Abstract 362: Cardioprotective Effects of Adiponectin in Volume Overload Induced Electrophysiological Remodeling

Abstract

The electrophysiological hallmark of the failing heart is the prolongation of action potential duration that induces arrhythmia and sudden death. Depressed outward potassium currents (Ito) has been implicated as the major cause of altered action potential during ventricular remodeling. The molecular mechanism underlying depressed Ito in the diseased heart is still poorly understood. Recent studies have demonstrated that adiponectin (APN) has a cardio-protective effect in response to various pathological stimuli; however, little information is available regarding the potential effects of APN on electrophysiological remodeling under pathological conditions. The present study were to determine the effect of adiponectin treatment on ventricular potassium channel function in a rat model of volume overload induced heart failure. Volume-overload was induced by surgical creation of an infrarenal aorta-vena cava fistula. Rats were administrated with or without adenovirus-mediated overexpression of adiponectin (Ad-APN) at 2-, 5- and 8- weeks post-fistula. In vivo ECGs were used to evaluate changes in QT interval in rats at 10 weeks post-fistula. Ventricular myocytes were isolated at 10 weeks post-fistula. Western blots were used to measure cytoplasmic and membrane protein expression of potassium channels Kv4.2 and Kv 4.3, as well as, KChIP2. Whole cell patch clamp was used to evaluate action potential and Ito currents. Results showed that adiponectin levels in serum and myocytes were significantly reduced following fistula. The duration of action potential was prolonged in ventricular myocytes following 10-week fistula, which was correlated with the in vivo QT interval prolongation, as well as a depression of functional Ito and decreased protein expression of Ito channel subunits in ventricular myocytes. In vivo supplementation of Ad-APN increased the protein levels of Ito channel subunits and prevented Ito depression in ventricular myocytes following 10-week fistula. This further restored the duration of action potential and the QT interval on the ECG back to the normal. These results indicate that adiponectin was able to prevent volume overload-induced ventricular electrophysiological remodeling.