Coronary artery bypass grafting (CABG) induces oxidative stress (OS). This situation is closely associated with overproduction of reactive oxygen species (ROS). ROS plays an important role in the physiopathogenesis of OS [
However, ROS that have been considered not only as lethal byproducts of cellular metabolism but also as important molecules in vascular signaling are normally present in cells. The production of ROS in the organisms and their degradation by antioxidants is in balance. When ROS exceeds the antioxidant capacity, this situation results in OS [
Serum concentrations of different oxidative components can be measured in the laboratory separately, but the measurement of these molecules is labor intensive and requires much time, complicated techniques, and cost. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) reflect the redox balance between oxidation and antioxidation. TAS measurement is an indicatorof the activity of all antioxidants while TOS is anindicator of ROS. OSI is the ratio of TOS to TAS and an indicator of OS degree [
There are various obstacles to devise appropriate strategies for optimal perioperative antioxidant therapy. Contribution of the various mechanisms on the oxidant-antioxidant balance during on-pump coronary artery bypass grafting (ONCABG) has not been fully evaluated yet [
A total of 23 patients (17 males, 6 females) who underwent elective isolated ONCABG were included in this study. Patients with any of the following criteria were excluded: acute coronary syndrome, emergency surgery, reoperation, combined procedures (e.g., valvular surgery), off-pump coronary artery bypass grafting (OPCAB), as well as patients with chronic inflammatory disease (such as rheumatoid arthritis, malignancy, or psoriasis), with autoimmune disease, or receiving immunosuppressive drugs. None of the patients used vitamins or dietary supplements. Informed consent was obtained from all patients, and approval for the study was given by the local ethics committee (2013-164).
The median aortic cross clamping (XC) time was 42 minutes. We divided the patients into 2 groups according to median XC time. Group 1 consists of 11 patients (8 males, 3 females) with a below median XC time and group 2 consists of 12 patients (9 males, 3 females) with a median and above median XC time.
The same surgical and anesthetic team managed all patients. Patients received premedication with midazolam. Anesthesia was induced with midazolam, fentanyl, thiopental, and rocuronium, while sevoflurane and fentanyl were used as maintenance. Radial and pulmonary arterial catheters were introduced under local anesthesia. After standard general anesthesia, a median sternotomy was performed, followed by routine aortic and right atrial cannulation. Cardiopulmonary bypass (CPB) was carried out using membrane oxygenators and moderate systemic hypothermia. Myocardial protection was achieved by antegrade mild hypothermic (32°C) blood cardioplegia, repeated every 20 min. Heparin 3.0 mg/kg was administered, and the activated clotting time was maintained >400 sec during the procedure. Heparin was neutralized with protamine in a ratio of 1 : 1.3 within 10 minutes after the end of CPB. After surgery, all patients were followed up in the intensive care unit.
Blood samples for TOS and TAS determination were drawn preoperatively, 20 minutes after aortic cross clamping and just before the administration of the second cardioplegia (AC 20 min), and 30 minutes (Rp 30 min), 6 hours (Rp 6 h), and 48 hours (Rp 48 h) after cross clamp release (reperfusion) from the arterial line. The blood samples were kept at room temperature for 30 minutes and then separated from the cells by centrifugation at 3000 rpm for 5 minutes. Serum samples were stored at −80°C until the day of biochemical analysis.
TOS levels were determined using a method previously described by Erel [
TAS levels were determined using a method developed by Erel [
The TOS : TAS ratio was used as OSI. To perform the calculation, the unit of TAS, mmol Trolox equivalent/L, was converted to
Descriptive statistics for the studied variables (characteristics) were presented as Mean ± Standard Deviation. Two-factor experiment with repeated measures on one factor analysis of variance was used to compare the groups and periods for TAS, TOS, and OSI. Following analysis of variance, Tukey’s multiple comparison test was performed to determine different periods. In addition, Student’s
Groups were similar in terms of age, gender, and BSA. The demographic characteristics of the patients are presented in Table
Demographic data of groups.
