Atrial Fibrillation Substrate in Heart Failure: Expression Levels of Cardiac Sodium Channel, Connexin 43 and Connexin 40 in the Left Atrium

Introduction: Reduction in cardiac sodium current and gap junctional proteins (connexin43 and 40) may play important role in reduction of conduction velocity of the propagating wave and providing substrate for Atrial Fibrillation (AF). We sought to determine the changes in the protein levels of SCNA5, Cx43 and Cx40 in the left atrial tissue in a dog model of heart failure.Method: In five dogs, rapid right ventricular pacing was performed at 240bpm for three weeks to induce heart failure. Then AF inducibility was assessed by rapid atrial pacing. In five control dogs, AF inducibility was assessed similarly, followed by removal of the atria. The levels of SCNA5, Cx43, and Cx40 were detected in the Posterior Left Atrium (PLA) and Left Atrial Appendage (LAA) tissues of the CHF and control dogs using western blot technique.Results: All animals with heart failure showed sustained inducible AF (i.e. >5 minutes) in the electrophysiology study. No AF was induced in the control dogs (p<0.05). Cardiac SCNA5 protein levels were decreased in both PLA and LAA tissues compared to the control (56% and 37%, P < 0.05). Cx43 and Cx40 levels were significantly decreased only in LAA tissues of the heart failure animals compared to the control (12% and 53%, P<0.05). The changes in Cx43 and Cx40 levels in PLA tissue of heart failure dogs were not statistically significant.Conclusion: Decreased level of SCNA5 protein which may result in decreased sodium current can provide substrate for AF in heart failure. In addition, significantly decreased levels of gap junctional proteins (CX43 and 40) in LAA provide additional substrate for impaired conduction and arrhythmia as well as impairing contractility and predisposing to thrombus formation in LAA.