Download The Haemodynamic Effects of Metabolic Acidosis

Clinical Science and Molecular Medicine (1976) 50, 177-184.
The haemodynamic effects of metabolic acidosis in the rat
J . YUDKIN, R. D. COHEN
AND
BARBARA SLACK
The Metabolic and Endocrine and Medical Units,
The London HospitaI Medical College, University of London
(Received 21 August 1975)
Summarv
1. The effect of metabolic acidosis of 4-6 h
duration on cardiac output, blood pressure, heart
rate, and hepatic and renal blood flow has been
studied in the rat.
2. In anaesthetized rats, blood pressure and heart
rate fell linearly with blood pH in both shamoperated and nephrectomized rats. There was no
significant difference between the two groups in the
effect of acidosis on either variable.
3. Cardiac output showed a significant fall with
increasing acidosis in the conscious rat.
4. Estimated hepatic blood flow in wnscious
rats showed a significant positive correlation with
blood pH in both sham-operatedand nephrectomized
animals. There was no significant difference in
estimated hepatic blood flow between the two
groups of animals at any blood pH.
5. In conscious rats, increasing acidosis caused
a progressive decrease in estimated renal blood
flow.
6. It is concluded that the increase in the previously described apparent renal contribution to
lactate removal in the acidotic rat cannot be explained by any circulatory effect mediated by the
kidney. The possible relevance of the findings to
lactate homeostasis is discussed.
Key words: acidosis, blood pressure, cardiac
Correspondence: Professor R. D. Cohen, Unit of Metabolism and Endocrinology, The London Hospital, Whitechapel, London El 1BB.
C
output, hepatic blood flow, lactate metabolism,
renal blood flow.
Introdwtion
In a previous study (Yudkin & Cohen, 1975) it was
shown that in the consciousrat at normal blood pH,
nephrectomy resulted in approximately30% slowing
of absolute lactate removal after administration of
an intravenous lactic acid load. Furthermore, in
severely acidotic rats, nephrectomy produced more
marked slowing of absolute lactate removal than
occurred in rats of normal acid-base status. In the
same study it was demonstrated that renal excretion
of lactate ions could account for only a small
fraction of the renal component of lactate removal.
The slowing of lactate removal with nephrectomy
could theoretically be due to two other mechanisms.
First, the kidney might contribute directly to the
metabolic removal of lactate ions. Secondly,
nephrectomy might iduence lactate removal in the
remainder of the body, either through circulatory
changes, or by some humoral mechanism.
In the present experiments the haemodynamic
effects of acidosis and nephrectomy in the rat have
been studied in order to determine whether the
changes in lactate metabolism seen in the acidotic
animal could result from circulatory changes. The
studies also had the more general purpose of
establishing the detailed pattern of haemodynamic
response to acidosis and included measurement of
hepatic and rend blood flow as well as of heart
rate, blood pressure and cardiac output.
177
178
J. Yudkin, R. D. Cohen and Barbara Slack
Methods
Experimental design
Experiments were performed on male SpragueDawley rats weighing between 200 and 350 g.
There were no significant differences in mean weight
in the various groups of animals studied. The animals
were maintained on a standard laboratory diet
(Dixon's Rat Cake type 41B; E. Dixon and Sons,
Ware, Herts.) and were permitted free access to
food and water. All animals studied in the conscious
state had previously been accustomed to restraining
cages. Measurements were performed on rats of
normal acid-base status, and on rats made acidotic
to various degrees by oral administration of ammonium chloride solution (1.87 mol/l) 4-6 h earlier,
in doses of 15-40 mmollkg body weight.
Blood pressure and heart rate measurements
Measurementswere made on both nephrectomized
and sham-operated rats; these renal operations
were performed by methods previously described
(Yudkin & Cohen, 1975) 4-6 h before the measurements were taken. Blood pressure was recorded
directly from a carotidcannula, inserted immediately
beforehand under light ether anaesthesia,with a semiconductor strain-gauge transducer (type S.E.3/81;
S.E. Laboratories Ltd) and ultraviolet recorder
(type S.E. 2005). Heart rate was measured from
the blood pressure trace. Blood pH was measured
on a sample withdrawn from a right atrial cannula
implanted 1-3 days previously.
