creased renal vein pressures result-
tural or: body positional changes
heart failure (7).-
indicate that at normal renal
renal Vein pressure may be
‘éonsiderably high: levels before
lynamic renal alterations occur.
‘position or posture. would
ell in this instance with no
‘the kidney due’ to venous
Serious difficulties may

‘Fenal arterial vasoconstriction
ather: small changes in renal
in these latter instances,

lave detrimental or depressant
‘hemodynamics and function.

R. P. Keating and H. P.
57: 1, 1949.

3.
4.

5.

6.

10.

il.

. Hinshaw, L, B., A. D. Flai

Haddy, F, J., Circulation Res. 4: 659, 1956,

Gctevaalt B, Pflugers Arch. ges Physiol. 262: 207,
Waugh, W, H. and W. F. Hamilton. Circulation Res.
5: 116, 1958,

Haddy, F, J., J. Scott, M. Fleishman and D. Emanuel.
Am. J. Phi doe 19s 97, 1958.

Smith, Homer W. The Kidney. Oxford University
Press, New York, 1951.

Semple, S, J. CG, and H. E. de Wardener. Circulation
Res. 7: Gis! 1959.

R. L. Logemann and
C. HL Carlson, Am. J. Physiol. 198: 891, 1960.

Hinshaw, L, B, and D. M. Worthen. Circulation Res.
9: 1156, 1961,

Hinshaw, L. B., G. M.
Am. J. Physiol, 196: 1127, 1959.

and C. H. Carlson.

Worthen, D, M., Q. N. Anderson and L. B. Hinshow.
Am. J. Physiol, 202: 97, 1982.

13. Hinshaw, L. B., S. B. Day and C. H. Carlson. Am. J.

4

-12-—

Physiol. 197; 309, 1959.
Winton, F. R, Physiol. Revs. 17: 408, 1937.


fall as renal vein pressure is increased, while
pre-venous resistance (R,.:) remains relatively
constant. It is clearly seen that the cause of
the decrease in R, is the drop in R, segment
resistance,

Figure 2 represents an experiment on another
isolated perfused kidney when renal artery
pressure is maintained at a lower value (108-
110 mm, Hg) than in Figure 1, in which con-
trol IRVP and TP values are also less than those
in Figure 1. Results are consistent with those
in Figure 1, except that renal blood flow and
urine flow decrease at lower renal vein pressure
values, When RVP is increased, renal blood
flow does uot show a significant drop until
RVP exceeds 25-35 mm. Hg, which approxi-
mates the control (zero time) IRVP and TP.
Above this pressure RVP, IRVP and TP rise in
an approximate 1:1 fashion. Again, a progres-
sive decrease in R, is observed as a function of
an increase in RVP, which is due to a fall in
R, segment resistance. When RVP is returned
to zero mm. Hg, there is a good recovery of all

‘parameters to conttol values in experiments

shown in Figs. 1 and 2.

Figure 3 illustrates mean values for sixteen
separate renal perfusions. Individual experi-
ments followed courses similar to those shown
in Fig. 1 and 2. The maximal increase in RVP
in which there was no significant change in
renal blood flow is indicated in the figure and
averaged 38 mm. Hg (‘S. E. = 4). Mean values
of measured and calculated parameters for the
sixteen experiments are also shown in the
figures, Renal artéry pressure was maintdined
constant in each experiment by mi of a
Starling shunt device (average arterial ure,
131 mm. Hg, S. E. + 5). As RVP was in-
creased to a mean value of 38 mm. Hg, there
were no significant changes in blood aud urine

IRVP and TP. Decreases in R, and R,
were observed, With R,.. remaining constant.

