Abstract 4123: Regional Protein Expression Changes in the Left Ventricle After Chronic Atrial-synchronized Right Ventricular Pacing in Dogs: Molecular Effect of Ventricular Dyssynchrony

Introduction: Right ventricular (RV) pacing with relevant ventricular dyssynchrony may predispose to the incidence of heart failure hospitalization in patients of sinus node dysfunction and AV block. However, the detrimental effect of contraction dyssynchrony on left ventricle (LV) in molecular level has never been investigated. Whether contraction dyssynchrony would alter stress and function-related protein expression in various stretched parts of LV was studied in a canine model of atrial-synchronized RV pacing.Methods: Totally 10 dogs receiving dual-chamber (DDD) pacemakers were included. 6 dogs underwent AV nodal catheter ablation and then programmed to VDD mode, while 4 dogs were sham group without pacing. After 3 months of obligatory atrial-synchronized RV pacing, we analyzed the stress and function related proteins expression in different portions of the LV in addition to echocardiographic evaluation of cardiac function.Results: In the obligatory RV pacing hearts, lateral endocardium of the LV demonstrated 45% reduction in sarcoplasmic reticulum Ca2+ ATPase, 32% reduction in phospholamban, 5.7 folds increase in phospho-JNK expression, but no changes in phospho-p38 and phospho-ERK expression, compared to sham group (Table⇓). However, no significant changes of protein expression in LV lateral mid/epicardium, LV septum and RV septum between the two groups.Conclusions: Ventricular dyssynchrony caused by artificial RV pacing adversely up regulated stress protein and down regulated functional protein expression in the late-activated LV lateral endocardium. These findings support the detrimental scenario of artificial RV pacing in molecular level.