pro-
tein.24 When regional lymphatics are over-
whelmed, peripheral edema fluid very low in
protein and pleural fluid relatively low in
protein result.*
Starling believed that in the early stages of
heart failure forced outflow of plasma from
the venous side of the circulation into the liver
substance and its lymphatic network protected
the failing heart and at the same time buffered
the circulation outside the liver from venous
hypertension.27 The data suggest, however,
that as this compensatory mechanism becomes
insufficient, excess lymph can no longer return
to central veins with elevated pressure as fast
as it forms, and resistance to transhepatic
portal blood flow rises. Mesenteric venous
hypertension develops, and protein content in
extrahepatic portal lymph falls. Protein con-
centration of thoracic duct lymph also de-
creases, reflecting the greater contribution of
extrahepatic lymph. However, the protein
*In recumbent animals, protein content of leg
lymph is normally 20 to 30% of plasma level,15 and
protein content in pleural fluid in diseases not
characterized by venous hypertension (for example,
carcinoma and tuberculosis) is 60 to 80% of plasma
level.25. 26
WITTE ET AL.
levels in intestinal and thoracic duct lymph
and ascitic fluid seldom fall to the very low
levels characteristic of far-advanced hepatic
cirrhosis in which portal hypertension is much
more prominent. The difference in portal
circulatory dynamics between cirrhosis and
congestive heart failure probably relates to
concomitant alterations in splanchnic arterial
blood flow. Whereas patients with cirrhosis
have normal or increased cardiac output28 in
conjunction with reduced transhepatic portal
blood flow,29 patients with heart failure have
decreased effective cardiac output3' 31 partial-
ly offsetting the tendency for portal pressure
to rise from increased resistance to transhepa-
tic portal flow.
Controversy exists concerning the mecha-
nism of edema formation in congestive heart
failure-that is, does edema result primarily
from renal salt and water retention,3236
lymphatic obstruction,37 or changes in capil-
lary permeability due to decreased cardiac
output and hence arterial perfusion,31'37 or is
it a direct result of systemic venous hyperten-
sion?38 39 Ischemia or trauma to capillaries as
well as lymphatic obstruction alone results in
edema fluid that is consistently high rather
than low in protein.40'41 Plasma simply "leaks"
into tissues in bulk or fails to be removed.
Lymph stasis, however, does eventually devel-
op in cardiac failure as lymphatics are
overloaded and lymph flow into high pressure
central veins is impeded.445 But the fact
that ascitic fluid from the liver is high in
protein, and that edema fluid in other areas is
low indicates that the primary driving force is
venous hypertension resulting from failure of
forward venous flow. Retention of salt and
water further expands extracellular fluid vol-
ume and imposes an ever increasing burden
on an already overworkedb lymphatic circula-
tion. On the other hand, treatment with low-
salt diet and diuretic drugs contracts extracel-
lular fluid volume and reduces the load on the
lymphatic circulation.
In congestive heart failure, the protein
content of lymph and edema fluids reflects the
hydrostatic pressure in different capillary beds
and allows an estimation of effective plasma
Circulation, Volume XL, November 1969
 PROTEIN CONTENT IN LYMPH AND EDEMA FLUIDS
oncotic pressure, a crucial unknown in Star-
lings law of transcapillary fluid exchange.
High-protein ascitic fluid, relatively low-pro-
tein pleural fluid and very low protein
peripheral edema fluid arise primarily in
response to venous hypertension, which favors
capillary filtration and eventually impedes
lymphatic drainage.
References
1. STARLING, E. H.: On the absorption of fluids
from the connective tissue spaces. J Physiol
(London) 19: 312, 1896.
2. STARLING, E. H.: The Fluids of the Body.
Chicago, University of Chicago Press, 1909, p.
67.
3. WIEDERHIELM, C. A.: Dynamics of transcapil-
Downloaded from http://circ.ahajournals.org/ by guest on April 6, 2017
lary fluid exchange. In Biological Interfaces:
Flow and Exchanges. Proceedings of a
Symposium sponsored by the New York Heart
Association. Boston, Little, Brown and Co.,
1968, p. 29.
4. WOLF, A. V.: Volume and pressure imbalances in
the genesis of edema. In Edema: Mechanisms
and Management, edited by J. H. Moyer and
M. Fuchs. Philadelphia, W. B. Saunders Co.,
1960, p. 23.
