Question: 

Right ventricular (RV) pacing results in an impairment of left ventricular (LV) function, which is associated with increased risk of heart failure. In contrast previous studies indicated that LV pacing improves LV performance. In this study we evaluate if pacing leads to cellular remodeling in a chronic animal model and whether there are differential effects between right and left ventricular pacing.

Methods: 

14 minipigs underwent ablation of the atrioventricular node to create a complete AV block, followed by ventricular pacing at 120 beats/min (DDD mode) for one year.7 minipigs were stimulated from the right ventricular free wall (RVFW) and 7 from the left ventricular apex (LVA), respectively. 7 age-matched minipigs were used as controls. LV ejection fraction was determined by echocardiography. High-performance-liquid-chromatography (HPLC) was performed to investigate plasma catecholamines. Furthermore Cx43 expression was analysed by PCR and Western Blot experiments. To obtain histopathological changes after pacing immunhistological staining of fibrotic tissue, hypoxia- induced factor (HIF) and apoptosis- induced factor (AIF) were studied.

Results: 

As a sign of cardiac insufficiency both RVFW and LVA pacing led to increased epinephrine and norepinephrine levels, whereas dopamine levels remained unchanged (LV ejection fraction: control 62±1%, RVFW pacing 28±3%, LVA pacing 45±2%; p=0,0001) . Expression analysis of the gap junction protein Cx43 revealed that RVFW pacing significantly reduced Cx43 mRNA expression in cardiomyocytes of the LV as compared to cardiomyocytes of the LVA- paced group. In the RV there was no difference in Cx43 mRNA expression after pacing. On protein level cardiomyocytes of the RV showed a significant elevated Cx43 protein expression after pacing, regardless of the pacing site. In the LV there was no significant difference in the Cx43 protein expression among the three minipig groups. Furthermore no histological changes of fibrosis, AIF- and HIF- staining occurred after RVFW and LVA pacing compared to control minipigs.

Conclusion: 

RVFW and LVA pacing induce cardiac insufficiency in a chronic minipig model. Furthermore RVFW pacing leads to a reduction in Cx43 mRNA expression in the LV. However ventricular pacing induces no histopathological changes, regardless of the pacing site.