Whole patients ( |
Group 1 ( |
Group 2 ( |
|
|
---|---|---|---|---|
Age, year | 62.87 ± 10.310 | 63.64 ± 8.582 | 62.17 ± 12.021 | 0.741 |
Male, |
17 (73.9%) | 8 (72.7%) | 9 (75.0%) | 0.901 |
BSA (m2) | 1.838 ± 0.175 | 1.848 ± 0.193 | 1.828 ± 0.165 | 0.793 |
Urea (mg/dL) | 38.13 ± 10.385 | 35.91 ± 13.217 | 40.17 ± 6.887 | 0.338 |
Creatinine (mg/dL) | 0.939 ± 0.282 | 0.918 ± 0.299 | 0.958 ± 0.278 | 0.742 |
ALT (U/L) | 28.57 ± 18.571 | 22.64 ± 10.856 | 34.00 ± 22.700 | 0.147 |
AST (U/L) | 32.96 ± 18.826 | 35.09 ± 22.170 | 31.00 ± 15.915 | 0.614 |
ACE inhibitors, |
11 (47.8%) | 4 (36.4%) | 7 (58.3%) | 0.292 |
Calcium antagonists, |
1 (4.3%) | 0 (0%) | 1 (8.3%) | 0.328 |
Beta blockers, |
4 (17.4%) | 2 (18.2%) | 2 (16.7%) | 0.924 |
Nitrates, |
5 (21.7%) | 2 (18.2%) | 3 (25.0%) | 0.692 |
HT, |
17 (73.9%) | 7 (63.6%) | 10 (83.3%) | 0.283 |
DM, |
5 (21.7%) | 2 (18.2%) | 3 (25.0%) | 0.692 |
COPD, |
3 (13.0%) | 2 (18.2%) | 1 (8.3%) | 0.484 |
PAD, |
2 (8.7%) | 1 (9.1%) | 1 (8.3%) | 0.949 |
CVD, |
1 (4.3%) | 0 (0%) | 1 (8.3%) | 0.328 |
Smoking, |
7 (30.4%) | 2 (18.2%) | 5 (41.7%) | 0.221 |
Alcohol, |
1 (4.5%) | 1 (9.1%) | 0 (0%) | 0.306 |
CCS class | 2.26 ± 0.449 | 2.36 ± 0.505 | 2.17 ± 0.389 | 0.304 |
LVEF | 53.48 ± 9.224 | 52.27 ± 8.475 | 54.58 ± 10.104 | 0.561 |
LMCAD | 1 (4.3%) | 0 (0%) | 1 (8.3%) | 0.328 |
*Comparison of group 1 and group 2.
ACE: angiotensin converting enzyme, ALT: alanine aminotransferase, AST: aspartate aminotransferase, BSA: body surface area, CCS: Canadian Cardiovascular Society, COPD: chronic obstructive pulmonary disease, CVD: cerebrovascular disease, DM: diabetes mellitus, HT: hypertension, LMCAD: left main coronary artery disease, LVEF: left ventricular ejection fraction, and PAD: peripheral arterial disease.
Perioperative variables of groups.
Whole patients ( |
Group 1 ( |
Group 2 ( |
|
|
---|---|---|---|---|
Number of grafts | 2.913 ± 0.996 | 2.636 ± 0.809 | 3.167 ± 1.115 | 0.209 |
LIMA use, |
20 (87%) | 10 (90.9%) | 10 (83.3%) | 0.590 |
ACC time (min) | 44.87 ± 19.212 | 29.18 ± 9.506 | 59.25 ± 13.579 | 0.001 |
CPB time (min) | 98.43 ± 32.481 | 75.64 ± 21.463 | 119.33 ± 26.362 | 0.001 |
Aerobic pump time (min) | 53.57 ± 20.273 | 46.45 ± 20.447 | 60.08 ± 18.574 | 0.109 |
Ventilation time (h) | 8.22 ± 2.864 | 7.86 ± 1.951 | 8.54 ± 3.564 | 0.583 |
ICU stay (h) | 31.87 ± 15.256 | 28.64 ± 15.826 | 34.83 ± 14.758 | 0.342 |
Hospital stay (day) | 5.61 ± 0.783 | 5.64 ± 0.924 | 5.58 ± 0.669 | 0.875 |
*Comparison of group 1 and group 2.
ACC: aortic crossclamp, CPB: cardiopulmonary bypass, h: hours, ICU: intensive care unit, LIMA: left internal mammary artery, and min: minutes.
When all cases of ONCABG were evaluated, the TOS and OSI values of Rp 30 min were significantly higher than the preoperative TOS and OSI values (
In group 2 TOS and OSI values at Rp 30 min were significantly higher than the preoperative values (
TOS, TAS, and OSI values of groups.
