Spatial heterogeneity of protein expression induced by dyssynchronous right ventricular pacing in the left ventricle of dogs with preserved systolic function

Background: Right ventricular (RV) apical pacing may result in ventricular dyssynchrony, which is associated with functional and morphological changes in the left ventricle (LV). Our aim is to assess contraction and hypertrophy-related protein expression changes in the LV after RV apical pacing. Methods and Results: Six dogs underwent dual chamber pacemaker (DDD) implantation and atrioventricular nodal catheter ablation. The pacing group received atria-sensed RV apical pacing for 12 weeks. LV dyssynchrony was assessed with speckle tracking technique. Subsequently, hearts were processed for Western blotting. Four sham-operated dogs were included for comparison. After 12 weeks of RV pacing, cardiac chamber size and LV ejection fraction remained unchanged. Both electrical and mechanical dyssynchrony were evident in RV-paced dogs compared with sham-operated dogs. The late-activated LV lateral wall of paced dogs displayed a 23% reduction in the amount of sarcoplasmic reticulum Ca²⁺ ATPase, a 32% reduction in phospholamban levels, but a 3.6-fold increase in phospho-JNK expression, a 2.2-fold increase in phospho-p38, and 1.9-fold increase in phospho-ERK expression. There were no significant differences in the early-activated LV septum between paced and sham dogs. Conclusions: Temporal dispersion of mechanical activation by RV apical pacing induced spatial dispersion of protein expression in the LV.