Effect of Remote Ischemic Preconditioning on Incidence of Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass Graft Surgery A Randomized Controlled Trial

Atrial fibrillation is the most common arrhythmic complication after coronary artery bypass grafting (CABG) (1). It remains challenging to prevent, treat, or cure (2). It contributes to increased mortality (3), heart failure (4), stroke (5), increase in length of hospital stay, intensive care unit readmission, and treatment costs (6). The pathogenesis of atrial fibrillation (AF) after cardiac surgery is considered to be multifactorial. Some of the factors include patient's preoperative status, age, and preexisting electrocardiogram abnormalities (7). Intra-operative stress also plays key role due to occurrence of reperfusion, inflammation, oxidative stress, or hemostasis (8, 9). Post operatively, almost all AF episodes occur within the first 6 days following cardiac surgery, with the peak incidence on the second or third post-operative day which coincides with the peak of systemic inflammation caused by surgery and with atrial stretch (10).

Despite improvement in medical therapy, surgical technique, and anesthesia AF occurs in 25-40% of patients undergoing CABG (1, 11). However a recent meta-analysis demonstrated that pharmacological therapy that reduces post-operative AF, reduces length of stay, the cost of the hospitalization, and potential stroke (12). Therefore, there has been great interest to establish strategies to prevent this arrhythmia. Ischemic preconditioning is among the strategies which have shown myocardial protective effect during CABG (13). It was first described in 1986 in dog to provide a protective effect on the myocardium that is later subjected to a sustained bout of ischemia (14). Subsequently, in various clinical setting it demonstrated that ischemic preconditioning reduces the incidence of cardiac arrhythmias (15). In addition the efficacy of preconditioning in cardiac surgery and percutaneous coronary interventions has been demonstrated in human being (16).

The exact cellular mechanism of preconditioning is still controversial. Among mediators such as NO˙, ˙OH, and ONOO- which may play role in both ischemia/reperfusion injury and in the development of the cardio-protective effects of preconditioning (17); NO˙ has been considered to attenuate oxidative stress mediated cell injury during ischemia/ reperfusion. However, whether NO˙ plays a protective or detrimental role in myocardial ischemia/reperfusion injury or preconditioning remains controversial (18, 19). In a recent study, Jannati et al. demonstrated that myocardial ischemic preconditioning by aortic cross clamping in patients undergoing CABG reduced the incidence of post operative AF (20).

Currently there is no clinical preconditioning protocol or tool being utilized during CABG. Additionally, aortic cross clamping may increase the risk of embolic stroke, particularly in elderly patients (21). Therefore, we are conducting a prospective single-blinded randomized controlled study to demonstrate whether remote ischemic preconditioning reduces incidence of post operative AF.

IV. RESEARCH DESIGN