Whole patients ( |
Group 1 ( |
Group 2 ( | |
---|---|---|---|
TOS levels ( |
|||
Preoperative | 10.14 ± 7.68 | 9.53 ± 8.08 | 10.69 ± 7.65 |
AC 20 min | 8.81 ± 3.57 | 8.88 ± 4.20 | 8.76 ± 3.23 |
Rp 30 min | 12.47 ± 6.41a | 9.83 ± 3.10 | 15.12 ± 7.82d |
Rp 6 h | 11.72 ± 6.60 | 9.06 ± 3.35 | 14.16 ± 7.96e |
Rp 48 h | 8.79 ± 2.83 | 7.86 ± 1.55 | 10.08 ± 3.73 |
TAS levels (mmol Trolox equivalent/L) | |||
Preoperative | 1.91 ± 0.31 | 1.98 ± 0.37 | 1.86 ± 0.25 |
AC 20 min | 1.83 ± 0.24 | 1.83 ± 0.20 | 1.82 ± 0.29 |
Rp 30 min | 1.79 ± 0.26 | 1.74 ± 0.26c | 1.83 ± 0.27 |
Rp 6 h | 1.92 ± 0.28 | 1.82 ± 0.21 | 2.01 ± 0.31 |
Rp 48 h | 1.87 ± 0.24 | 1.78 ± 0.17 | 1.98 ± 0.28 |
OSI values [( |
|||
Preoperative | 0.54 ± 0.39 | 0.45 ± 0.26 | 0.61 ± 0.49 |
AC 20 min | 0.48 ± 0.17 | 0.49 ± 0.22 | 0.47 ± 0.12f |
Rp 30 min | 0.70 ± 0.36b | 0.57 ± 0.19 | 0.83 ± 0.44g |
Rp 6 h | 0.61 ± 0.32 | 0.50 ± 0.18 | 0.70 ± 0.40 |
Rp 48 h | 0.46 ± 0.13 | 0.44 ± 0.09 | 0.49 ± 0.17 |
aWhen compared to preoperative value
bWhen compared to preoperative value
cWhen compared to preoperative value
dWhen compared to preoperative value
eWhen compared to preoperative value
fWhen compared to preoperative value
gWhen compared to preoperative value
We found that the patients undergoing ONCABG are exposed to potent oxidative imbalance and increase in oxidants at reperfusion which are associated with duration of XC.
CABG procedure induces overproduction of ROS (hydroxyl, hydrogen peroxide, hypochlorite, and superoxide) which originates from various enzymatic and cellular sources [
On the other hand, controversial findings were reported on the perioperative course of antioxidants in CABG patients [
Oxidative stress is an oxidant-antioxidant imbalance status, due to oxidants which exceed the antioxidant capacity. OSI is the ratio of TOS to TAS and is an indicator of OS degree [
In ONCABG patients there are many causes of oxidative stress such as surgical damage, CPB, and ischemia reperfusion injury [
Ischemic period associated with oxidative stress in CABG. Authors reported that XC time was correlated with total peroxide, 8-isoprostane, and nitrites/nitrates levels in patients undergoing CABG [
Ferrari et al. reported a significant and sustained increase in OS in 10 patients undergoing ONCABG with a mean XC duration of 55.2 minutes, while a mild and temporary increase in OS in 10 patients undergoing ONCABG with a mean XC duration of 25.2 minutes [
The oxidative balance change which was more significant at group 2 might be affected from demographic data of patients. The relation between HT and smoking with oxidative balance changes has been reported previously [
The CPB duration of the groups was also different. But there was no difference in terms of aerobic pump times. Prolongation of CPB time in group 2 was mainly due to longer length of XC duration.
Clinical trials conducted with a variety of antioxidant strategies have been largely disappointing. Optimal design of antioxidant strategies in patients undergoing ONCABG needs detailed evaluation of oxidative phenomenon [
The major limitation of the current study may be the relatively small number of patients.
In conclusion, according to assessments of TAS, TOS, and OSI, an oxidative imbalance or increase in OS degree was observed in patients who underwent ONCABG, especially due to an increase in TOS at reperfusion. Moreover, not only increase in TOS at reperfusion but also oxidative imbalance seems to be associated with XC time. These findings inspire further studies which may provide important criteria for antioxidant therapy.
The authors have no personal relationships with other individuals or organizations that might have inappropriately influenced their work during the submission process.
The authors are grateful to Professor Dr. Sıddık Keskin for his assistance in the statistical analysis.