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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 26, No 6, November/December 2015
AFRICA
239
release of biochemical cardiac markers during CABG surgery
accompanied by CPB were investigated using histopathological
examinations and biochemical measurements.
Although optimal current myocardial protective techniques
were applied during surgery in all study populations, our
histopathological results revealed that CABG surgery
accompanied by CPB and ACC led to slight-to-moderate
PMI as well as moderate-to-severe myocardial apoptosis in
all cases. Apoptosis is considered one of the mechanisms of
cardiomyocyte loss during CPB and cardioplegic arrest during
CABG surgery.
19,20
Myocardial apoptosis is induced immediately
after cardioplegic arrest and CPB.
21
Apoptosis during CPB and cardioplegic arrest can be induced
by several mechanisms, including I/R injury and the release
of cytokines and inflammatory factors.
20,22
Previous studies
have reported that cardioplegic cardiac arrest could stimulate
pro-inflammatory cytokines, induce cardiomyocytic apoptosis,
and impair postoperative cardiac performance.
23,24
In our study,
a positive correlation was found between myocardial apoptotic
index and ACC or CPB time. Schmitt
et al
. and Ruifrok
et
al
. found a positive correlation between the apoptotic index
and duration of ACC and CPB, which was consistent with
our study.
25,26
Conversely, Wu
et al
. reported that myocardial
apoptosis showed no correlation with ACC and CPB time.
27
We observed significant increases in CK-MB, CK-MB mass,
cTnI and hscTnT levels within 15 minutes of the reperfusion
period. The concentrations of coronary sinus CK-MB, CK-MB
mass, cTnI and hscTnT were higher than the corresponding
arterial concentrations after aortic declamping, indicating
considerable myocardial release of these markers after
reperfusion. In addition, we found significant myocardial net
release of CK-MB, CK-MB mass, cTnI and hs-cTnT into the
coronary circulation after aortic declamping within 15 minutes
of reperfusion. Myocardial net release of CK-MB, CK-MB mass,
cTnI and hscTnT indicated that myocardial damage had occurred
during ACC and cardioplegic cardiac arrest, as well as a very
rapid release from the myocardium with the onset of reperfusion.
Although cardiac troponins are structurally bound proteins
of striated muscles, the cytosolic pool of cTnT and cTnI may
account for the rapid early myocardial release in parallel with
CK-MB and CK-MB mass.
28
Coronary sinus sampling allows
direct sampling of the blood draining the heart, therefore the
arteriovenous difference provides the closest correlation between
cardiac marker release and ischaemic time.
These data obtained during CABG are in accordance with
the results of previous studies.
29,30
Bleier
et al
. found significant
myocardial net release of CK-MB mass, cTnT and cTnI into the
coronary circulation after aortic declamping within 20 minutes
of reperfusion.
29
Koh
et al
. reported that cTnT concentrations
increased in every patient after aortic declamping, and were
higher in coronary sinus blood than in arterial blood, indicating
net myocardial release of troponin T during the period of
reperfusion.
30
Despite the fact that a positive correlation was found between
myocardial apoptotic index and CK-MBmass, cTnI and hs-cTnT
concentrations, as well as a positive correlation between degree
of myocardial injury and cTnI and hs-cTnT concentrations
after aortic declamping, the strongest correlation was observed
between hs-cTnT and myocardial apoptosis and injury. In a
previous study, myocardial biochemical markers demonstrated
no correlation with myocardial apoptosis, unlike in our study.
27
When we examined the relationship between myocardial
apoptosis and net release of cardiac markers, a significant
positive correlation was found between apoptosis and net release
of hs-cTnT after reperfusion. A positive correlation was observed
between degree of myocardial injury and net release of cTnI and
hs-cTnT, but hs-cTnT demonstrated a stronger correlation with
myocardial injury than cTnI after aortic declamping.
We also examined the relationship between ACC and CPB
time and net release of cardiac markers. Duration of ischaemic
time, which is expected to be a strong predictor of release of
biochemical markers, correlated with net release of hs-cTnT but
not with that of CK-MB, CK-MB mass and cTnI. In several
previous studies, net cTnT release and peak cTnT concentrations
were correlated with ACC time, which was consistent with our
study.
30,31
Cardiac troponins are highly specific markers of cardiac
myocyte damage and seem to better indicate myocardial injury
occurring during CABG surgery.
32-34
High-sensitivity troponin
assays have recently been developed, being more sensitive than
contemporary assays at detecting lower troponin levels. The
high-sensitivity troponin T assay has lowered the detection
threshold for myocardial necrosis and therefore permits more
rapid diagnosis of MI.
35,36
Recently, several studies have been reported related to the
ability of hs-cTnT to diagnose PMI after CABG or non-cardiac
surgery.
37,38
Wang
et al
. reported that post-operative hs-cTnT
Table 6. The relationship between apoptotic index (TUNEL),
histopathological myocardial injury score and ACC time,
CPB time and graft number
ACC time
(min)
CBP time
(min)
Number of
grafted vessel
Apoptotic index
(TUNEL)
r
=
0.876
p
<
0.001*
r
=
0.694
p
<
0.001*
r
=
0.445
p
=
0.007*
Myocardial
injury score
r
=
0.867
p
<
0.001*
r
=
0.725
p
<
0.001*
r
=
0.555
p
<
0.001*
ACC: aortic cross-clamping; CPB: cardiopulmonary bypass;
TUNEL: terminal deoxynucleotidyl transferase-mediated deoxyuri-
dine triphosphate nick end-labelling. Relationships between data were
tested using Spearman’s correlation analysis. *A
p
-value
<
0.05 was
considered statistically significant.
Table 7. The relationship between net release of cardiac
marker values and intra-operative data in the post-ACC period
Net release of
cardiac markers
ACC time
(min)
CPB time
(min)
Number of
grafted vessel
CK-MB (U/l)
r
=
0.110
p
=
0.529
r
=
0.187
p
=
0.280
r
=
0.128
p
=
0.448
CK-MB mass
(
µ
g/l)
r
=
0.110
p
=
0.526
r
=
0.155
p
=
0.374
r
=
–0.015
p
=
0.931
cTnI (
µ
g/l)
r
=
0.157
p
=
0.366
r
=
0.121
p
=
0.489
r
=
0.052
p
=
0.759
hs-cTnT (ng/l)
r
=
0.448
p
=
0.007*
r
=
0.342
p
=
0.047*
r
=
0.200
p
=
0.249
ACC: aortic cross-clamping; CPB: cardiopulmonary bypass; CK-MB:
creatine kinase isoenzyme MB; cTnI: cardiac troponin I; hs-cTnT:
high-sensitivity cardiac troponin T; post-ACC: within 15 minutes of
aortic declamping. Net release of cardiac markers was quantified as
arteriovenous difference (coronary sinus concentration minus arterial
concentration). Relationships between data were tested using Spear-
man’s correlation analysis. *A
p-
value
<
0.05 was considered statisti-
cally significant.