CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 8, September 2013
324
AFRICA
Discussion
The main purpose of the current study was to investigate the
preventive effects of LA on ECC-triggered inflammatory events.
We systematically investigated the generation of pro-inflammatory
cytokines IL-6 and IL-8, and ASO, CRP and haptoglobulin
after ECC. Recent studies on inflammatory reactions occurring
during and after CPB have improved our understanding of the
contribution of inflammatory pathways to disease.
Our results clearly demonstrate that ECC triggered a
pro-inflammatory cytokine release during CPB, which was
significantly inhibited by LA administration into the ECC
circuit. Warren
et al.
found that contact of the patient’s blood
with the artificial surfaces of the ECC circuit triggered a
systemic inflammatory response related to increased secretion
of IL-1
β
, IL-6 and IL-8.
4
The inflammatory response is associated with the production
of reactive oxygen species (ROS). The primary source of
ROS during ECC is thought to be neutrophil granulocytes,
11
which also release enzymes. ECC activates neutrophil
granulocytes,
12
which then trigger an inflammatory response
with complement activation after cytokine release. This may
stimulate further cardiac injury.
13
The activation of neutrophil
granulocytes may occur following complement activation by
both immunological or non-immunological (heparin-protamine,
endotoxin) pathways.
14
Up-regulation of adhesion molecules
may be stimulated by cytokines on the cardiac cells, which allow
neutrophil granulocytes to discharge ROS products.
15
More recently, Salinthone
et al.
have shown that LA displays a
non-redox anti-inflammatory role
16
by moderating a diverse range
of signaling cascades, which mediate these processes. Moreover,
LA induces the production of the immunomodulator cAMP in
human inflammatory cells by activating the prostaglandin E2
(PGE2), EP2 and EP4 receptors.
17
In addition, in Wang and
co-workers’ ECC model for CPB, the myocardium produced
inflammatory mediators and ROS during ischaemia–reperfusion,
which would contribute to cardiac functional reduction and
apoptosis.
18
Similarly, Sawa
et al
. reported that cardiac myocytes exposed
Fig. 2. ECC with LA treatment had a significant effect on activation of C3 (A) and C4 (B) release. *
p
<
0.05 indicates
statistical significance versus the respective baseline value in each group.
#
p
<
0.05 indicates statistical significance
between the two groups at each time point.
0.5
0.4
0.3
0.2
0.1
0.0
P1
P2
P3
P4
P5
Time periods
C4 (g/l)
Control
LA
*
*
#
#
#
#
B
2.0
1.5
1.0
0.5
0.0
P1
P2
P3
P4
P5
Time periods
C3 (g/l)
Control
LA
*
*
*
*
* *
#
#
#
A
*
*
*
*
*
*
*
*
Fig. 3. C-reactive protein (CRP) in serum analysed using
a turbidimetric method. *
p
<
0.05 indicates statistical
significance versus the respective baseline value in each
group.
#
p
<
0.05 indicates statistical significance between
the two groups at each time point.
200
180
160
140
120
100
80
60
40
20
0
P1
P2
P3
P4
P5
Time periods
CRP (mg/l)
Control
LA
*
*
#
*
*
#
Fig. 4. Haptogloubulin levels in the serum were analysed
using a turbidimetric method. *
p
<
0.05 indicates statisti-
cal significance versus the respective baseline value in
each group.
#
p
<
0.05 indicates statistical significance
between the two groups at each time point.
3.0
2.5
2.0
1.5
1.0
0.5
0.0
P1
P2
P3
P4
P5
Time periods
Haptoglobulin (g/l)
Control
LA
*
*
*
*
#
#
*
*
#