5. STEAD, E. A., AND WARREN, J. V.: Protein content
of the extracellular fluid in normal subjects
after venous congestion and in patients with
cardiac failure, anoxemia and fever. J Clin
Invest 23: 283, 1944.
6. MAYERSON, H. S.: - Physiologic importance of
lymph. In Handbook of Physiology, Section 2,
Circulation, vol. 2, edited by W. F. Hamilton
and P. Dow. Washington, D. C., American
Physiologic Society, 1963, p. 1035.
7. STARLING, E. H.: Physiological factors involved
in the causation of dropsy. Lancet 1: 1267,
1896.
8. WmTm, J. C., FIELD, M. E., AND DINKER, C.
K.: On the protein content and normal flow of
lymph fromn the foot of the dog. Amer J
Physiol 103: 34, 1933.
9. LANDIS, E. M., JONES, L., ANGEVINE, M., AND
ERB, W.: Passage of fluid and protein through
the human capillary wall during venous
congestion. J Clin Invest 11: 717, 1932.
10. PAPPENHEIMER, J. R., AND SOTO-RIVERA, A.:
Effect of osmotic pressure on the plasma
protein and other quantities associated with the
capillary circulation in the hind limb of cats
and dogs. Amer J Physiol 152: 471, 1948.
11. DUMONT, A. E., CLAuss, R. H., REED, G. E., AND
TICE, D. A.: Lymph drainage in patients with
congestive heart failure. New Eng J Med 269:
949, 1963.
12. WITTE, M. H., DUMONT, A. E., CLAuss, R. H.,
Circulation, Volume XL, November 1969
629
RADER, BERTHA, LEVINE, NoRnMAN, AND BREED,
E. S.: Lymph circulation in congestive heart
failure: Effect of extemal thoracic duct
drainage. Circulation 39: 723, 1969.
13. WITTE, C. L., WITTE, M. H., COLE, W. R.,
CHUNG, Y. C., BLEISCH, V. R., AND DUMONT,
A. E.: Dual origin of ascites in hepatic
cirrhosis. Surg Gynec & Obstet. In press.
14. LANDIS, E. M., AND PAPPENHEIMER, J. R.:
Exchange of substances through the capillary
walls. In Handbook of Physiology, Section 2,
Circulation, vol. 2, edited by W. F. Hamilton
and P. Dow. Washington, American Physiolo-
gic Society, 1963, p. 961.
15. YOFFEY, J. M., AND COURTICE, F. C.: Lymphatics
and Lymphoid Tissue. Cambridge, Massachu-
setts, Harvard University Press, 1956, p. 238.
16. IBM, p. 86.
17. FAHR, G., AND ERSHLER, I.: Studies of the factors
concerned in edema formation: II. Hydrostatic
pressure in the capillaries during edema
formation in right heart failure. Ann Intern
Med 15: 798,1941.
18. BRAUER, R. W.: Liver circulation and function.
Physiol Rev 43: 115, 1963.
19. HYATT, R. E., LAURENCE, G. H., AND SMITH, J.
R.: Observations on the origin of ascites from
experimental hepatic congestion. J Lab Clin
Med 45: 274, 1955.
20. HYATT, R. E., AND SMITH, J. R.: Mechanisms of
ascites: Physiologic appraisal. Amer J Med
16: 434, 1954.
21. WITTE, C. L., WITTE, M. H., DUMONT, A. E.,
FRIST, J., AND COLE, W. R.: Lymph protein in
hepatic cirrhosis and experimental hepatic and
portal venous hypertension. Ann Surg 168:
567, 1968.
22. WITTE, C. L., CHuNG, Y. C., WrrrE, M. H.,
STERLE, 0. F., AND COLE, W. R.: Observations
on the origin of ascites from experimental
extrahepatic portal congestion. Ann Surg. In
press.
23. COURTICE, F. C., AND STEINBECK, A. W.:
Absorption of protein from the peritoneal
cavity. J Physiol (London) 114: 336, 1951.
24. RUSZNYAK, I., FOLDI, M., AND SzABo, G.:
Lymphatics and Lymph Circulation: Physiol-
ogy and Pathology, ed. 2. New York,
Pergamon Press, 1967, p. 20.
25. JAMES, A. H.: Mechanism of pleural and ascitic
effusions, with a suggested method for the
indirect estimation of portal venous pressure.