Figure 4 shows the averaged results from
sixteen kidney experiments in which the lowest
RVP required to produce a significant decrease
in renal blood flow, is plotted against control
(zero time) IRVP and TP values, These data
offer evidence that renal blood flow will remain
unaltered in the face of an increased renal vein

pressure until the latter approximates or ex-
ceeds the pre-existing intrarenal pressure (IRVP
and TP). Points at the lower left portion of
the figure were obtained from experiments in
which renal artery pressure was approximately
100 mm. Hg, while those in the upper right
were obtained with renal artery pressures in
the range of 190 mm. Hg. This latter relation-
ship is more in evidence in Fig. 5, in which the
renal vein pressure at which renal blood flow
significantly falls, is plotted against the pre-
vailing renal artery pressure. Figures 4 and 5
combine to show that there is a good correla-
tion between the prevailing renal artery, in-
trarenal venous and tissue pressures, and the
required renal vein pressure necessary to elicit
a significant fall in renal blood flow.

Following the conclusion of experiments on
the isolated perfused kidney, a series of studies
were carried out on the intact, innervated kid-
ney. Findings from seven innervated kidneys
are shown in Fig. 6. It is seen that as renal
vein pressure is increased progressively from 0
to approximately 70 mmHg, there is a decrease
in total renal vascular resistance, Renal artery
pressures (aortic pressures) were essentially
constant during each experiment and ranged
between 105 and 155 mm Hg, When elevated
venous pressures were restored to control
values, there was a good recovery of control
resistance values.

A group of experiments were then carried out
on: five heart-lung perfused kidneys in order
to evaluate resistance effects of constant flow
and constant, pressure perfusion techniques.
Kidneys were alternately perfused in random
order’at both constant renal artery pressure and
constant renal blood flow. Figure 7 contrasts
the results arid shows that at constant flow, an
elevation in RVP produces an increase‘in resis-
tance in most instances, although results were
variable. In experiments in which resistance
rose at constant flow, up to eight minutes was
required at each venous pressure level until
renal artery pressures stabilized. It was also
noted that changes in tissue pressure and kid-
ney weight were greater in the constant flow
perfused kidney following alteration of renal
vein pressure,

-3-


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80
70
60
50
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100 N10 120 130 140 150 160 170 160 190 200
7 RENAL ARTERY PRESSURE (mm Hg)

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Frcurs 5. Relationship of renal artery perfusion pressure and elevated renal vein pressure

values at which

blood flow significantly falls.
(Sixteen heart-lung perfused kidneys)

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Frevas 2. Effect of increased renal vein pressure on renal hemodynamics in the isolated --—~.

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Diagonal line, middle frame, is line of unity between RVP and IRVP, TP.

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Frevny 1. Effert of increased renal vein pressure on renal hemodynamics in the isolated
perfused dog
(renal artery pressure maintained at 160 mm. Hg)
Diagonal wf maida rame, is line of unity between RVP and IRVP, TP.

~4-


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Frevns 4. Relationship of elevated renal vein pressure values, at which a significant de~
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intrarenal venous (IVP).

(Sixteen heart lung perfused Ki2vey3)
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CHR

EFFECT OF INCREASED
VENOUS PRESSURE

ON

RENAL HEMODYNAMICS

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LEXRINGHOUSS
AL SCIENTIFICAND

‘

FEDERAL AVIATION agencr
AVIATION MEDICAL SER’

AEROMEDICAL
CIVIL. AEROMEDICAL RESEARCH
OKLAHOMA CITY, OKLAHOMA

RESEARCH DIVIstON
(CH INSTITUTE

OCTOBER 1962


(Ry)

TOTAL RENAL VASCULAR RESISTANCE
ma Hgscc/min

CONSTANT PRESSURE CONSTANT FLOW
PERFUSION PERFUSION
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2
3
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1.0.
84
+
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t
RENAL VEIN PRESSURE (mm Ng)
}

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Frcuns 7. Effects of increased renal vein pressure on total renal vascular resistance in the
constant flow or constant pressure perfused M
Results contrasted in same kidney during (a) perfusion at constant aterial inflow (Sigma-
motor pump) and (b) perfusion at pierre pressure (Starling shunt device)
five kidneys!