Cardiac output measurements
The changes in cardiac output during induction
of metabolic acidosis with ammonium chloride
were determined in three rats; two of these animals
were also studied after administration of similar
amounts of sodium chloride. An electromagnetic
flowmeter (Browning, Pelling & Ledingham, 1969)
was implanted on the ascending aorta 2 weeks before
the experiment, and an aortic polypropylenecannula
(Browning, Ledingham & Pelling, 1970) was inserted
1 week later. Measurements were made on conscious
animals before, and at hourly intervals after,
administration of sodium chloride solution (1 -87
mol/l) or ammonium chloride solution (1.87 mol/l)
in a dose of 40 mmol/kg body weight. An interval of
8 days separated the studies on rats which were
given both solutions. Aortic blood pH was measured
at each time, the volumes being replaced with rat
donor blood. Heart rate was measured from the
cardiac output trace.
Hepatic and renal bloodflow
The small blood volume of the rat imposes
limitations on the volume of blood samples obtained
from these animals; even minor degrees of hypovolaemia substantially reduce hepatic and renal
blood flow (Sapirstein, Sapirstein & Bredemeyer,
1960). An experimental protocol was therefore
devised which required only two blood samples to
be taken. The techniques used depended on analysis
of the rate of decline of blood concentration of
intravenouslyadministeredIndocyanine Green (ICG)
and sodium p-aminohippurate (PAH). In man, the
decay curve of ICG") after an intravenous injection
is of single exponential form (Caesar, Shaldon,
Chiandussi, Guevara & Sherlock, 1961); it has been
assumed that this form of decay curve also occurs
in the rat. The fractional removal rate (KIco)and
volume of distribution (VIco) were determined from
the slope and the zero intercept respectively of the
line joining two values of ICG concentration obtained at two time-intervals after injection and
plotted on semilogarithmicpaper. Hepatic extraction
of the dye (EICG)at various blood pH values was
measured in a separate group of animals and these
values were used to obtain an estimate of hepatic
blood flow (ml min-I kg-I body wt.) as follows:
Hepatic blood flow
(min-I)
- VICG (ml/kg body wt.) x Klcc
Eicc x (1 - PCV)
where PCV represents packed cell volume, assumed
to be 0.42 (Yudkin & Cohen, 1975).
The decay curve of PAH after an intravenous
injection in dogs is of double-exponential form
(Mandel, Vidt & Sapirstein, 1955), and evidence
was presented by these workers suggesting that the
more rapid exponential represents distribution of the
substance, and the slower exponential represents
excretion. It has been assumed that a similar decay
curve occurs in the rat, and that in the nephrectomized animal the decay curve is of single exponential
form to a plateau concentration which represents
equilibration of the substance in the total volume of
distribution. It has further been assumed that at any
(') Abbreviations:
ICG,
p-aminohippurate.
Indocyanine Green; PAH,
Haemdynamic effectsof acihsis
value of blood pH the volumes of distribution of
PAH and the distribution constant are unaffected
by nephrectomy. Given these assumptions, the
principle of the method is to obtain the characteristics
of the fist exponential (i.e. distribution) from
observations in the nephrectomized animal at
different blood pH values and to use this information
to extract from the data obtained in the shamoperated animals the characteristics of the second
exponential (i.e. excretion).
