CLIN. CHEM. 32/10,
1849-1853
(1986)
Relationship between Serum Lactate and Ionized Calcium in Open-Heart
Surgery
John Toffaletti,”2
Robert
We studied
16 patients
heart-lung
bypass,
to
H. Christenson,”3
Steve
Mullins,1 and Randall
undergoing
open-heart
surgery and
examine
the relationship
between
ionized calcium and lactate. Blood was sampled at successive stages of the operation for measurement of ionized and
total calcium, lactate, blood gases, pH, hematocrit,
and other
constituents.
We found that correlations
between
ionized
calcium and lactate were positive and statistically significant
(p <0.05),
both among
and within patients.
The linear
regression
of ionized calcium on lactate remained
highly
significant (p <0.0001) after adjustment for variability among
patients and across operative stages as well as after correction for pH and hemodilution. The significant
regressions
between calcium and lactate, both before and after administration of calcium,
indicate a relationship
for calcium and
lactate in patients undergoing
open-heart
surgery.
Ionized calcium
has frequently
been studied in patients
undergoing
open-heart
surgical
procedures involving
heartlung
bypass
(1-10).
Because
of the variation
in surgical
techniques
used for these procedures,
and influences such as
transfusion
of citrated
blood, hemodilution
by fluids, administration
of calcium
salts,
anesthesia,
acid-base
changes,
body-temperature
changes,
and administration
of heparin
and protamine,
ionized calcium
has been reported to increase (9), decrease
(1,2, 4-6, 8), or change little (2,3, 7, 8,
10). More consistent
data have been reported for blood
lactate concentrations
during open-heart
surgery. Lactate
concentrations
in serum increase
several
fold during heartlung bypass,
and may remain above normal for several days
afterwards
(11, 12), possibly
owing to localized
tissue inchemia, to decreased
liver function
from hypoxia, to hypothermia, or to all three. Reportedly,
both calcium
and lactate
increased
markedly
during exercise, although
no relationship between
them was discussed
(13).
Other
studies
indicate
that infusion
of calcium
can increase myocardial
oxygen consumption
and cardiac stroke
work (14), and may be a cause of localized
tissue
necrosis
(15), all of which may relate to the production
of lactate.
In
addition, lactate
is known to bind calcium
(16), which
may
also affect the concentration
of ionized calcium.
Most previous work has focused
upon relationships
among
ionized
calcium,
parathyrin,
and pH, but the potential
contribution
of lactate to homeostasis
of ionized calcium
was not examined. Therefore,
we studied 16 patients
undergoing
openheart
surgery
requiring
heart-lung
bypass,
to determine
the relation, if any, between ionized calcium
and lactate.
Materials
and Methods
Patients.
We
obtained
serial blood
specimens
from
16
of Pathology and2 Clinical Chemistry Laboratory,
Center, Durham, NC 27710.
3Department
of Laboratory Service, Durham V.A. Medical Center, 508 Fulton
Street, Durham, NC 27705.
Received April 17, 1986; accepted July 1, 1986.
‘Department
Duke
University Medical
E.
Harri&
male patients
undergoing
various
“open-heart”
surgical
procedures
requiring
heart-lung
bypass. Twelve
of the 16
patients
were undergoing
coronary
artery
bypass
graft
procedures.
Of the remaining
four patients,
three underwent
surgery
for heart-valve
replacement:
one for the mitral
valve,
one for the aortic
valve,
and one for replacement
of
both. The remaining
patient
we
studied underwent
openheart
surgery
for repair of an atrial
septal
defect.
Open-heart
procedure.
After the patient
has stabilized
under anesthesia
in the operating
room, heparin is administered intravenously
to induce sufficient
anticoagulation
as
determined
by activated
clotting
time. After the surgical
incision, the arterial
and venous systems
are cannulated
and tubing
from the heart-lung
pump is connected
to the
arterial
and venous
catheters, forming
a closed
system
for
maintaining
circulatory and gas exchange
functions
during
cardioplegia.
For the cases included in this study, the bypass
pump
was primed
with a balanced
electrolyte
solution
containing
albumin,
potassium,
heparin, and mannitol.
After activation of the heart-lung
pump, a gradual mixing
period facilitates
accommodation
of the patient’s
system to
hemodilution
concurrent
with transition
to extracorporeal
circulation.