~10—


TOTAL REWAL VASCULAR RESISTANCE (Ry)

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‘ RENAL VEIN PRESSURE (am He)
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Ficuns 6, Intact innervated dog kidneys. Effect of increases in renal vein pressure on
total renal vascular resistance (R,). (7 kidneys)
(kidneys perfused by intact renal artery)
(Mean diterial pressure, 126 mm. Hg}
(Mean control renal blood flow = 3.2 ce./min./gm.)

-~9-


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Frcurs 3, Effect of increases in renal vein pressure on the kidney. Mean values, 16 isolated
i ys.

RENAL WEIN PRESSORE (em/Hg)

(renal artery pressure maintained constant in each experiment)

-6-


METHODS

This investigation was divided between
studies on intact innervated and isolated per-
fused dog kidneys. Sixteen experiments were
carried out on the isolated heart-1 Jung perfused
kidney. The experimental preparation has been
previously described (11-13).

The heart-lung kidney preparation was uti-
lized in all isolated perfused kidney experi-
ments. Adult dogs were administered sodium
pentobarbital, the left kidney was removed
without ‘interruption of renal blood flow and
perfused with heparinized homologous blood
at a controlled renal artery pressure. The ori-
fice renal vein was cannulated with a 3-5 cm.
length of polyethylene tubing fitted with a
rubber sleeve for needle insertion, An adjust-
able screw clamp was placed distal to the rub-
ber section and was used to alter renal vein
pressure. Intrarenal venous pressures were ob-
tained by advancing a small polyethylene
catheter (O.D., 0,7 mm.) through the renal
vein deep into the kidney substance (9, 10).
Tissue pressures were obtained by inserting a
No, 23 needle into the kidney parenchyma and
connecting the needle to a Statham pressure

"-transducer by means of a saline filled catheter
(13). Renal blood flow and urine flow were
measured with a graduated cylinder and stop-
watch, /

The magnitudes and direstional changes of
tissue pressure and deep infra- -renal venous
pressure were similar, as has been reported pre-
viously (9). All pressures were obtained from
catheters attached to pressuye transducery’ and
registered on a Sanborn direct writing regorder.
Orifice renal vein pressure was increased in
stepwise fashion through a wide range (0-100
mm. Hg). Venows pressure was maintained at
eath pressure level from 4 to 6 minutes until
pressures and flows became stabilized. Changes
in the following parameters were observed as
a function of elevated renal venous pressure
(RVP): intrarenal venous pressure (IRVP)
tissue pressure (TP), renal segmental vascular
resistances: R,.. (prevenous or intrarenal re-
sistance), R, (venous segment resistance), Re
(total renal resistance), renal blood flow and

urine flow. Control blood flows in isolated
kidneys averaged 2.8 cc./min./gm, (range, 1.5-
49).

Experiments were also carried out on seven
intact innervated kidneys and five isolated kid-
neys. In the latter instance, results from con-
stant flow and constant pressure perfusions
were compared. Procedures used in the intact
innervated kidney experiments have been pre-
viously described (11). Renal vein blood flow
was measured with cylinder and stopwatch.
The renal pedicle was untouched and renal

- vein outflow was diverted from its usual path

into an extracerporeal circuit and returned to
the jugular vein. Since all contaminating veins
were ligated, venous outflow between pedicle
and site of cannulation (inferior vena cava)
was derived only from the kidney. Renal
venous pressure was increased by a screw clamp
placed on the venous outflow tubing and pres-
sures were measured at the site of the orifice
renal vein. Venous pressures were maintained
at each level until successive blood flows were
in close agreement (3 — 8 min.). Mean aortic
pressures averaged 126 mm Hg. and mean con-
trol renal blood flows were 3.2 cc./min./gm.

RESULTS

Figures 1 and 2 illustrate findings from two
isolated perfused kidney experiments which are
representative of results obtained at different
renal artery, intrarenal venous and tissue pres-
sures, Renal vein pressure is increased in step-
wise fashion in each experiment. In Figure 1,
renal artery pressure was maintained at 160
mm. Hg and gepal vein pressure was increased
from 0.to 97 mm. Hg. Renal blood flow is seen
to remain relatively constant until rena] vein
pressure (RVP) exceeds 75 mm. Hg, a value

, approximately equal to control (zero time) in-

trarenal venbus pressure (IRVP) an tissue
pressure (TP).

