CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 8, September 2013
322
AFRICA
Alpha lipoic acid attenuates inflammatory response
during extracorporeal circulation
IHSAN SAMI UYAR, SULEYMAN ONAL, M BESIR AKPINAR, IBAK GONEN, VEYSEL SAHIN,
ABDULHADI CIHANGIR UGUZ, OKTAY BURMA
Abstract
Aim:
Extracorporeal circulation (ECC) of blood during cardi-
opulmonary surgery has been shown to stimulate various pro-
inflammatory molecules such as cytokines and chemokines.
The biochemical oxidation/reduction pathways of
a
-lipoic
acid suggest that it may have antioxidant properties.
Methods:
In this study we aimed to evaluate only patients
with coronary heart disease and those planned for coronary
artery bypass graft operation. Blood samples were obtained
from the patients before the operation (P1) and one (P2),
four (P3), 24 (P4) and 48 hours (P5) after administration
of
a
-lipoic acid (LA). The patients were divided into two
groups, control and LA treatment group. Levels of interleu-
kin-6 (IL-6) and -8 (IL-8), complement 3 (C3) and 4 (C4),
anti-streptolysin (ASO), C-reactive protein (CRP) and hapto-
globin were assessed in the blood samples.
Results:
Cytokine IL-6 and IL-8 levels were significantly
higher after surgery. Compared with the control groups, LA
significantly decreased IL-6 and IL-8 levels in a time-depend-
ent manner. CRP levels did not show significant variation
in the first three time periods. CRP levels were higher after
surgery, especially in the later periods. These results demon-
strate that CRP formation depends on cytokine release. C3
and C4 levels were significantly higher after surgery than in
the pre-operative period. LA treatment decreased C3 and C4
levels. Therefore, LA administration may be useful for the
treatment of diseases and processes where excessive cytokine
release could cause oxidative damage.
Conclusions
: Our findings suggest a possible benefit of using
LA during cardiac surgery to reduce cytokine levels.
Keywords:
extracorporeal circulation, systemic inflammatory
response, oxidative stress,
a
-lipoic acid
Submitted 2/6/13, accepted 4/9/13
Cardiovasc J Afr
2013;
24
: 322–326
DOI: 10.5830/CVJA-2013-067
Nowadays, extracorporeal circulation (ECC) is commonly
employed by surgeons in many cardiac surgical procedures, with
the aim of keeping patients’ circulatory parameters at steady
levels. ECC is therefore a vital tool for good execution of cardiac
surgery.
However, ECC is also associated with some disadvantages.
The immune system generates a systemic inflammatory response
to the artificial surfaces of the ECC circuit.
1
ECC-related
inflammation can result in adverse effects, including dysfunction
of the myocardium, lung, kidney and liver, which may cause
multi-organ failure, stroke and significant death rates.
2-4
The
molecular mechanism of ECC-induced inflammation needs
clarification.
2
Inflammation is a defensive mechanism of vascularised
tissue, which functions as part of the normal host inspection
mechanisms to destroy or quarantine both harmful agents and
damaged tissue resulting from physiological processes.
5
As a
result of inflammation, levels of different cytokines either rise
or fall. These changes in cytokine levels and activation of the
complement system are well-known parameters used in the
laboratory to determine the inflammatory response.
α
-Lipoic acid (LA) is an essential antioxidant that plays a
crucial role in the mitochondrial respiratory pathway, including
dehydrogenase reactions. It acts with reactive oxygen species
(ROS) such as hydroxyl, peroxyl and superoxide radicals and
also protects the cellular membrane structure by interacting
with glutathione (GSH), which is the preferred substrate of
vitamin E.
6,7
The biochemical oxidation/reduction pathways of
LA suggest that it may have potent antioxidant properties.
Cardiopulmonary bypass (CPB) -triggered systemic
inflammatory response is associated with increased cytokine
levels, namely interleukin-6 (IL-6) and interleukin-8 (IL-8).
These cytokines may be responsible for many undesirable
sequelae associated with CPB.
8
The main target of our current study was to investigate
whether LA administration could modulate the ECC-triggered
inflammatory response during
ex vivo
ECC. Standard procedures
were used and 1 200 mg LA was administered into the ECC
circuit. The effects of LA on IL-6, IL-8, ASO, CRP and
haptoglobulin release were investigated.
Methods
The study protocol was approved by the ethics committee of
the Faculty of Medicine, Firat University, and it adheres to
Department of Cardiothoracic Surgery, Faculty of Medicine,
Şifa University, İzmir, Turkey
IHSAN SAMI UYAR, MD,
M BESIR AKPINAR, MD
VEYSEL SAHIN, MD
ABDULHADI, MD
Department of Microbiology, Faculty of Medicine, Suleyman
Demirel University, Isparta, Turkey
SULEYMAN ONAL, MD
Department of Infectious Diseases, Faculty of Medicine,
Suleyman Demirel University, Isparta, Turkey
IBAK GONEN, MD
Department of Biophysics, Faculty of Medicine, Suleyman
Demirel University, Isparta, Turkey
ABDULHADI CIHANGIR UGUZ, MD
Department of Cardiothoracic Surgery, Faculty of Medicine,
Firat University, Elazig, Turkey
OKTAY BURMA, MD