To diminish metabolic
demand in all body organs during
open-heart
surgery,
the patient’s
body temperature
is decreased so as to be within
the range of 20-30 #{176}C.
Before
actual surgical
manipulation
of the heart, cardioplegia
is
induced by cross-clamping
the aorta and infusing a cooled
solution
containing
dextrose
and 20-30 mmol of potassium
chloride
per liter. For the patients
included
here, the cardioplegic state was maintained
for 30 to 90 miii.
Upon completion
of surgery,
the aortic
cross clamp
is
removed and the cardioplegic
fluid is purged,
thereby restoring mechanical
activity
of the heart. Subsequently,
as vital
functions
are carefully
monitored,
the patients
can be
weaned from extracorporeal
circulation by gradual
occlusion of tubing to the heart-lung
pump.
After decannulation,
protamine
sulfate is administered
to inactivate
the anticoagulation
effects of heparin. Calcium
chloride is also administered at this time
to offset the hypotensive
effects of
protamine.
To counterbalance
the patient’s
hemodiluted
state, transfusion
of blood products consisting
of packed
erythrocytes
and fresh frozen
plasma
may
also be given.
Each unit of packed cells had 1 g of calcium
added,
as
calcium
chloride.
Heart-lung
bypass
staging.
To normalize the cases included in this study, we staged each heart-lung
bypass procedure, using criteria
similar to those described by Chambers
et al. (3), viz Stage 1 is the preoperative
period shortly
after
each patient was anesthetized;
Stage 2 is just prior to bypass
surgery after administration
of heparin
for anticoagu]ation,
Stage 3 is during heart-lung
bypass; Stage 4 is at the end of
heart-lung
bypass; and Stage 5 is the postoperative
period
subsequent
to intravenous
administration
of protamine,
calcium,
and transfusion
of blood products.
CLINICAL CHEMISTRY,
Vol. 32, No. 10, 1986
1849
Sampling.
During
each stage of each open-heart procedure, 10 mL of each patient’s
heparinized
blood was obtained by syringe,
capped, and immediately
delivered on ice
to the laboratory.
From this sample, aliquots were promptly
analyzed for lactate and blood gases. The remaining
sample,
approximately
5 mL, was used in analysis for total calcium,
ionized calcium, and albumin.
A few patients could not be
sampled at all operative
stages, particularly
at Stage 4 near
the end of bypass, owing to technical
complications.
Blood-gas
determination.
For determination of pH, Pco2,
and Po we used the 168 p11/Blood Gas System (Corning
Medical,
Medfleld,
MA 02052), following the manufacturer’s
instructions.
All pH, Pco2 and P02 determinations
were
corrected for effects of patient temperature
and hemoglobin
by the method
described
by Kelman
and Nunn (17).
Ionized-calcium
instrumentation.
We used the Nova
8
system
(Nova Biomedical,
Waltham,
MA 02254), following
the manufacturer’s
instructions,
to measure ionized calcium
at 37#{176}C
in blood specimens included
in this study.
Lactate
analysis.
We measured
lactate concentration
in
serum with the Du Pont aca system (Du Pont, Wilmington,
DE 19898). Methodology
for this system is based on monitoring,
at 340 nm and 383 mm, the reduction
of NAD
during conversion of lactate to pyruvate
catalyzed
by lactate
dehydrogenase
(EC 1.1.1.27).
Total
calcium
and albumin
measurements.
We determined concentrations
of total calcium and albumin in all
serum specimens by dry-slide
technology
with the Ektachem
(Eastman
Kodak
Co., Rochester,
NY 14650).
The
Ektachem
system used Arsenazo
ifi, at pH 5.6, and bromcresol green to form dye complexes with calcium and albumiii, measurable
by reflectance
spectrometry
at 680 nm and
630 mm, respectively.
Statistical
methods.
Regression
and correlation
techniques were utilized
to assess the relationships
among
ionized calcium, lactate,
and other measured
variables.
Data
plots over successive
stages
of the operation
were
empirically
examined for each patient, and the linear correlation between ionized calcium and lactate was also estimated and tested for statistical
significance.
