Fractionation of the Cardiac Output of Rats
with Isotopic Potassium
By
LEO A. SAPIKSTEIN, P H . D . ,
M.D.
A single injection of K42 given intravenously is initially distributed among the organs in proportion to the blood flow through them. By determining the organ content of K41 after such an injection the cardiac output may be fractionated. The conditions and limitations of the method
are discussed and values are given for the fractional distribution of the wireline output in the nit.
A
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FOREIGN substance, after a single
intravenous administration, will be
distributed initially to the organs in
proportion to their blood flow. The substance
will then be carried away from the organs by
their venous drainage. For a certain period of
time, however, the venous drainage will be
negligibly small compared to the arterial
delivery. During this time the fractional
distribution of the substance among the organs
will correspond to the fractional distribution of
the cardiac output among them.
In the case of a substance which is incompletely transferred from the blood to the
tissues, or one which has a small volume of
distribution within the tissues, the time during
which the venous drainage is small will be
short. The time will be greatest for substances
which are completely transferred from the
vascular system to the tissues with least
hindrance and which have a large volume of
distribution within the tissue. The radioactive
isotope of potassium, K42, is such a substance.
The studies described here indicate that the
venous drainage of Iv" is negligible compared
with its initial deposition in the organs of the
rat for at least 1 min. after a single intravenous
administration of the isotope. It is therefore
possible to estimate the fractionation of the
cardiac output of the rat by determining the
distribution of IC 2 in the organs of the animal
killed within 1 min. after intravenous injection
of the isotope. This has been done for the kidneys, splanchnic viscera, heart, brain, skin and
carcass of anesthetized rats.
METHODS
Forty fasting adult male nits were anesthetized
with intraperitoneal sodium pentobarbital 44 mg./
Kg. A femoral vein was exposed and 0.50 ml. of high
specific activity K c (about 200 nie./Gm.) containing
5-10 microcuries was injected rapidly. This injection
was followed at times ranging from 5 to 1200 sec. by
the intravenous administration of saturated KOI
which produced cardiac arrest within 2 to 5 sec.
The organs, including the skin, were removed,
drained of blood, weighed, and digested in hot 6X
HC1. The carcass, including all organs not .specifically taken for analysis, was ground in a meat
grinder, and an aliquot taken for acid digestion.
The K u content of each digest was determined on a
1 ml. aliquot using an end window Geiger-Muller
tube. All organ counts were referred to the arithmetic
average of two counts of a standard K42 solution
which bracketed them closely in time.
RESULTS
Table 1 shows the results in 40 consecutive
measurements. The first 17 rats used were from
a different group than the last 23 and had significantly smaller hearts and kidneys in relation to their body weights. There were corresponding but greater differences in the uptake
of K42 by these organs and the data are therefore presented separately. Xo explanation is
available for the large difference in heart and
kidney Iv12 uptakes in the 2 groups.
The scatter of the results from animal to
animal, even within each group, is considerable.
Nevertheless, there is no evidence of a trend
From the Department of Physiology, The Ohio
Stuto University, Columbus, Ohio.
Supported by grants-in-aid from the American
Heart Association and the Central Ohio Heart Association. A portion of this work was performed as part
of a contract botween the USAF School of Aviation
Medicine, Randolph Field, Texas and the Ohio State
University Research Foundation.
Received for publication July 2, 1956.
6S9
Circulation Kesrarck, Volume IV, Nwrmbcr 19S6
690
FRACTIONATION OF CARDIAC OUTPUT
TABLE 1.—Distribution of K*1 in the Organs of Rats
after Single Intravenous Injection as a
Function of Time
Percent injected R a in orgsn*
Rat Tlmr
(•«.)
Port*!
