Right or left ventricular pacing in young minipigs with chronic atrioventricular block: Long-term in vivo cardiac performance, morphology, electrophysiology, and cellular biology

摘要

Background-Left ventricular (LV) dyssynchrony may occur as a result of right ventricular (RV) pacing and is a known risk factor for the development of heart failure. In children with complete atrioventricular block, pacing-induced dyssynchrony lasting for decades might be especially deleterious for LV function. To determine the hemodynamic and ultrastructural remodeling after either RV free wall or LV apical pacing, we used a chronic minipig model. Methods and Results-Fourteen piglets 8 weeks of age underwent atrioventricular node ablation and were paced from either the RV free wall or the LV apex at 120 bpm for 1 year (7 age-matched minipigs served as controls with spontaneous heart rates of 104±5 bpm). Echocardiographic examinations, pressure-volume loops, patch-clamp investigations, and examinations of connexin43, calcium-handling proteins, and histomorphology were carried out. RV free wall-paced minipigs exhibited significantly more LV dyssynchrony than LV apex-paced animals, which was accompanied by worsening of LV function (maximum LV mechanical delay/LV ejection fraction: RV free wall pacing, 154±36 ms/28±3%, LV apical pacing, 52±19 ms/45±2%, control 47±14 ms/62±1%; P=0.0001). At the cellular level, both pacemaker groups exhibited a significant reduction in L-type calcium and peak sodium current, shortening of action potential duration and amplitude, increased cell capacity, and alterations in the calcium-handling proteins that were similar for RV free wall-and LV apex-paced animals. Conclusions-The observed molecular remodeling seemed to be more dependent on heart rate than on dyssynchrony. LV apical pacing is associated with less dyssynchrony, a more physiological LV contraction pattern, and preserved LV function as opposed to RV free wall pacing.