Within-patient
correlations
were combined into a single estimate and tested
for heterogeneity
by the method
of Fisher (18). Data stratified by the stage of operation
were used to estimate univariate statistics
as well as bivariate
correlations
among patients in order to delineate
average patterns
and pertinent
changes in variable
relationships
during the course of the
operation.
Finally,
an analysis
of covariance
of all ionized calcium
data was performed
in a two-way
classification
model with
patients
and operative
stages as classification
factors and
hematocrit,
pH, and lactate as the covariables
(18). The
covariable
lactate
was fitted last in the model, in order to
estimate and test the significance
of the linear regression of
ionized calcium
on lactate
after adjustment
for possible
average
effects of patients
and operative
stages as well as
correction,
by linear regression,
for effects of pH and hemodilution
(as gauged by the hematocrit).
This analysis was
also utilized
to partition
the variability
due to linear regression of ionized calcium
on lactate among patients and test
the heterogeneity
of regression
among patients.
Results
Figure 1 shows plots of each patient’s ionized calcium
and
lactate concentrations
across stages of the operation.
Empirical
inspection of Figure
1 reveals
a general
positive
1850
CLINICAL CHEMISTRY,
Vol. 32, No. 10, 1986
54
15
4
1.0
2
0.5
0
l02FS/
1.5 4
050
1.0 2
0.5
?
I
--.
-#-‘
0
1.5 4
i5:r,o
1.5 4
1.0
1.0
0.50
2
050
050
.
2
_r_51,
.5
.
4
1.5 4
1.5
4
1.0 2
10 2
1.0
21%o
,
0.50
050
r.
.
,
050
5
4
-J
S...
0
2.5
1.02[./
2.0
0.50
1.5
15
4
1.0
10
2
05
05
0
1.5 4
1.5 4
E
E
0.50
1.5
10
1.0 2
05
0.50
1
1
3
5
,
?
1.02
,
1
0.50
3
5
Operative
0
.
1
35
Stage
Fig. 1. Indhadualplotsof ionized calcium
and lactate (0--0)
in padents undergoing open heart surgery
horizontal baron thex a,asdenotesperiodon bypass;Utangles () Indicate
when a unit of bloodwas transfused;
wtlcal line shows when calciumwas
administered. Each unit of blood had 1 g of calciumadded
(-)
association
between
these two variables,
which is supported
statistically
by positive correlation
coefficients in 12 of the
16 patients,
and a significant
positive combined estimate of
within-patient
correlation
(r = O.55,p <0.01). Furthermore,
a test for heterogeneity
of within-patient
correlations
did
not approach statistical significance (p <0.25).
Table 1 summarizes the mean changes in calcium, lactate, pH, and hematocrit at each stage of the operation,
along with the correlation
coefficients between ionized calcium and lactate among patients.
Despite hemodilution,
as
indicated
by the generally
declining
hematocrit
values and
decreasing
concentrations
of albumin
(not shown) throughout surgery,
ionized
calcium
decreased
only slightly
between operative
Stages 1 and 2, and then increased
during
Stages 2 through
5. Similarly,
lactate increased across all
stages of surgery. These linear trends in ionized calcium and
lactate
show high statistical
significance
(p <0.01)
and
contrast
markedly with fluctuations
in temperature-corrected pH, which reflect mild alkalemia
in Stages 2-4 and slight
acidosis in Stage 5; they also differ from the pattern for total
calcium,
which is relatively
low in Stages 2-4 and then
increases dramatically concurrent
with infusion of calcium
in Stage 5. The ratio of ionized calcium to total calcium is
significantly
increased
in Stages 3 and 4 relative to Stages 1
and 2 (p <0.001),
coincident
with the increasing
ionized
calcium
and declining total calcium.
Ionized calcium
correlated
well with lactate among the
patients represented
at every stage, but especially
at Stage
five after patients
had been weaned
from bypass and calcium was administered
(Table
1). Because
of the strong
correlation
at stage five, we looked at changes,
by patient, in
Table
1. Mea n (± SD) Changes
in Caiciu m, Lactate,
a nd Other
Variables,
by Stag e of the Operation
Correlation
(and p value)
Calcium
Operative
stage
ionized
No.
patients
1
16
2
3
4
5
15
0.95
0.89
0.98
1.04
1.15
15
9
14
Of iOfliZOd
Total
(0.12)
(0.09)
(0.10)
(0.33)
(0.36)
mmoIIL
2.01
1.85
1.62
1.77
2.26
Ratio, %
47.1 (4.6)
48.1 (4.0)
60.4 (3.3)
58.6 (3.0)
51.1 (6.8)
(0.13)
(0.11)
(0.15)
(0.59)
(0.65)
ionized
calcium
and lactate that resulted
from the initial
administration
of calcium.
