1. BACKGROUND
Coronary artery disease (CAD), which is one of the most common causes of
mortality and morbidity all over the world, has many pathophysiological
causes and consequences. Reactive oxygen species (ROS) and oxidative
stress have negative effects on processes such as the development and
acceleration of CAD and plaque formation.1,2 In
particular, ROS, which is formed by the deterioration of molecular and
cellular functions, causes oxidative damage above physiological
levels.3 High oxidative stress, which occurs as a
result of decreased antioxidants and increased oxidants together with
inflammation, has a synergistic effect on the standard risk factors of
CAD.4 The synergistic effect induced by the low
antioxidant level and the high oxidant status leads to the initiation of
inflammatory cascades and oxidation of low-density lipoprotein (LDL).
Subsequent processes lead to the formation of foam cells from
macrophages, differentiation of vascular smooth muscle cells, activation
of vascular matrix metalloproteinases, and disruption of the
extracellular matrix of the affected area.5-7 This
situation has irreversible consequences for CAD. Therefore, the delicate
balance between oxidants and antioxidants is vital in these processes.
The main goal in ROS-mediated biochemical reactions is not to create
oxidative stress, but to try to maintain and restore ”redox
homeostasis”.8 Thiol/disulfide level has critical
importance in maintaining and maintaining plasma and intracellular redox
homeostasis.8,9 Thiols, which are the main factor in
ensuring the redox balance, have a high sensitivity to oxidation due to
the -SH (1 sulfur and 1 hydrogen atom) groups in their structures and
interact with almost all physiological oxidants. Because of these
properties, they are considered ”essential antioxidant
buffers”.9-12 In addition to their antioxidant
properties, they play a role in many biochemical events such as
regulation of protein functions, signal transduction, regulation of
transcription factors, and immune response.12-14Disulfides, the oxidized form of thiols, are redox-sensitive covalent
bonds formed between two thiol groups (sulphydryl atom). Disulfide bond
structures formed by ROS oxidation can revert to thiol groups and thus
maintain the thiol/disulfide balance. The thiol/disulfide ratio is a new
marker used as a measure of thiol and disulfide homeostasis.
Thiol/disulfide levels change significantly in the pathogenesis of
cardiovascular diseases, diabetes, cancer, and renal
failure.9
The N-terminal amino end of the albumin molecule, which is an important
source of thiol and accepted as the thiol pool of the plasma, is the
binding site of metal ions such as Co+2,
Ni+2, and Cu+2. In oxidative stress,
which occurs in many different conditions such as acidosis, hypoxia, and
exposure to free iron and copper, the N-terminus of albumin is modified
and its ion-binding ability decreases.15 This modified
form of albumin is called ischemia-modified albumin
(IMA).16 In various coronary syndromes, ischemia,
acidosis, hypoxia, and ROS increase caused by decreased coronary blood
flow lead to albumin modification and an increase IMA
level.17 IMA levels, which increase in a short time in
the early phase of ischemia and in myocardial infarction, are used as a
cardiac biomarker in clinical practice.18,19 IMA,
which reflects myocardial ischemia within minutes, shows the degree of
short-term oxidative effect.20 Sinha et al. reported
that the sensitivity of the IMA level increased to 95% when used
together with electrocardiography and cardiac troponin (cTnT) in acute
coronary syndrome.21
Foreign material surface, hemolysis, surgical procedure, and reperfusion
affect the cellular redox balance in the on-pump coronary artery bypass
grafting (CABG) method, which is used for surgical treatment in CAD and
performed with the help of cardiopulmonary bypass (CPB). In addition,
the high level of molecular oxygen given to the circulatory system
during on-pump CABG creates cellular stress and activates the
inflammatory system. The resulting stress and inflammatory response
affect almost all biochemical reactions by disrupting holistic
homeostasis and causing serious damage.22,23 A shift
in the thiol/disulfide redox balance at this stage can have adverse
systemic consequences. Because most of the redox-sensitive signal chains
respond to changes in the thiol redox state when exposed to
ROS.8 For example, the transcription factor AP-1,
which is directly related to the redox state; regulates inflammatory
gene expression in response to various stimuli, including cytokines,
growth factors, stress, bacterial, and viral
infections.24-26 Nuclear factor-kappa B (NF-κB),
another transcription factor sensitive to the redox state, plays a role
in regulating the expression of many other genes related to cell
survival, proliferation, and differentiation in inflammatory and immune
responses.24, 27 Moreover; Signaling pathways such as
JNK, p38 MAPK, and amplification of immunological functions are also
stimulated according to redox balance.28 Therefore,
detection of thiol/disulfide homeostasis is extremely important in terms
of controlling redox-mediated inflammatory signaling pathways during
on-pump CABG.
Although there are many studies on thiol/disulfide homeostasis, there
are few studies on the relationship between on-pump CABG and
thiol/disulfide homeostasis and IMA levels. In addition, such a study
related to the subject of pericardial fluid has not been found in the
literature. Thanks to this study, it is important to investigate the
thiol/disulfide balance and IMA levels in both the pericardial fluid and
plasma of the same patient (before and after on-pump CABG) in terms of
their secondary effects. In this study, the physiological and
biochemical changes of the heart in terms of thiol/disulfide balance
were investigated by examining the pericardial fluid, which is the
closest tissue fluid to the heart, and gives accurate information about
the heart.
Plasma thiol/disulfide ratio; It can be an easy target for therapeutic
intervention by N-acetylcysteine or other thiol compounds. In order to
control the oxidative stress that may occur during on-pump CABG,
thiol/disulfide homeostasis can be followed to prevent negative
situations that may be caused by stress. For this, many treatment
strategies can be developed, including the addition of antioxidant
substances to the CPB system or intrapericardial drug administration.
In this study, preop and postop thiol/disulfide balance and IMA levels
were compared in the plasma of patients undergoing coronary artery
bypass surgery. In addition, the thiol/disulfide balance and IMA levels
in pericardial fluid were also investigated in this study and their
relationship with plasma was evaluated.