Above this pressure, renal blood flow shows
a marked fall from 124 to 99 cc./min., and
RVP, IRVP and TP then rise together in an
approximate 1:1 ratio. Urine flow, on the
other hand, is observed to falt at a venous pres-
sure of 43 mm. Hg. Total renal resistance (R:)
and venous segment resistance (R:) markedly


EFFECT OF INCREASED VENOUS
PRESSURE ON RENAL HEMODYNAMICS

Lemer B, Hinshaw

Charles M. Brake
P. F. lampietro
Thomas E, Emerson, Jr.

ABSTRACT

Conflicting evidence exists in regan to the effects of increased venous pressure on renal

hemodynamics.” E
nervated or isolat

riments. to clanfy its role were carried out on twent-cight intact in-
perfused dog kidneys. Findings indicate the absence of a “venous-

arteriolar” refler. Decreases in total resistance occur as venous pressure is increased through

a wide range in both innervated and isolated
and blood flow are unaffected by

perfused Kidneys. Intrarenal venous and tissue
rf

ge increases in venous pressure, (21-75 mm.

Fig), although venous segment resistance techies markedly. Decreases in blood flow are

seen when

renal vein pressure approaches or exceeds intrarenal venous and tissue pressures,

Results confirm previous investigations regarding the importance of tissue pressure and in.

trarenal venous pressure in renal

lynamics, which appear to “buffer” the kidney against

effects of elevated venous pressure through a variable but unusually large venous pressure

range. The phenomenon o!
blood flow constancy in the face

INTRODUCTION ‘

The effect.of increased real venous’ pressure
on renal hemodynantics is poorly understood
and there is considerable conflict in the results
obtained by various investigators (1-6). At-
tempts have been’ made to’ assay the role of
venous pressure in certain ‘clinical conditions,
but jits effect on renal pressure-flow sélation-
ships is debatable (7). Haddy and others (3,
6) reported an increase in renal resistance in
the innervated Kidney and a decrease in the
denervated kidney as a function of renal vein
pressure elevagion. On the other hand,
Ochwadt (4) and Waugh and Hamilton (3)
observed an increase in renal resistance in the
isolated perfused kidney ds a result of elevation
of renal vein pressure, Ochwadt considered
his findings to bear on the mechanism of renal
autoregulation as was also suggested by Semple
and de Wardener (8), Waugh and Hamilton

autoregulation may be extended to include a tendency for renal
wide swings in both renal artery and venous pressures.

pointed out that elevated renal vein pressure
increased total renal vascular resistance by in-
creasing intgrstitial pressure (5).

These previous investigations did not take
into consideration the recent observations
(9, 10), that through the renal artery pressure
range from 70-to 200 mm. Hg, there are large
differences between orifice renal venous pres-
sure and deep intrarenal venous pressure. The
original aim ¢f the present investigation was to
elucidate the mechanism of increased renal re-
sistance following elevation of renal vein pres-
sure, with particular reference to the roles of
deep intrarenal venous and_ tissue pressures.
Results, however, do not confirm the studies of
previous investigators (3-6), but show a de-
crease in total renal vascular resistance as a
function of increased venous pressure in both
intact innervated and isolated perfused kidneys.
The implication of these findings is discussed.

