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