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Right or left ventricular pacing in young minipigs with chronic atrioventricular block: long-term in vivo cardiac performance, morphology, electrophysiology, and cellular biology
A Salameh, S Dhein, K Blanke, A Rastan, B Hiyasat, A Dietze, A Sobiraij, I Dahnert, J Janousek
Language English Country United States
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- MeSH
- Atrioventricular Block diagnostic imaging physiopathology therapy MeSH
- Chronic Disease MeSH
- Ventricular Dysfunction, Left diagnostic imaging physiopathology therapy MeSH
- Ventricular Dysfunction, Right diagnostic imaging physiopathology therapy MeSH
- Echocardiography MeSH
- Electrophysiological Phenomena MeSH
- Hemodynamics physiology MeSH
- Cardiac Pacing, Artificial * MeSH
- Connexin 43 metabolism MeSH
- Patch-Clamp Techniques MeSH
- Swine, Miniature MeSH
- Disease Models, Animal MeSH
- Myocardium cytology metabolism MeSH
- Swine MeSH
- Heart physiology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
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.
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