The data in Table 2 indicate that,
in all but three of the 16 patients,
the changes in ionized
calcium and lactate
were in the same direction. Four
patients
showed a concurrent
decrease in ionized
calcium
and increase
in total calcium,
probably
because of excess
citrate in blood products
they received,
as discussed
later.
Table 3 shows results of the analysis
of covariance
of
ionized calcium, with patients and operative
stages used as
b4Cai
4-5
-0.13
-0.2
+0.27
+0.65
+ 1.06
-0.29
+0.82
-0.04
+0.54
+0.09
+0.37
+0.01
+0.12
+0.31
+ 0.08
4-5
3-5
3-5
3-4
4-5
4-5
4-5
3
3-5
3-5
3-5
4-5
2-3
4-5
pH
mmol/L
0.99 (0.55)
1.34 (0.71)
1.63 (0.68)
2.36 (1.37)
2.34 (1.45)
7.39
7.43
7.49
7.44
7.35
(0.04)
(0.03)
(0.07)
(0.07)
(0.05)
calcium with
%
38.2
32.3
19.3
18.3
23.1
(4.5)
(2.8)
(2.7)
(2.0)
(3.7)
lactate
.60
.66
.47
.77
.81
(<.01)
(<.01)
(<.08)
(<.01)
(<.001)
-0.1
-0.3
+0.5
+2.3
factors
and hematocrit,
pH, and lactate as
As expected, there is significant
variability
in
ionized calcium among patients and across operative stages,
as indicated
by the statisticalsignificance of the corresponding mean squares. Notably,
the linear regression of ionized
calcium
on lactate
is highly
significant
(p <0.0001),
even
after allowance
for the average
effects of patients
and
operative stages, as well as adjustment
for linear
regression
of ionized
calcium
on pH and hematocrit.
Furthermore,
variability
due to heterogeneity
of the regression
of ionized
calcium on lactate
does not reach statistical significance (p
<0.16), indicating that a single regression
line is adequate.
Based upon
the estimated regression
coefficient,
for the
average patient studied with pH and hematocrit
held constant at their mean values, each millimole
per liter increase
in lactate
is associated with an approximately
0.1 mmol/L
increase in ionized calcium.
A few patients
exhibited
substantial
increases
in both
lactate and ionized calcium
after transfusion
of blood prod-
-08
+0:5
+0.6
+ 1.2
+0.5
-0.5
ucts in operative
Stage 4 (Figure
1). To determine
if these
post-transfusion
data from Stages 4 and 5 may have produced a fortuitous
relationship
between ionized calcium and
lactate, we examined
separately
the pre-transfusion
data of
Stages 1-3, using the same analysis
of covariance
format
of
Table 3. This analysis
corroborated
the significant
regres-
+02
sion (p <0.02)
of ionized
calcium
and lactate,
even after
adjustment
for the covariables
hematocrit
and pH (Table 3).
Table 2. Changes In ionized Calcium and Lactate
(mmoi/L) In 15 Patients after the Initial Administration
of Calcium
Stages
Hematocrit,
Lactate,
[Lact]
+ 1
:
classification
covariables.
-0.4
Discussion
Table 3. Analysis of Covariance
Patients Undergoing
Coronary
Open-Heart
Source of variation
Bypass surgery
Among patients
Among operative stages
Covariables:
Hematocrit
pH
Lactic acid
Heterogeneity
of regressiona
Error
Open-heart surgery
Among patients
Among operative
Covariables:
Hematocrit
pH
Lactic acid
Heterogeneity of
Error
a Variation owing to
(measured
stages
regression
heterogeneity
lactic acid among patients.