Values were obtained for plasma concentration of
PAH after complete distribution ( Pm ) by withdrawing a single blood sample from the nephrectomized rat 30 rnin after an intravenous injection of
PAH. The total volume of distribution of PAH
(VmPAH)
may be calculated from these values. In
another group of nephrectomized animals, blood
samples were withdrawn at 4 and 8 rnin after
administration of PAH. From the measurements of
PAH concentrations at these times, and the extrapolated value at t = ffi (Pm), it is possible to
calculate (Yudkin, 1975) the following three values
by the method shown in the table deposited with the
Librarian, The Royal Society of Medicine, 1
Wimpole Street, London W1M 8AE (Clinical
Science and Molecular Medicine, Table 7518;
copies may be obtained by application to the
Librarian): the theoretical plasma concentration of
PAH at zero time (Po),the theoretical initial volume
of distribution (VopAH),and the distributional
constant (KZpAH).For sham-operated rats, blood
concentrations of PAH were determined at 4 and 8
min after intravenous administration of PAH, and
by using these figures supplementedwith appropriate
vdues ofPo,P mand KIPAH
obtained from regression
lines of these variables against blood pH obtained
from observations on nephrectomized animals, the
excretoryfraction removal rate (KZpAH)
was calculated. Renal blood flow was derived as in the deposited
Table (see above) from the values of yopAH
and
KZpAH,
and from estimates of renal extraction of
PAH ( E p A H ) at various blood pH values made in a
separate group of animals:
VOPAH
x KjPAH
Renal blood flow =
EPAH
x (1 - PCV)
where PCV is the packed cell volume, assumed to be
0.42 in all experiments.
The experimental design consisted of administration of a bolus of ICG and PAH to the conscious
resting rat through a right atrial cannula 4-6 h
179
after either nephrectomy or sham-operation, and
after administration of ammonium chloride solution
as described previously. The doses given were ICG
5.16 mollkg body wt. and PAH 51-5 mollkg
body wt. in a volume of 2.5 mllkg body wt. Blood
pH was measured on a preinfusion sample. At 4
min and 8 min after the injection, a sample of blood
(0.5 ml) was withdrawn from the cannula in the
opposite jugular vein for determination of ICG and
PAH concentrations. In a separate group of bilaterally nephrectomized rats, a single sample was
withdrawn 30 rnin after injection for determination
of PAH concentration.
Af'ter completing the observations on each shamoperated rat, the animal was anaesthetized with
sodium pentobarbitone (0.24 molll), 1 mlFg body
wt. by intraperitoneal injection. A constant infusion
of a mixture of ICG and PAH was commenced
through a right atrial cannula to administer approximately ICG, 0,323 m o l min-' k g - I body
wt. and PAH, 3.09 rmol min-1 kg-I body wt. A
tracheostomy was performed and the animal
ventilated. Approximately 10 min after commencing
the constant infusion, an abdominal and thoracic
incision was made and blood samples (0.5 ml) were
withdrawn in turn from the right renal vein and the
abdominal aorta. Clamps were then placed on the
inferior vena cava just caudal to the liver, and on the
inferior vena cava at its junction with the right
atrium, and a further blood sample (0.5 ml) was
withdrawn from the inferior vena cava between the
clamps. The whole procedure took less than 1
min in each experiment. Aortic blood was analysed
for pH, and for ICG and PAH concentration; renal
vein and inferior vena cava ('hepatic vein') blood
were analysed for PAH and ICG concentrations
respectively. The percentage extractions of ICG
and PAH (EIco and EPAH)
were then calculated.
Analytical methods
Blood pH was measured with a blood microsystem acid-base analyser (model BMS-3; Radiometer, Copenhagen) standardized with buffers of
nominal pH 6.841 and 7.383.
ICG was determined in diluted plasma within 3
h of taking the blood sample by measurement of
extinction at 805 MI. Readings were unaffected by
alteration of pH between 5.5 and 7.5, and by the
presence of PAH in the plasma in concentrations
above those reached in the current experiments.
J. Yudkin, R. D. Cohen and Barbara Slack
180
The determination of PAH was made on plasma
samples diluted 1:2 in sodium chloride solution
(154 mmol/l) by the Autoanalyser method of Harvey
& Brothers (1962). Alteration of pH between 6.6
and 7.4 had no effect on the readings of PAH
obtained, and the presence of ICG in plasma in
concentrations covering the range found in the
current experiments was also without effect on the
readings of concentration of PAH.
