233 Anti-arrhythmic role of sphingosine 1-phospahte in post-operative atrial fibrillation by pak1 activation

Background Atrial Fibrillation (AF) is the most common arrhythmia occurring post cardiac surgery. The incidence varies and depends on the type of surgery. Postoperative AF may cause hemodynamically unstable, that increase the risk of stroke and increase mortality. Current management for prophylaxis of postoperative AF is not satisfactory. Objectives The purpose of this study is to investigate the anti-arrhythmic role of sphingosine 1-phosphate to prevent post-cardiac surgery AF. Methods Sprague-Dawley Rats (300-350grams) Obtained from Harlan Laboratories (Udine, Italy). They were fed standard rat chow, which they had access to ad libitum. Randomly categorised into two groups n=10 each group. One group was treated with sphingosine 1-phospahte receptor agonist fingolimod (1 mg/kg, i.v) and the control group was treated with saline. Following 15 min of treatment, cardioplegic arrest with the support of cardiopulmonary bypass. ECG electrodes were attached to limbs and using power lab charts ECG monitored and analysed. Following monitoring of rhythm for 24 hours, all animals were sacrificed and myocardial tissue was collected to analyse Pak1 protein. Results The administration of fingolimod led to significantly better and fast recovery as compared to the control group. The episodes of AF recorded during 24 hours in the treated group was low versus the control group (p0.001). We also investigated Pak1 protein by western blot and immunohistochemistry. Expression of Pak1 observed higher in the fingolimod-treated group(p0.05). Conclusion Sphingosine 1-phosphate receptor agonist fingolimod plays important role in prevention of AF-related to cardiac surgery by activating the Pak1 pathway.Fingolimod is FDA-approved sphingolipid that can be the potential therapeutic drug for post-operative AF prophylaxis.