of ionized
Bypass
Surgery
Calcium
in
Surgery
or
Degrees of
freedom
square
Significance
(p value)
15
4
0.98
2.33
0.001
1
1
4.33
2.76
1
9.41
Mean
15
0.49
31
0.32
before transfusion)
15
0.30
2
0.38
0.83
1
1
1
15
0.05
10
0.10
0.02
0.83
0.01
0.001
0.01
0.0001
0.16
0.05
0.06
0.02
0.71
0.02
0.92
of the regression of ionized calcium on
Our study shows that changes
in lactate concentrations
in
patients
undergoing
open-heart
surgery
with heart-lung
bypass correlate significantly with ionized calcium, both
before and (especially)
after coadministration
of calcium
with protamine
or citrated
blood. Mean values for both
ionized
calcium
and lactate
showed generally
linear increases during surgery despite hemodilution
and fluctuating pH, whereas total calcium
remained low until the postbypass operative
Stage 5, when exogenous
calcium
and
blood products
typically
were infused (Table 1). Correlations
between
ionized calcium
and lactate
among
patients
were
positive
and statistically
significant
(p <0.05), or nearly
so,
at every stage of open-heart
surgery (Table 1), and withinpatient correlations
were positive in most patients. Results
of the analysis
of covariance
across all patients and operative stages showed that the linear regression
of ionized
calcium on lactate remained
at an extremely
high level of
significance
(p <0.0001),
even after adjustment
for amongand within-patient
variability
as well as correction
for
effects of possible confounding
factors such as pH and
hemodilution
(Table 3).
Data published
by Aloia
et al. (13) reveal a significant
correlation
between
average concentrations
of ionized calcium and lactate
during exercise-induced
mild hypercalcemia.
CLINICAL CHEMISTRY,
Vol. 32, No. 10, 1986
1851
However,
these authors
did not discuss this relationship,
and concluded that hemoconcentration
was responsible
for
the increased
ionized calcium,
although
other studies (19,
20) have shown that hemoconcentration
per se has little
effect on ionized calcium. In another such study (12), similar
changes
in ionized
calcium
and lactate
were observed.
Although
these authors (12) concluded that the concurrent
decrease in blood pH was partly the cause of the increase
in
ionized calcium, their results indicated
that some other in
vivo factor may have contributed
to this increase.
In the current
study, we also observed
a significant
relationship
between
calcium
and lactate,
both across all
operative
stages (p <0.001
in Table 3) and for Stages 1-3,
before any calcium or blood products were administered
(p
<0.02 in Table 3). However,
we demonstrated
by an analysis of covariance that this relationship
cannot be accounted
for solely by change in pH or hemodilution,
suggesting that
lactate may facilitate
an increase in ionized calcium,
or vice
versa. Further,
examination
of the value for ionized calcium
and lactate,
as well as the ratios of ionized to total calcium,
shows that substantial
average increases
occurred
in all of
these variables
during
open-heart
surgery
prior to administration of calcium
or transfusion
of citrated blood products
(Table 1). These data therefore
provide evidence that calcium homeostasis
is altered
by lactate production,
or vice
versa, relatively
independent
of pH or hemodilution.
Several
reports
indicate
that administration
of calcium
may enhance
oxygen consumption,
which could lead to
tissue hypoxia
and, consequently,
an increase
in production
of lactate.
Infusion of calcium
increases cardiac stroke work,
thus increasing
oxygen
demand (14). Because calcium
ions
also have a role in triggering
glycogenolysis
(21), calcium
may influence the production
of lactate through
its effect on
energy utilization
during muscle contraction.
At least two
groups of investigators
have reported
the occurrence
of
tissue necrosis localized at the site of calcium
injection
in
neonates
(22, 23). The mechanism
of the necrosis
was not
known, but calcium
was believed to be the causative
agent.
In our study, calcium
was given
by bolus injection,
usually near the end of the surgical
procedure.
As shown in
Table 2, the direction
of change in lactate
and ionized
calcium was the same in 12 of the 15 patients from whom
samples
were collected before and after calcium administration. These results,
coupled with the highly
significant
correlation
between ionized calcium and lactate at Stage 5
after infusion of calcium (r = 0.81, p <0.001),
suggest that
administration
of calcium
somehow accentuated the association between
these variables.