Statistical methods
Statistical analysis of the data was performed by
non-paired Student's t-tests, or by the non-parametric Mann-Whitney U test (Siegel, 1956) for
non-normally distributed data or when groups were
compared in which variances were unequal as
judged by Fisher's F-test. Simple linear regression
analysis was also used (Snedecor & Cochran, 1967).
Comparison of two regression lines was performed
by computer with the methods described in Geigy
Scientific Tables, 7th edn, pp. 178-179. Mean values
are expressed f 1 SEM.
Results
Effect of acidosis and nephrectomy on blood pressure
and heart rate
Both blood pressure and heart rate fell linearly and
highly significantly with pH (Fig.1). The regression
122
r( a )
0
/
0
lines for sham-operated and nephrectomized rats
were not significantly different (blood pressure
P > 0.05, heart rate P >0.4).
Efect of acidosis on cardiac output
The electromagnetic flowmeter technique used in
these studies is not able to provide absolute values
for cardiac output, but can measure changes in
cardiac output in the same animal (Browning et al.,
1969). In two rats to which sodium chloride solution
was given, there was no significant trend in cardiac
output over 6 h; the mean value varied between
77.3% and 103.3% of control values. In three
conscious rats made acidotic with ammonium
chloride, the cardiac output showed a significant
fall during the 5 or 6 h of observation. There was a
significant positive regression of cardiac output on
aortic blood pH as shown in Fig. 2(a) (datafrom
all animals). Heart rate in these conscious animals is
shown in Fig. 2(b) and also slows significantly with
acidosis. There was a fall in heart rate of approximately42Z between pH 7-4 and 6.7, whichis similar
to the findings in anaesthetized rats, shown in Fig.
I@).
Efect of acidosisandnephrectomyon hepatic bloodflow
Hepatic extraction of Indocyanine Green (EIcG)
was measured in anaesthetized rats, and fell signific-
@/
4oot
00.0.
0
0
0
9 0 1
67
I
6.8
I
I
I
6.9 7.0 7.1
I
7.2
01
7.3
1
I
7-4 7.5
200
67 6 8
6.9
7.0 7.1
7.2 7.3
7.4 7.5
Preinfusion right alrbl blood pH
FIG. 1. (a) Relation of mean carotid artery pressure to blood pH in sham-operated ( 0 )and nephrectomized ( 0 )
rats. pH was measured on right atrial blood. The linear regression lines are: for sham-operated rats, blood pressure
= -70.2f24.8 (pH)(Pe0.02,
r = 0.61) and, for nephrectomized rats, blood pressure = 133.0f 33.6 (pH) (P
i0.01, r = 074). (b) Relation of heart rate to right atrial blood pH in sham-operated (0)and nephrectomized
(0)rats. The linear regression lines are: for sham-operated rats, rate = -875+168 (pH) (P<OOOl, r = 0.92)
and, for nephrectomized rats, rate = - 1089+198 (pH)(P<OOOI, r = 092).
-
181
Haemodynamic effects of acidosis
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antly with increasing acidosis (P<OO2, n = 19);
the mean values of EICGfrom the regression line
are 69.9% at pH 7-4 and 49.9% at pH 6.7.
The relationship between KIc0 and right atrial
blood pH is shown in Fig. 3(a). It m a y be seen that
in both sham-operated and nephrectomized rats,
KIc0 was unaffected by a reduction in blood pH
until the value for pH falls below 7.1. At greater
degrees of acidosis there was a similar fall in Krc0
in both groups. The values of estimated hepatic
blood flow inconscioussham-operatedandnephrectomized rats at varying blood pH is shown in Fig. 3(b).
There is a significant positive regression of estimated
hepatic blood flow on right atrial blood pH in both
groups of rats, and the gradients of these regression
lines are very similar (sisnificance of difference
between gradients P 0.3). Estimated hepatic blood
flow in rats at normal pH was approximately 55 ml
min-' kg-l body wt. in both groups and this fell to
between 10 and 15 ml min-I kg-1 body wt. at
pH 6.7. There is no plateau apparent for the values
of estimated hepatic blood flow in either group
between blood pH 7.1 and 7-5.