-1-


EFFECT OF INCREASED VENOUS
PRESSURE ON RENAL HEMODYNAMICS

LERNER B. HINSHAW
CHARLES M. BRAKE
P. F. IAMPIETRO
THOMAS E. EMERSON, JR.

with the assistance of

Fred D, Masucci

Rosalie A. LaVon
Environmental Physiology Branch

FEDERAL AVIATION AGENCY
AVIATION MEDICAL SERVICE
AEROMEDICAL RESEARCH DIVISION
CIVIL AEROMEDICAL RESEARCH INSTITUTE
OKLAHOMA CITY, OKLAHOMA
OCTOBER 1962


‘The findings from these studies assign prom-
jnént roles to intrarenal venous and tissue pres-
mikes: they appear to “buffer” the kidney
figainst the effects of elevated renal venous
pressure throughout a variable but unusually
Jarge venous pressure range. A decrease in
total renal vascular resistance occurs in both
solated perfused and intact innervated kidneys
en renal venous ‘pressure is increased
gh a wide range. It is of interest that
decrease in resistance is primarily due to
E the ‘drop in venous segment resistance (R;)
while intrarenal resistance (R.-:) remains rel-
vely constant through a wide range of venous

vein pressure is to distend the vascular seg>
ment from the deep intrarenal veins to the
renal orifice vein. The “pressure buffering”
éffect of intrarenal venous and tissue pressures
ould appear to preserve both normal renal
‘hemodynamics and function in the face of large
F imereases in renal venous pressure, since in-
‘rarenal resistance remains relatively constant.
F Its of interest that this buffering effect is more
f. prominent at the higher renal artery pressure
» range.
| "These findings provide evidence for the ab-
Fgence of a “veni-vasomotor” or “venous-
arteriolar” reflex (3,6) and provide an éxplana-
tion for the discrepancy of the presently re-
F ported results with those of others (3-6). This
|. study shows that during constant flow perfusion
“am increase in renal vein pressure may result
; dm an increase in total renal vascular resistance
F in the perfused kidney, and this has ‘shown
‘by others (4,5). Since the intact kidney is not
’aormally perfused at constant flow, this rise in
resistance is apparently due to the peculiarly
conditions of this technique: blood
driven through the kidney at a constant
low rate in the face of a progressively elevated
al venous pressure, results in a swollen kid-
y, extravascular pressure increases and in-
Jar pressure rises while transmural pres-
‘gemain relatively constant. Two opposing
"appear to operate during constant flow
n when renal vein pressure is increased:

‘The effect of an increase in renal

(a) passive dilation of the venous bed and (b)
compression of blood vessels by increased tis-
sue pressure. The net effect on resistance
changes depends on which force predominates.
During constant pressure perfusion on the other
hand, one force primarily appears to be in evi-
dence, i.e., venous distention, and the result is
a consistent decrease in desistance. Ochwadt's
resistance increases in the constant flow per-
fused kidney were very great (4). He found
that increasing venous pressure to 40 mm. Hg
produced an increase in resistance of approxi-
mately twice the control value. The kidneys,
however, in his experiments were placed within
a hermetically sealed saline filled chamber
which undoubtedly resulted in exaggerated
compression effects with elevated renal vein
pressure at constant flow perfusion.

Urine flow changes were variable, but gen-
erally after a period of relative constancy, de-
clined markedly. This observation is consist-
ent with that of Winton (14) who pointed out
that back-pressure effects of renal vein pressure
on increasing tubular pressure may offset an
increased glomerular pressure. Two opposing —
forces are involved in this instance and the net
effect is variable, particularly with venous pres-
sures in the lower range (0-25 mm. Hg).

The phenomenon of renal autoregulation (i.
e., the tendency for renal blood flow to change
less than expected through a wide arterial pres-
sure range). may be extended on the basis of
the present study, to include a similar phenom-
enon operating at the venous end of the renal
circulation: there is a fairly constant renal
blood flow thiough a wide range of renal
venous pressures. The findings of the present
study provide corroborative support for the
tissue pressure theory of renal autoregulation
(9, 10, 13),’ and suggest that a pre-venous
myogenic reflex resulting from venous disten-
tion, is not operative in the kidney, From the
results of this and other studies (10, 11), in-
trarenal resistance (R..:) appears to be rel-
atively uninfluenced through large increases in
both renal artery and renal vein presures.

It is of interest to consider the physiological
implications of these findings as they relate to

-ll—-