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.