It should be noted that the calculation of estimated
hepatic blood flow assumes a constant packed cell
volume of 0.42 whereas in acidotic animals the
packed cell volume is approximately0.05 higher than
at normal pH (Yudkin & Cohen, 1975). This assumption will produce an underestimate of esti-
=-
-
I
0
I
I
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mated hepatic blood flow of 9% in severe acidosis
for which no correction has been made.
Effect of acidosis on renal bloodfTow
The total volume of distribution of PAH (VmPAH)
in nephrectomized rats did not vary significantly
with pH (P>O*6, n = 12); the values derived from
the regression line are 332 ml/kg body wt. at pH
7.4 and 355 ml/kg body wt. at pH 6-7.
In a separate group of nephrectomized rats, the
theoretical volume of distribution of PAH at zero
time (VopAH)and the distributional constant for
PAH (KIPAH)were determined. The gradients of the
regression lines of VoPAHand KZPAH
on right atrial
blood pH do not differ significantly from zero
(P>O.l, n = 20 for VOPAH
and P > 0 - 4 , n = 20 for
KIPAR).
The mean values for VOPAH
derived from
the regression lines are 164 ml/kg body wt. at pH 7.4
and 138 ml/kg body wt. at pH 6.7. The corresponding
values for KIPAH
are 0.155 min-' at pH 7.4 and
0.130 min-I at pH 6.7.
The renal extraction of PAH (EpAw)
was determined in anaesthetized rats and fell significantly
with increasing acidosis (P<OOZY n = 23); the mean
values of E p A H from the regression line are 83.4%
at pH 7.4 and 68.7% at pH 6.7.
The derivation of excretory fractional removal
rate (KzPAH)for sham-nephrectomized rats was
J. Yudkin, R . D. Cohen and Barbara Slack
182
0 0
8,
70-
- c
W
L
I
I
I
I
I
I
6 6 6? 6 8 6.9 7.0 7.1
I
I
7-2 7.3
1
1
7.4 7 5
1
1
1
1
1
1
65 6 6 6? 66 6.9 7-0 7.1
1
1
1
1
7.2 7.3 7.4 7.5
Right driol blood pH
FIG.3. (a) Relation of fractional removal rate of Indocyanine Green (KIcO)to blood pH in sham-operated (0)
and nephrectomized (0)rats. pH was measured on preinfusion right atrial blood. (b) Relation of estimated hepatic
blood flow to right atrial blood pH in sham-operated (0) and nephrectomized (0)rats. pH was measured on
preinfusion right atrial blood. Estimated hepatic blood flow (EHBF) is expressed per kg body weight. The linear
regression lines are: for sham-operated rats, EHBF = - 3 4 4 6 + 53.9 (pH) (P<0.001,r = 0.83) and, for nephrectomized rats, EHBF = 424.1 64.7 (pH) (P<0,001,r = 0.83).
-
+
made according to the method described above. The
values for estimated renal blood flow in shamnephrectomized rats at various blood pH values
were then calculated from KZPAH
and are shown in
Fig. 4. There is a significant positive regression of
estimated renal blood flow on blood pH. The mean
value for estimated renal blood flow falls from 98
ml min-' kg-' body wt. at pH 7.4 to 50 ml min-'
kg- body wt. at pH 6-7.
I40
1
6-5 6 6 6.7 6% 6.9 7Q 7.1 7.2 7.3 7 4 7.5
Right atrial blood pH
Fro. 4. Relation of estimated renal blood flow to preinfusion
right atrial blood pH in sham-nephrectomized rats. Estimated
renal blood flow (ERBF) is expressed per kg body weight.
The linear regression line is ERBF = -407*9+68-3 @H)
(Pc0.001,r = 0.63).
The calculation of estimated renal blood flow
assumes a constant packed cell volume of 0.42,
and, as noted fof hepatic blood flow, the assumption
produces an underestimate of renal blood flow of 9%
in severe acidosis.