As patients are weaned from
cardiopulmonary
bypass at Stage 4, the myocardium
is in a
weakly
contractile
state, which may lead to inadequate
tissue perfusion, hypoxia, and production
of lactate. Because
the patient is usually mildly hypocalcemic,
calcium
is given
to improve
hemodynamic
function,
thereby
creating
an
increased
demand
for oxygen,
which could lead to the
increased production
of lactate. However, other mechanisms
are also plausible.
For example,
the warming
of patients
after bypass coincided with the administration
of calcium.
Warming
can lead to an increased production
of lactate,
so
this may explain,
at least in part, the enhanced
correlation
between ionized calcium
and lactate. Another possible interpretation
involves
the ischemic
conditions
of the heart
during
bypass. A considerable
accumulation
of myocardial
lactate could result from cardioplegia
and be introduced
into
circulation
upon reactivation
of the heart and weaning
from
the heart-lung
machine in the same time frame as calcium
administration.
This scenario could produce concurrent
spu1852
CLINICAL CHEMISTRY, Vol. 32, No. 10, 1986
increases in both variables.
However,
contradictory
to
the latter two proposed mechanisms
are that four patients
showed decreases in both ionized calcium and lactate during
Stage 4, and that ionized calcium and lactate were significantly related
(p <0.02)
before any calcium or blood products were administered.
Most of our patients
received citrated
blood products
to
counterbalance
their hemodilute
state, typically after weaning from the heart-lung
bypass pump. As noted previously,
four patients had a concurrent
decrease in ionized calcium
and lactate,
with an increase in total calcium,
during
transfusion
of blood products. This probably
is ascribable
to
an excess of citrate in some units of blood, which would bind
calcium when transfused.
Based on our results, hemodilution
or changes in pH, or
both, cannot readily
be advanced
as explanation
of the
observed
pattern
of ionized calcium. Even though no calcium was given in Stages 1-3, ionized calcium
increased
despite decreases in albumin,
hematocrit,
and total calcium
and a corresponding
increase
in pH. While it is tempting
to
explain
this increase in ionized
calcium
as being due to
parathyrin-induced
release of calcium
from bone, parathyrin apparently
does not rapidly
increase
concentrations
of
ionized calcium
in blood (24,25).
If the affinity between
albumin
and calcium
could be
decreased
during
hypocalcemia,
it would be a mechanism
to
quickly
offset
hypocalcemia,
as has been speculated
before
(25-27).
The association
that we observed between lactate
and ionized calcium
is consistent
with the hypothesis
that
lactate
alters this affinity. Further
investigations
need to
focus on this relationship
by measuring
ultrafllterable
calcium in order
to calculate the protein-bound
calcium
and
determine
if the association
constant between calcium and
albumin
changes during
conditions
of hypocalcemia
and
lactate production.
rious
References
1. Gray it, Braunstein
homeostasis
during
G, Krutzik
coronary
S, Conidin C, MatloffJ.
Calcium
bypass
surgery.
Circulation
1980;62:157-61.
2. Yoshioka K, Tsuchioka
H, Abe T, lyomasa Y. Changes in ionized
and total calcium concentrations in serum and urine during open
heart surgery. Biochem Med 1978;20:135-43.
3. Chambers DJ, Dunham J, Braimbridge
MV, Slavin B, Quiney J,
Chayen
J. The effect of ionized calcium,
pH, and temperature
on
bioactive
parathyroid
hormone during and after open-heart
operations.Ann Thorac Surg 1983;36:306-13.
4. Catinella
FP, Cunningham
JN, Strauss ED, Adams PX, Laschinger JC, Spencer
FC. Variations
in total
and ionized calcium
during cardiac surgery. J Cardiovasc Surg 1983;24:593-602.
5. Stulz PM, Scheidegger D, Drop LI, Lowenstein
E, Layer
MB.
Ventricular
pump performance during hypocalcemia. J Thorac
Cardiovasc Surg 1979;78:185-94.
6. Auffant RA, Downs JB, Amick it. Ionized calcium concentration
and cardiovascular
function
after cardiopulmonary
bypass. Arch
Surg 1981;116:1072-6.
7. Moffitt EA, Tarhan 5, Goldsmith ES, Pluth JR. McGoon DC.
Patterns of total and ionized calcium and other electrolytes in
plasma during and aftercardiac surgery.J Thorac Cardiovasc Surg
1973;65:751-7.