system Liver Kidney Heart Brain Carcass Skin
Group 1
1
2
3
4
5
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0
7
S
9
10
11
12
13
14
5
7
7
10
15
20
20
20
30
40
50
60
60
170
300
600
15
16
17 1200
12.0
13.1
15.6
15.3
15.0
13.9
12.6
14.3
12.7
11.5
14.2
16.0
19.0
15.0
12.8
15.2
11.9
8.3
4.7
5.0
S.5
8.8
4.4
5.3
5.0
3.3
4.6
4.5
5.8
S.2
7.3
4.1
7.3
8.1
15.0
13.9
10.9
21.2
IS.3
16.5
15.5
13.5
13.5
12.2
17.S
12.S
15.8
10.8
7.8
4.S
3.4
1.8
1.6
1.4
1.6
1.9
0.2
0.1
0.1
0.2
0.2
2.2
1.7
1.6
2.3
1.9
0.5
0.2
0.1
0.2
0.1
0.1
0.1
1.4
1.4
1.3
O.S
1.0
1.0
0.9
Group 2
1
2
3
4
5
6
7
S
9
10
11
12
13
7
9
15
15
25
25
25
40
40
60
60
120
120
14
15
16
17
IS
19
20
21
22
180
180
300
320
440
450
600
600
600
23 1200
14.2
15.7
14.9
12.1
11.7
19.6
11.2
12.4
11.2
13.5
14.6
12.6
14.4
13.0
16.0
17.0
19.6
12.7
19.0
13.1
12.0
14.3
15.5
8.6
7.4
7.2
S.5
11.7
5.3
4.1
6.0
4.7
5.3
10.2
6.4
7.8
6.0
11.4
8.0
25.2
20.4
21.9
22.6
29.S
16.9
IS.9
17.4
32.S
26.1
26.7
17.6
20.6
24.7
13.1
2.S
3.1
3.8
2.9
3.4
2.4
2.9
3.2
4.0
4.5
3.2
3.0
2.6
2.5
5.1
15.5 3.6
9.5 16.9 3.4
8.8 13.4 3.8
10.S 10.2 3.1
7.6
6.4
8.5
9.S
10.0
11.3
7.3
4.0
2.2
3.1
3.1
0.3
0.3
0.4
0.3
0.2
0.3
0.2
0.3
0.2
0.3
0.2
0.5
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.2
0.2
O.S
44.4
34.6
31.0
34.4
39.0
37.6
45.0
45.2
35.4
37.0
43.1
46.5
59.5
39.3
45.6
41.0
44.0
45.5
42.S
44.4
29.S
3S.2
3S.4
S.I
5.6
S.O
4.0
7.9
7.4
5.5
5.5
4.5
6.3
5.6
7.6
5.0
6.2
9.1
7.S
6.5
7.6
4.S
S.7
9.6
* 100 x c p. m. in Organ /c.p.m. injected
either upwards or downwards in the K42 uptake of any organ for at least 1 min. Unmistakable evidence of a downward trend appears
first in the kidney after 3 min.
The average values during the first minute
of 18.1 per cent for kidney, 14.3 per cent for
the portal system, 6.6 per cent for the liver,
2.6 per cent for the heart, 6.3 per cent for the
skin and 38.8 per cent for the carcass are therefore believed to describe the fractions of the
cardiac output distributed to each organ. In
the case of the liver, the fraction detected is
only that which has not previously been
through another vascular bed. The total
hepatic blood flow fraction is the sum of the
"liver" and "portal system" fractions.
Of the injected Iv", 93 per cent was accounted for in those experiments in which
skin and carcass determinations were made.
Ninety seven per cent of the mass of these
animals was recovered.
DiscussroN
The present method is based on the principle
that for a short time after any foreign substance enters an organ by way of the arterial
circulation it does not appear in the venous
circulation. During this time the extraction
ratio is 1.00. Consequently, the clearance of
the substance by each organ will be equal for
a short time to its blood flow. Since the clearance may be described as the ratio between
organ uptake and arterial concentration, and
since the arterial concentration is presumably
constant in all organs, the uptakes will be
divided among the organs in proportion to
their flows.
With the passage of time a sufficient quantity
of measuring agent will accumulate in each
organ to force a significant re-entry into the
venous circulation. This will occur most
rapidly in organs with perfusion rates which
are high in relation to their capacity to contain
the agent. Since the re-entry is not a simultaneous event for all organs, the extraction
ratios will become different from 1 and unequal. The deposition of the measuring agent
will now yield false values for flow. In the case
of organs with high perfusion rates the apparent fractional flow will become falsely low;
organs with low perfusion rates will yield fractionalflowswhich are correspondingly high.
Since, in the present experiments, the first
minute failed to reveal a systematic decline in
the apparent perfusion rates of well perfused
691
SAPIRSTEIX
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organs or a systematic increase in the apparent
perfusion rates of poorly perfused organs, it
must be concluded that entering Iv42 is, so to
speak, "trapped" for this time by all the
organs studied. It is possible that the brain
represents an exception to this situation, and
that the decline in brain potassium occurs with
such extraordinary rapidity that it is essentially complete before the 5 sec. period at which
the first observation was made. This would
occur if the cerebral blood flow were exceedingly large in relation to the cerebral "sink"
for potassium. A small reservoir of exchangeable potassium in the brain has been observed
by others.1 The possibility cannot, however, be
excluded that the cerebral blood flow is correctly measured in these experiments and that
it is much lower than is ordinarily believed to
be the case. If the cardiac output of the rat is
taken as 210 ml./Kg./min.* then the values
given here represent a flow of about 0.1 ml./
min./Gm. of brain tissue. Although this value
is much smaller than that reported in other
species (about 0.5 ml./min./Gm.) it may not be
unreasonably small for the deeply anesthetized rat.
