4. COMMENT
During the CPB performed with an on-pump CABG, tissue perfusion and blood pressure deteriorate, blood flow decreases, and ischemia, acidosis, hypoxia, and ROS increase with the effect of foreign material surface.31 Oxidative stress caused by all these multifactorial factors increases myocardial damage, triggers inflammatory processes, limits the success of the surgical procedure, and adversely affects the patient’s survival or recovery time. Therefore, detection of systemic redox hemostasis before and after on-pump CABG is extremely important for the prognosis of the surgical procedure and the disease. The results obtained in the study show that the levels of native thiol, total thiol, and disulfide decrease after an on-pump CABG. These results are important in terms of minimizing the poor prognostic effects of cardioplegia applied during the on-pump CABG procedure and the subsequent reperfusion period.
The non-specific inflammatory response in the CPB process, which creates a foreign environment outside the body with extracorporeal circulation, shows its negative effects from the first minutes.32Cardiac arrest, especially after cardioplegia, causes serious global ischemia in the heart. The increased systemic inflammatory response in this process and the subsequent reperfusion period cause an increase in oxygen-derived free radicals, which can cause myocardial damage and many problems.33 The primary targets of the formed ROS are the -SH groups of sulfur-containing amino acids (cysteine, methionine) in proteins. Reversible disulfide bonds form from -SH groups oxidized by ROS. This is the first indication of radical-mediated protein oxidation. Evidence has shown that there are significant relationships between changes in thiol/disulfide homeostasis and cardiovascular diseases.4,33,34
In some studies, significant positive correlations were found between the peak levels of troponin I—one of the most important cardiac biomarkers—and disulfide levels, disulfide/native thiol, and disulfide/total thiol ratios.1 Altıparmak et al. reported that the native and total thiol levels were significantly decreased in patients with critical coronary artery disease, and these reductions were associated with the severity of coronary artery disease.35 These studies show that low native thiol levels are independent predictors of coronary artery disease.
In this study, albumin and IMA levels increased in plasma samples after CPB compared to pre-CPB, while native thiol, total thiol, and disulfide levels decreased. Significant differences were detected between albumin, IMA, and thiol/disulfide homeostasis parameters measured at different times of CPB. Accordingly, plasma native and total thiol levels decreased due to increased oxidative stress during CPB. In vivo,ROS played an active role in reducing the thiol level, and oxidative conversion and reduction of thiols to disulfides were performed. Under normal conditions, the disulfide level should increase in response to the decreasing native thiol level. However, the opposite was found in our study. The most important reason for this is that the level of disulfides in the CPB system may have decreased due to adherence to the non-endothelial surface and filters. During CPB, especially since capillary permeability is impaired, fluid flows from the vein to the tissues, and the intravascular fluid decreases. Accordingly, plasma albumin density may have increased after CPB.
Decreased myocardial blood flow causes hypoxia, acidosis, increase in reactive oxygen derivatives and changes in serum albumin, thereby increasing the formation of IMA.36 Similarly, in our study, plasma IMA levels increased after CPB. The reason for this may be the modification of albumin levels as a result of ischemia, acidosis, hypoxia and ROS increase for many reasons, including impaired tissue perfusion, decreased blood flow or foreign material surface during CPB. Because even the slightest decrease in blood flow can change the level of IMA.31 A study confirming this information has reported that continuous ventilation during CPB provides benefits for an increase in native and total thiol levels, a decrease in IMA levels, and a shorter hospital stay.31 Continuous ventilation during CPB reportedly reduces ischemia and provides better inspiratory capacity by reducing lung damage.37 Ischemia-modified albumin and redox homeostasis can be controlled by reducing ischemia and hypoxia with correct ventilation and oxygenation procedures during CPB.
Considered an ultrafiltrate of plasma, pericardial fluid is also a transudate released from the cardiac interstitium, reflecting the cardiac interstitium’s composition and the production of macromolecules in the myocardium.38,39 This study is the first in the literature to investigate IMA and thiol/disulfide homeostasis in pericardial fluid, support the view that pericardial fluid is plasma ultrafiltrate and provide important information on the matter. The negative relationship between IMA and thiols in the pericardial fluid indicates the effect of ischemia in the pericardium. Rapidly rising IMA levels are used as a cardiac biomarker in the early phase of ischemia and myocardial infarction.20 Detection of IMA, which reflects ischemia in the myocardium and has a high sensitivity, in the pericardial fluid shows that the pericardial fluid reflects the heart’s subclinical condition in coronary artery diseases. However, it is difficult to measure the degree of subclinical conditions in the heart and their effect on the heart, and there is no clear procedure for treatment.
The relationship between albumin, IMA, and thiol/disulfide homeostasis parameters during and after CPB, postoperative complications and the need for inotropic support has not been clarified. One study reported that thiol levels decreased in acute ischemic strokes and that thiol supplements could reduce neuronal damage associated with stroke and provide recovery. The same study reported that N-acetylcysteine or other thiol providers with antioxidant properties can also be used as a therapeutic intervention in the thiol/disulfide balance.29,40