ATRIAL FIBRILATION AND GAMA GLUTAMYL TRANSFERASE ; OF-PUMP VERSUS ON-PUMP CORONARY ARTERY BYPASS SURGERY

Introduction: Atrial fibrillation (AF) which can be seen as a complication of the open heart surgery, may  cause serious problems on post operative period. The exact pathophysiology of AF is unknown but it is thought that factors such as oxidative stress might cause AF. Material and methods : We retrospectivily surveyed the serum gamma glutamyl transferase (GGT) levels which is accepted as a mediator of oxidative stres, for the Post Operative Atrial Fibrillation (POAF) that occur after of-pump versus on-pump Coronary Artery Bypass Graft (CABG) surgery. Our study included 183 cases ( 101 male, 72 female; median age 63 ± 4.3 years) of which CABG was performed. Results: Echocardiography, routine blood tests, electrocardiography (ECG), test for the serum GGT levels were performed in preoperative and postoperative  period to all participants. AF developed  in 34 patients (35 %) in Group I and 19 patients (20 %) in Group II. There were no significant differences between two groups (of-pump versus on-pump) in terms of gender, cardiovascular risk factors and the severity of the coronary artery disease. In patients who has developed AF in postoperative period had significantly higher serum GGT levels. Conclusion : This study has shown that serum GGT levels were found to be significantly higher in patients whom AF has developed after on-pump CABG surgery.


INTRODUCTION
Atrial fibrillation (AF) is the most common pathologic arrhythmia among clinical arrhythmias and can be seen in coronary artery disease, hypertension, mitral valve diseases and hyperthyroidism. AF can also be seen idiopathically. Recently, in addition to these risk factors, obesity, metabolic syndrome, chronic alcoholism and atherosclerosis have been reported as other etiological factors of AF (1). Oxidative stress is thought to be an important physiopathological mechanism in the developement of POAF since antioxidant agents such as ascorbic acid is found to be important in the prevention of the developement of POAF (2,3). Serum gamma glutamyl transferase (GGT) enzyme is important in the homeostasis of the glutathione which is responsible for the protection of the cells from the free oxygen radicals. GGT is related with hepatobiliary diseases and alcohol consumption. There are studies in which the use of the serum concentrations of GGT as a marker for increased oxidative stress (4). It has also been postulated that increased serum GGT levels and cardiovascular diseases and the metabolic syndrome are closely related (5,6). Because of these facts we investigated the relationship of serum GGT which is a marker for increased oxidative stress with POAF.

MATERIALS AND METHODS
Our study included 183 cases of which CABG was performed in Gaziantep Dr. Ersin Arslan Education and Research Hospital between 2012 and 2017. Patients who had chronic liver disease, preoperative AF, wide left atrium (> 5 cm) and patients who had indications for emergency CABG were excluded from this study. Echocardiography, routine blood tests, electrocardiography (ECG), test for the serum GGT levels were performed in preoperative and postoerative period to all participants.

Biochemical analysis
A venous blood specimen (5 mL) was collected at 6:00 a.m. to 7:00 a.m. Serum was separated by centri- Original article fugation at 1500 × g for 15 min. All laboratory analysis were performed at the department of central bio chemistry labarotry. Serum GGT levels were measured spectrophotometrically with the Beckman DXC800 automatic biochemical analyzer (USA). Reference range for GGT was 7-49 U/L.

Surgical Technic
Off-pump and On-pump CABG procedures were performed through a median sternotomy approach. Octopus and Starfish (Medtronic, USA) was used to stabilize the target coronary vessel in all off-pump CABG cases . Revascularization in on-pump CABG was performed by standard surgical technique with moderate systemic hyperthermia (30-32°c). Conduits for both off-pump and on-pump CABG included the internal mammary artery or saphenous veins, or a combination of the two. All patients were continuously monitored in the intensive care unit (ICU) postoperatively. A 12-lead ECG recording was performed to confirm the AF episodes. POAF was defined as the characteristic arrhythmia lasting for more than 5 minutes. POAF was treated by amiodarone and replacement of potassium and magnesium. Patients were periodically examined in our outpatient clinics especially who had POAF. All continuous variables were presented as mean ± SD. Student t-test was used for analysis of continuous variables and Chi-squared test was used.

RESULTS
183 cases were divided into two groups; Group I included the patients (n: 96) who had on-pump CABG,

DISCUSSION
POAF is the mostly encountered arrythmic complication of CABG which is estimated to 5-30 % (7A).
If AF is untreated it is one of the leading cause of postoperative morbidity and mortality (7). It usually is seen on 2nd or 3th postoperative day (8). There are many studies of-pump CABG lowers the incidence of PO-AF(9,10), but also there are authors on the contrary (11,12). In our study POAF is seen with significantly higher incidence in on-pump CABG compared to of-pump CABG. This is the main postulate of this study. There are multifactorial mechanisms are questioned for POAF. It could be of either slow atrial conduction nature or dispersion of atrial refractoriness (13). Especially Archobold stated that; a combination of prolonged signal-averaged P-wave duration (SAPD), advanced age, and male sex identifies patients at high risk for development of POAF (13). AF is accepted to be reentrant in origin, so sustained AF requires that the depolarizing wave fronts continuously encounter excitable tissue, a circumstance favored by slow atrial conduction and a short atrial refractory period (14). It has been found that atrial myositic calcium load and electrophysiological remodelling of the atrial tissue is fo-   (15). Plasma peroxidase levels were found to be increased after aortic cross clamping, in patients whom CABG operation was performed (7,16). POAF can develop in an environment in which there is increased oxidative but there isn't enough anti oxidants present. Violi reports on experimental and clinical studies exploring the role of Reactive oxygen species (ROS) in eliciting the occurrence or recurrence of AF and the potential efficacy of a treatment by antioxidant vitamins (17). Stanger states that Ischemia-reperfusion has been reported to be associated with augmented oxidative stress in the course of surgery, which might be causally involved in the onset of atrial fibrillation (AF), the most common arrhythmia after cardiac surgery. So he hypothesized that supplementation of antioxidants and n-3 polyunsaturated fatty acids (n-3 PUFAs) might lower the incidence of AF following coronary artery bypass graft (CABG) surgery. And finally he concludes that the administration of vitamins attenuates post-operative oxidative stress in the course of CABG surgery (18). GGT is the enzyme for the seperation of gamma gluthamyl from glutathione which itself is an important antioxidant. Because of the close relationship between serum GGT levels and inflammation and atherosclerosis (8) the developement of POAF which occurs in a similar fashion is found to be significantly related with the serum GGT levels as well. GGT as an enzyme that is derived from the liver is postulated to have an independent relationship between postoperative AF (19). The mean age is found to be significantly higher in Group I in which postoperative AF occured (p < 0.05) and thus the age group in this study is considered to be appropriate. Postoperative AF is found to be more often in the second and third postoperative days and serum GGT levels are found to be increased in the first postoperative day. This might affect the statistyical analiysis but since history of MI was among the exclusion criteria elevated levels of serum GGT may be an independent risk factor for AF.

CONCLUSION
The leading etiological factors for the developement of postoperative AF are inflammation and oxidative stress. Thus it is imperative to perform the tests for imflammatory markers and the markers of oxidative stress in the preoperative period in order to develop preventive treatment protocols for such complications of CABG operation.