The sum of the fractional values indicated
for the hepatic arterial (liver) flow, and the
hepatic portal (portal system) flow is the
hepatic blood flow fraction. The fraction (20.9
per cent of the cardiac output) is somewhat
higher than that ordinarily accepted, although
the distribution between the arterial and
portal flows is consistent with that previously
reported.3 The discrepancy in total flow may
be explained by a species difference; on the
other hand, it is possible that the accepted
values, based upon hepatic venous catheterization are falsely low.4
The cardiac uptakes of Iv12 differed radically
in the 2 experimental groups. In the first
group, the heart received 1.8 per cent of the
isotope; in the second it received 3.3 per cent.
These values correspond to flows of 1.5 and 2.6
ml./min./Gm. of heart. Such values exceed
those found in the dog by the nitrous oxide
method6 considerably. Whether a species difference is involved or whether the nitrous oxide
method is inapplicable to the heart* is not clear.
It may be noted at this time, however, that
the present method cannot yield falsely high
values for an organ with a high perfusion rate,
so that the value found here represents a
minimum coronary flow.
The value for renal blood flow found in the
first group of animals was about 3.5 ml./min./
100 Gm. rat. In the second group of animals,
the value was about 5.9 ml./min./lOO Gm. rat.
Assuming a 50 per cent hematocrit, both
values give renal plasma flows well within the
ranges reported for normal rats.7
The blood flow through the skin, about 6 per
cent of the cardiac output, for an organ making
up some 20 per cent of the body mass, may be
typical only of the deeply anesthetized animal
in a relatively cool (26 C.) environment.
The carcass, consisting primarily of bone and
muscle, received almost 40 per cent of the
cardiac output, and made up 66 per cent of
the mass of the animals.
SuMMAKY
Intravenously injected K*2 is distributed
among the organs of rats in the first minute
after injection in the following manner: kidney,
18.1 per cent; portal system, 14.3 per cent;
liver, 6.6 per cent; heart, 2.6 per cent; brain,
0.3 per cent. These values remain essentially
constant between 5 and 60 sec. after injection,
suggesting that the early distribution of isotopic potassium reflects the distribution of the
cardiac output.
ACKNOWLEDGMENT
The author wishes to acknowledge his gratitude to
Mr. Edward Reininger for his assistance. Mr.
Randolph Andrews gave valuable technical assistance.
SUMMARIO IN I N T E K U N O U A
Injectiones intravenose de IC2 es distribute
inter le organos del ratto durante le prime
minuta post le injection in le sequent* maniera: Ren—18,1 pro cento; systema portal—14,3 pro cento; hepate—6,6 pro cento; corde—•
2,6 pro cento; e cerebro—0,3 pro cento. Jste
valores remane essentialmente stabile ab 5 a 60
secundas post le injection. Ergo il pare quo
le distribution precoce de kalium isotopic rcflecte le distribution del rendimento cardiac.
G92
FRACTIONATIOX OF CARDIAC OUTPUT
REFERENCES
1
R., LEIDKRMAN, P. H.: Brain potassium
exchange in normal adult and immature rats.
Am. J. Physiol. 175: 263, 1943.
1
BULLAKD, R. W.: Maintenance of arterial pressure
and cardiac output in the hypothermic rat. Fed.
Proc. 16:28, 1956.
3
BLALOCK, A., AND MASON, M. F.: Observations on
the blood flow and gaseous metabolism of the
liver of unancsthetizeel dogs. Am. J. Physiol. 117:
328, 1936.
KATZMAN,
* KAI'IRSTKIN, L. A., AND REININGER, E.: Catheter
induced error in hepatic venous sampling.
Circulation Research 4: 493, 1956.
6
ECKENHOFF, J. E., HAFKENSCHIEL, ,1. H., HARMEL,
M. H., GOODALE, W. T., LUBIN, M., BIND, R. J.,
AND KETY, S. S.: Measurement of coronary blood
flow by the nitrous oxide method. Am. J. Physiol.
162: 356, 194S.
6
SAPIRSTEIN, L. A., AND OGDEN, E.: Theoretic
limitations of the nitrous oxide method for the
measurement of regional blood flow. Circulation
Research 4: 245, 1956.
'SMITH, H. W.: The Kidney. New York, Oxford
University Press, 1951, p. 531.
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Fractionation of the Cardiac Output of Rats with Isotopic Potassium
LEO A. SAPIRSTEIN
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Circ Res. 1956;4:689-692
doi: 10.1161/01.RES.4.6.689
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