8. AbbOtt
TR. Changes in serum calcium fractions
and citrate
concentrations
during
massive
blood
transfusions and cardiopulmonary bypass. Br J Anaesth 1983;55:753-9.
9. Coetzee AR, van der Merwe WL, Taljaard JJF, Els D. The effect
of acute haemodilution
during
cardiopulmonary
bypass on blood
calcium,
pH, phosphorus,
and protein
values.
S Afr Med J
1983;64:613-7.
10. Heining
during
MPD, Linton RAF, Band DM. Plasma ionizedcalcium
surgery. Anaesthesia
1985;40:237-41.
open-heart
11. Schiavello R, Cavaliers F, Sollazzi L, Loffreda
C, Marana
E.
Changes of serum pyruvate
and lactate in open-heart
surgery.
Resuscitation 1984;11:35-45.
12. Nielsen SP, Christiansen TF, Hartling
0, Trap-Jensen
J.
Increase in serum ionized calcium during exercise.
Clin Sci Mol
Med 1977;53:579-586.
13. Aloia JF, Rasulo P, Deftos LI, Vaswani A, Yeh JK. Exerciseinduced hypercalcemia
and the calciotropic hormones. J Lab Clin
Med 1985;106:229-32.
14. Gefen GA, Drop LI, O’Keefe DD, Rosenthal SV, Newell JB,
Jacocks MA, Daggett
WM. Global
and regional function in the
regionally
ischaemic left ventricle related to plasma ionized calcium. Cardiovasc
Res 1983;17:415-26.
15. Yosowitz
P, Ekiand DA, Shaw RC, Parsons RW. Peripheral
intravenous
infiltration
necrosis.Ann Surg 1975;182:553-6.
16. Toffaletti J, Gitelman HJ, Savory J. Separation
and quantitation of serum constituents
associated with calcium by gel ifitration.
Cliii Chem 1976;22:1968-72.
17. Kelman GR, Nunn JF. Nomograms for correction of blood P02,
PCO2, pH and base excess for time and temperatures.
J Appl
Physiol 1966;21:1484.
18. Snedecor GW, Cochran WG. Statistical methods. Ames: Iowa
State Univ. Press, 1967:429-46.
19. Renoe BW, McDonald JM, Ladenson JH. Influence of posture
on free calcium and related variables. Cliii Chem 1979;25:1766-9.
20. Renoe BW, McDonald JM, Ladenson JR. The effects of stasis
with and without exercise on free calcium, various cations,
and
related parameters. Cliii Chiun Acta 1980;103:91-100.
21. Ebashi S, Endo M. Calcium
ion and muscle contraction
[Review]. Progr Biophys Mol Biol 1968;18:123-83.
22. Weiss Y, Ackerman
C, Schmilovitz L. Localized necrosis of
scalp in neonates due to calcium gluconate
infusion:
a cautionary
note. Pediatrics 1975;56:1084-6.
23. Book LS, Herbst JJ, Stewart D. Hazards of calcium gluconate
therapy in the newborn infant: intra-arterial
injection producing
intestinal necrosisin rabbit ileum. J Pediatr 1978;92:793-7.
24. Law WM Jr, Heath H ifi. Time- and dose-related biphasic
effects of synthetic bovine parathyroid hormone fragment
1-34 on
urinary cation excretion. J Clin Endocrinol Metab 1984;58:606-8.
25. Toffaletti J, Nissenson R, Endres D, McGariy E, Mogollon G.
Influence of continuous infusion of citrate on responses of immunoreactive parathyroid
hormone, calcium and magnesium
components, and other electrolytes in normal adults during platelet
apheresis. J Clin Endocrinol Metab 1985;60:874-9.
26. Ladenson JH, Lewis JW, McDonald JM, Slatopolsky E, Boyd
JC. Relationship of free and total calcium in hypercalcemic
conditions. J Clin Endocrinol Metab 1979;48:393-7.
27. Toffaletti
J. Changes in protein-bound,
complex-bound, and
ionized calcium related to parathyroid hormone levels in healthy
donors during platelet apheresis. Transfusion 1983;23:471-5.
CLINICAL CHEMISTRY,
Vol. 32, No. 10, 1986
1853