Clin Sci 8: 291, 1949.
26. LUETSCHER, J. A., JR.: Electrophoretic analysis of
the proteins of plasma and serous effusions. J
Clin Invest 20: 99, 1941.
27. STARLING, E. H.: Some points on the pathology
of heart disease (The Arris and Gale
Lectures). Lancet 1: 652, 1897.
 630
28. MURRAY, J. F., DAWSON, A. M., AND SHERLOCK,
S.: Circulatory changes in chronic liver disease.
Amer J Med 24: 358, 1958.
29. MORENO, A. H., BURCHELL, A. R., ROUSSELOT, L.
M., PANKE, W. F., SLAFSKY, S. F., AND BURKE,
J. H.: Portal blood flow in cirrhosis of the
liver. J Clin Invest 46: 436, 1967.
30. MERRILL, A. J.: Edema and decreased renal
blood flow in patients with chronic congestive
heart failure: Evidence of forward failure as
the primary cause of edema. J Clin Invest 25:
389, 1946.
31. BURCH, G. E., AND RAY, C. T.: Consideration of
the mechanism of congestive heart failure.
Amer Heart J 43: 918, 1951.
32. WARREN, J. V., AND STEAD, E. A., JR.: Fluid
dynamics in chronic congestive heart failure.
Arch Intern Med (Chicago) 73: 138, 1944.
33. STARR, I., JEFFERS, W. A., AND MEADE, R. H.,
Downloaded from http://circ.ahajournals.org/ by guest on April 6, 2017
JR.: Absence of conspicuous increments of
venous pressure after severe damage to the
right ventricle of the dog with a discussion of
the relation between chemical congestive
failure and heart disease. Amer Heart J 26:
291, 1943.
34. STARR, I.: Our changing viewpoint about
congestive failure. Ann Intern Med 30: 1,
1949.
35. ELKINTON, J. R., AND SQUIRES, R. D.: Distribu-
tion of body fluids in congestive heart failure.
Circulation 4: 679, 1961.
WITTE ET AL.
36. BRIGGS, A. P., FOWELL, D. M., HAMILTON, W.
F., REMINGTON, J. W., WHEELER, N. C., AND
WINSLOW, J. A.: Renal and circulatory factors
in the edema formation of congestive heart
failure. J Clin Invest 27: 810, 1948.
37. PAINE, R., AND SMITH, J. R.: Mechanism of
heart failure. Amer J Med 6: 84, 1949.
38. DAvis, J. O., AND SMITH, J. R.: Pathogenesis of
peripheral cardiac failure. Amer J Med 3: 704,
1947.
39. RAY, C. T., AND BURCH, G.: Vascular response in
man to ligation of the inferior vena cava. Arch
Intern Med (Chicago) 80: 587, 1947.
40. YOFFEY, J. M., AND COURTICE, F. C.: Lymphatics
and Lymphoid Tissue. op. cit. (ref. 24), p. 90.
41. IBID, p. 458.
42. FOLDI, M., AND PAPP, N.: Role of the lymph
circulation in congestive heart failure. Jap Circ
J 25: 703, 1961.
43. WEGRIA, R., ET AL.: Effect of systemic venous
pressure on drainage of lymph from thoracic
duct. Amer J Physiol 204: 284, 1963.
44. SZABO, G., AND MAGYAR, Z.: Effect of increased
systemic venous pressure on lymph pressure
and flow. Amer J Physiol 212: 1469, 1967.
45. MCMASTER, P. D.: Lymphatics and lymph flow
in the edematous skin of human beings with
cardiac and renal disease. J Exp Med 65: 373,
1937.
Circulation, Volume XL, November 1969
 Protein Content in Lymph and Edema Fluids in Congestive Heart Failure
CHARLES L. WITTE, MARLYS HEARST WITTE, ALLAN E. DUMONT,
WILLIAM R. COLE and JOHN R. SMITH
Downloaded from http://circ.ahajournals.org/ by guest on April 6, 2017

Circulation. 1969;40:623-630
doi: 10.1161/01.CIR.40.5.623
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright 1969 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://circ.ahajournals.org/content/40/5/623

Permissions: Requests for permissions to reproduce figures, tables, or portions of articles

originally published in Circulation 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 is online at:

http://circ.ahajournals.org//subscriptions/