Discussion
In the rat, metabolic acidosis of 4-6 h duration
produced marked effects on cardiac output, heart
rate, blood pressure, and hepatic and renal blood
flow. At a blood pH of 6.7 cardiac output was
reduced by 40% compared to that found at pH
7.4. For the same decrease in pH, heart rate fell by
34% in anaesthetized rats and 42% in conscious
rats; mean arterial blood pressure was reduced by
17%, hepatic blood flow by 76% and renal blood
flow by 49%. The changes in blood pressure, heart
rate and hepatic blood flow with acidosis were
similar in nephrectomized and in sham-operated
rats. The fall in cardiac output in acidosis was
mainly due to a fall in heart rate, with no change
in stroke volume. However, the lack of compensatory rise of stroke volume suggests a negative
inotropic action of acidosis (see also Smith &
Corbascio, 1966; Wildenthal, Mierzwiak, Myers &
Mitchell, 1968) in addition to the chronotropic
effect.
Haemodynamic efects of acidosis
Measurements of blood pressure were performed
on anaesthetizedrats whereasall otherhaemodynamic
studies employed conscious resting animals. In
rats of normal acid-base status, blood pressure
measurements by tail plethysmography under light
ether anaesthesia correlate well with measurements
by an ankle cuff and photoelectric cell in conscious
a n i d s (Floyer, 1951). It should be noted that in
the studies in conscious animals, previous operation
had been required for sham- or actual nephrectomy,
insertion of cannulae and flowmeters; the influence
of such procedures on the results is unknown.
The necessity for restriction of blood sampling
in the measurement of hepatic and renal blood flow
precluded the usual technique of obtaining many
samples at intervals and applying an exponential
curve-fitting analysis. The method employed to
measure hepatic blood flow depends on two assumptions: first, that the decay curve of ICG in the
rat is of single exponential form, and secondly that
hepaticclearanceof ICG is &&ed
by anaesthesia.
There is no evidence in the literature on these points.
The calculation of renal blood flow requires four
assumptions to be made. First, the extraction of
PAH by the kidney should be unaffected by anaesthesia. Secondly, the double-exponential decay
curve of PAH concentration seen in the dog should
also apply in the rat, and the two components of
this curve should represent distribution and excretion of the substance. Thirdly, the volumes of
distribution of PAH and intercompartmental
exchange should be unaffected by nephrectomy.
Finally, the tubular transport mechanism for PAH
should not be saturated at the plasma concentrations
attained. We have no formal evidence to subtantiate
the first three assumptions, but the fourth is substantiated by the &ding of Friedman, Polley &
Friedman (1947) that PAH transport mechanisms
in the rat under normal acid-base conditions were
only saturated at plasma concentrations in excess of
those used in the present study.
Most of the previousstudieson the haemodynamic
effects of acidosis have been performed in the
anaesthetized ventilated dog at constant P a z and
thus differ from the present studies in which respiratory compensation for metabolic acidosis
occurs. In the anaesthetizeddog, cardiac output and
heart rate fell with metabolic acidosisbut the changes
of blood pressure were variable (Smith & Corbascio,
1966; Kittle, Aoki & Brown, 1965).
Hepatic blood flow in the anaesthetized dog
183
ventilated at constant rate did not alter with reduction of blood pH to a mean value of 7.1 (Goldstein, Simmons & Tashkin, 1972). Measurements
were not made at lower pH values. It was noted in
the present experiments that KIcoremained constant with reduction in blood pH to 7-1 but no such
plateau was apparent in estimated values of hepatic
blood flow (Fig. 3a and Fig. 3b). The calculation of
estimated hepatic blood flow from KIcorequires
multiplication by the volume of distribution of
ICG; it is possible that the greater variability in
values of estimated hepatic blood flow introduced by
this calculation might disguise any apparent plateau
in the relation of estimated hepatic blood flow to
blood pH. The estimata of hepatic blood flow at
normal blood pH were similar to those found by
Ossenberg, Denis & Benhamou (1974) in anaesthetized rats (66 ml min-' kg-I body wt.)
