CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 6, July 2013
228
AFRICA
outcomes. The release of cytokines [tumour necrosis factor-
alpha (TNF-
α
), interleukins and interferons] may negatively
affect cardiac, renal and pulmonary functions.
2
Cytokine release
was shown to correlate with outcome after cardiac surgery.
During and after CPB, serum levels of IL-6, IL-8 and TNF-
α
were increased.
TNF-
α
is a proximal mediator in the inflammatory cascade.
7
It
induces endothelial cells to produce cell adhesion molecules (E-
and P-selectins), which bind to ligands on activated leukocytes to
mediate ‘rolling’ of the leukocytes, and intracellular and vascular
cell adhesion molecules, which facilitate leukocyte migration
from the endothelium to the extravascular space.
1
TNF-
α
also
induces a second wave of cytokines such as IL-6, which is
an important regulator of the hepatic acute-phase response,
and IL-8, a cytokine with important neutrophil-activating and
chemo-attractant properties.
7
The neutrophilic effects of IL-8
lead to local release of proteolytic enzymes, with resultant
pulmonary injury.
8
Increased levels of IL-6 and IL-8 were also related to
regional wall motion abnormalities following on-pump cardiac
surgery.
2
The release of IL-6 and -8 during CPB led to
neutrophil entrapment in pulmonary capillaries. This in turn led
to endothelial cell swelling, plasma and protein extravasation
into the pulmonary interstitial tissue, together with the release of
proteolytic enzymes and the resultant congestion of the alveoli.
9
The clinical result was decreased P
a
O
2
and increased P
a
CO
2
,
indicating pulmonary injury.
10
The negative effects of these cytokines are limited by the
anti-inflammatory cytokine IL-10, which has protective effects
against organ dysfunction following CPB.
11
In a study of 13
patients, Deblier
et al
.
12
reported increased IL-10 release, with
a peak at the end of CPB in both ventilated and non-ventilated
groups, but ventilation did not influence this increase and there
was no significant difference between the groups. They failed
to document a significant increase in IL-6 in both groups.
Beer
et al
.
13
conducted a similar study and indicated that
continued ventilation during CPB attenuated pro-inflammatory
IL-6 concentrations and anti-inflammatory IL-10 concentrations.
The levels of IL-6 and IL-10 peaked at the end of surgery (which
corresponds to T
2
in our study) in both groups.
Ng
et al
.
3
documented higher IL-10 levels one hour after
declamping the aorta in the ventilated group (which corresponds
to sometime between T
1
and T
2
in our study). In our study, the
levels of IL-6 were highest six hours after discontinuation of CPB
in both groups, but there was no significant difference at any time
interval between the ventilated and non-ventilated groups. In the
NV group, IL-10 levels peaked immediately after discontinuation
of CPB, and one hour after discontinuation of CPB in the V
group. The serum IL-10 levels were only significantly higher in
the NV group immediately after discontinuation of CPB.
Miranda
et al
.
7
compared different ventilation strategies
during CPB in their randomised, controlled clinical study:
continuous ventilation, early and open-lung concepts. They
observed that CPB caused a significant increase in IL-6, IL-8
and IL-10 levels. IL-6 levels did not differ significantly between
the groups. The decrease in IL-10 levels was more pronounced
in the early open-lung group. After discontinuation of CPB, they
observed a more rapid decrease in IL-8 in the open-lung groups.
They concluded that the open-lung concept attenuates the
inflammatory response. It is not wise to compare our results with
theirs since the design of the studies were completely different,
but we can conclude that we did not observe an objective
attenuation of the inflammatory response with ventilation.
Most of the studies comparing the effects of ventilation
on the inflammatory response after CPB did not study serum
IL-8 levels.
12,13
IL-8 is a very important cytokine in the
pathophysiology of myocardial ischaemia. Its levels correlate
with complications following myocardial infarction, and anti-
IL-8 antibodies prevented injury in experimental models.
7
Its
levels also correlated well with left ventricular wall motion
abnormalities in the postoperative period.
4
Furthermore, it was
reported that cyclic alveolar stress due to mechanical ventilation
led to increased IL-8 levels.
14
Ng
et al
.
3
studied IL-8 levels. They reported IL-8 levels were
higher in the non-ventilated group four hours after declamping.
In our study, in the ventilated group, we did not observe any
significant change in IL-8 concentrations. They peaked at one
hour after discontinuation of CPB in the non-ventilated group
and then decreased to baseline levels. However, there was no
statistically significant difference between the groups at any
given time interval.
Lamarche
et al
.
15
reported that CPB with reperfusion without
aortic clamping induced a selective decrease in endothelial
relaxation to acetylcholine, and normal ventilation during CPB
prevented changes in endothelium-dependent relaxation of
the endothelium. Similarly Gagnon
et al
.
4
documented that
continued ventilation during CPB correlated with an attenuated
inflammatory and proteolytic process and better preserved
pulmonary function. It was suggested that maintaining ventilation
and pulmonary flow during CPB attenuated the inflammatory
response.
3,5,16
The continuation of pulmonary blood flow during
CPB also led to reduction in serum IL-6 and -8 levels.
10
The lungs depend on three separate sources of oxygen
delivery: bronchial arterial and pulmonary arterial circulations,
and alveolar ventilation.
3
Two of these cease during CPB because
TABLE 3. COMPARISON OF TWO GROUPS BY
POSTOPERATIVEVARIABLES
NV group
(
n
=
29)
mean
±
SD
V group
(
n
=
30)
mean
±
SD
p
-value*
ICU intubation time (h)
9.67
±
3.29
9.27 ± 2.86
0.61
Length of stay
ICU (h)
47.90
±
14.16 45.83
±
2.15
0.43
Postoperative (days)
5.45
±
0.87
6.07
±
1.66
0.08
Drainage tubes removed (h)
36.03
±
9.22 36.93
±
20.64 0.94
Total amount of drainage (ml) 709.66
±
541.21 720.00
±
540.37 0.83
Number of FFP used
1.07
±
2.18
1.10
±
1.34
0.94
Number of packed RBC used 1.79
±
1.67
1.60
±
1.67
0.66
Number of PC used
0.45
±
1.32
0.37
±
1.21
0.80
n
(%)
n
(%)
p
-value**
Postoperative exploration for
haemorrhage
0
1 (3.3)
1.00
Postoperative AF
6 (20.7)
3 (10.0)
0.29
Renal dysfunctiona
5 (17.2)
4 (13.3)
0.73
Postoperative stroke
0
0
-
SD: standard deviation, NV: non-ventilated, V: ventilated, ICU: intensive care
unit, FFP: fresh frozen plasma, RBC: red blood cells, PC: platelet concentrate,
AF: atrial fibrillation.
*Independent samples
t
-test, ** Fisher’s exact test.
a
Defined when peak creatinine value was
≥
1.5 times the pre-operative value.
