Atrial ganglionated plexus Stimulation Prevents Myocardial Ischemia Reperfusion Arrhythmias by Preserving Connexin43 Protein Background: Vagal nerve stimulation has been shown to provide protective effect against ischemia/reperfusion (I/R) arrhythmias. Since atrial epicardial ganglionated plexuses contain a large amount of parasympathetic elements, we hypothesize atrial epicardial ganglionated plexus stimulation (GP-S) may be an alternative to vagal nerve stimulation for preventing arrhythmias induced by myocardial I/R. Methods and Results: Twenty one dogs were randomly divided into GP stimulation (GP-S) group (N=11) and control group (N=10). Myocardial I/R was induced by first 2 hours of reperfusion in dogs subjected to 45 minutes of ischemia with occlusion of the left anterior descending coronary artery (LAD). A bipolar plaque electrode was sutured overlying the fad pad containing the superior left ganglionated plexus (SLGP), which located at the junction of left pulmonary artery and left superior pulmonary vein.The GP-S was performed by applying high frequency electrical stimulation (HFS: 20Hz, 0.1msec duration) to the SLGP. The lowest voltage level of GP-S that induced approximately 10% sinus rhythm slowing was chosen as the voltage for GP-S. Compared with control group, GP-S caused significant increases in ventricular ERP and vagal indice (HF nu), as well as an evident decrease in sympathetic tone (LF/HF), the numbers of PVCs, salvos, and VT runs were significantly reduced in GP-S group. And the incidences of salvo and VT in GP-S group were significantly lower. Immunoblotting revealed that the control group showed a marked reduction in the amount of phosphorylated connexin43 (Cx43), whereas the GP-S group showed only a slight reduction. Immunohistochemistry confirmed that the myocardial I/R-induced loss of Cx43 from intercellular junctions was prevented by GP-S. Conclusions: GP-S protects against ventricular arrhythmias resulting from brief myocardial I/R by modulating connexin43. GP-S may serve as a non-pharmacological clinical approach to improve acute myocardial I/R arrhythmias such as during coronary bypass surgery.