In the anaesthetized dog, renal blood flow showed
little change when blood pH was r e d u d to 7.1-7.2
by infusion of hydrochloric acid (Kittle et al., 1965;
Bersentes 8 Simmons, 1967) but with further reduction in blood pH, renal blood flow fell significantly. Estimated values of renal blood flow in rats
of normal acid-base status were slightly higher
than those derived from the figures of Friedman
et al. (1947); estimated renal blood flow may be
calculated as 77 ml min-l kg-' body wt. from their
data.
Studies of lactate handling by the liver and kidney
in the dog have demonstrated important differences
between the two organs. If hepatic blood flow is
reduced by obstruction of hepatic artery and portal
vein, lactate uptake by the liver remains constant
until the reduction of total hepatic blood flow
exceeds 75% (Tashkin, Goldstein & Simmons,
1972). In the dog kidney, however, graded reduction
in blood flow produced proportional reduction in
renal lactate uptake (Levy, 1962). In a previous
study (Yudkin & Cohen, 1975) it has been demonstrated that, in the severely acidotic rat, the absolute
renal contribution to lactate removal increased while
the extrarenal component of lactate removal was
reduced. If it is assumed that hepatic lactate handling
in the rat is similar to that in the dog, then part of
the reduction in extrarenal lactate removal in
severely acidotic animals may have resulted from the
reduction of hepatic blood flow to critical levels.
However, Lloyd, Iles, Simpson, Strunin, Layton &
Cohen (1973) demonstrated reduced uptake of
lactate by the isolated rat liver perfused with medium
184
J. Yudkin, R . D. Cohen and Barbara Slack
below pH 7.1 in spite of constant perfusate flow
rate, demonstrating that acidosis has an effect on
lactate uptake other than that mediated via hepatic
blood flow. There is no evidence from the present
work to suggest that the increase in the apparent
renal contribution to lactate removal in the acidotic
rat is mediated through any general haemodynamic
effect of the kidney. The increase in this renal
contribution in severe acidosis occurs in spite of a
substantial reduction in renal blood flow, suggesting
that lactate extraction by the kidney increases
markedly in the acidotic animal.
These findings may be relevant to the clinical
condition of lactic acidosis. It is possible that in
idiopathic or type B lactic acidosis (Lancet Editorial,
1973) the terminal shock which is sometimes observed may result from the effect of acidosis on
cardiac output. Furthermore, hepatic blood flow
in the acidotic rat was more sensitive to blood pH
than was renal blood flow; if the same applies to
acidosis in man, the kidney may assume an increasingly important role in removal of lactate from
the circulation in acidosis. In lactic acidosis associated with circulatory failure, the ability of the
kidney to remove lactate from the circulation may be
impaired by a reduction in renal blood flow.
Sriussadaporn & Cohn (1968) found net renal
lactate output in four of eight patients with lactic
acidosis due to shock, and net hepatic lactate output
was Seen in two of four patients with this condition.
AcLnowledgments
We are grateful to Mr C. Browning for valuable
assistance during the studies of cardiac output.
We are also most grateful to Mr Michael Rablen,
who derived the equations for the calculation of
renal blood flow, and to Mr Ashley Hyams, who
constructed computer programs to solve the
equations for renal blood flow by the method
described.
References
BERSENTES,
T.J. & SIMMONS,
D.H. (1967) Effects of acute
acidosis on renal haemodynamics. American Journal of
Physiology, 212,633-640.
BROWNING, C.. LEDINOHAM,
J.M. & PELLING, D. (1970)
Simultaneous measurement of cardiac output and mean
arterial pressure changes in unanaesthetized rats. Journal
of Physiology (London), u)8,ll~-12~.
BROWNING,
C., PELLING, D. & LEDINGHAM,
J.M. (1969)An
electromagnetic flowmeter for studying changes of cardiac
output in unanaesthetized rats. Medical and Biological
Engineering, 7, 549-558.
CAESAR,
J., SHALDON,
S., CHIANDUSSI,
L., GUEVARA,
L. &
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