Jürgen Duchenne1, Piet Claus2, Efstathios D Pagourelias2, Razvan O Mada2, Joeri Van Puyvelde3, Kathleen Vunckx4, Eric Verbeken5, Olivier Gheysens4, Filip Rega3, Jens-Uwe Voigt2. 1. Department of Cardiovascular Sciences and Department of Cardiovascular Diseases, KU Leuven - University of Leuven and University Hospitals Leuven, Leuven, Belgium. jurgen.duchenne@outlook.com. 2. Department of Cardiovascular Sciences and Department of Cardiovascular Diseases, KU Leuven - University of Leuven and University Hospitals Leuven, Leuven, Belgium. 3. Department of Cardiovascular Sciences and Department of Cardiothoracic Surgery, KU Leuven - University of Leuven and University Hospitals Leuven, Leuven, Belgium. 4. Department of Imaging and Pathology and Department of Nuclear Medicine, KU Leuven - University of Leuven and University Hospitals Leuven, Leuven, Belgium. 5. Department of Imaging and Pathology and Department of Pathology, KU Leuven - University of Leuven and University Hospitals Leuven, Leuven, Belgium.
Abstract
BACKGROUND: Pacing the right heart has been shown to induce reversible conduction delay and subse-quent asymmetric remodeling of the left ventricle (LV) in dogs and pigs. Both species have disadvantages in animal experiments. Therefore the aim of this study was to develop a more feasible and easy-to-use animal model in sheep. METHODS: Dual-chamber (DDD) pacemakers with epicardial leads on the right atrium and right ven-tricular free wall were implanted in 13 sheep. All animals underwent 8 weeks of chronic rapid pacing at 180 bpm. Reported observations were made at 110 bpm. RESULTS: DDD pacing acutely induced a left bundle branch block (LBBB) - like pattern with almost doubling in QRS width and the appearance of a septal flash, indicating mechanical dyssynchrony. Atrial pacing (AAI) resulted in normal ventricular conduction and function. During 8 weeks of rapid DDD pacing, animals developed LV remodeling (confirmed with histology) with septal wall thinning (-30%, p < 0.05), lateral wall thickening (+22%, p < 0.05), LV volume increase (+32%, p < 0.05), decrease of LV ejection fraction (-31%, p < 0.05), and functional mitral regurgitation. After 8 weeks, segmental pressure-strain-loops, representing regional myocardial work, were recorded. Switching from AAI to DDD pacing decreased immediately work in the septum and increased it in the lateral wall (-69 and +41%, respectively, p < 0.05). Global LV stroke work and dP/dtmax decreased (-27% and -25%, respectively, p < 0.05). CONCLUSIONS: This study presents the development a new sheep model with an asymmetrically remod-eled LV. Simple pacemaker programing allows direct modulation of regional myocardial function and work. This animal model provides a new and valuable alternative for canine or porcine models and has the potential to become instrumental for investigating regional function and loading conditions on regional LV remodeling.
BACKGROUND: Pacing the right heart has been shown to induce reversible conduction delay and subse-quent asymmetric remodeling of the left ventricle (LV) in dogs and pigs. Both species have disadvantages in animal experiments. Therefore the aim of this study was to develop a more feasible and easy-to-use animal model in sheep. METHODS: Dual-chamber (DDD) pacemakers with epicardial leads on the right atrium and right ven-tricular free wall were implanted in 13 sheep. All animals underwent 8 weeks of chronic rapid pacing at 180 bpm. Reported observations were made at 110 bpm. RESULTS:DDD pacing acutely induced a left bundle branch block (LBBB) - like pattern with almost doubling in QRS width and the appearance of a septal flash, indicating mechanical dyssynchrony. Atrial pacing (AAI) resulted in normal ventricular conduction and function. During 8 weeks of rapid DDD pacing, animals developed LV remodeling (confirmed with histology) with septal wall thinning (-30%, p < 0.05), lateral wall thickening (+22%, p < 0.05), LV volume increase (+32%, p < 0.05), decrease of LV ejection fraction (-31%, p < 0.05), and functional mitral regurgitation. After 8 weeks, segmental pressure-strain-loops, representing regional myocardial work, were recorded. Switching from AAI to DDD pacing decreased immediately work in the septum and increased it in the lateral wall (-69 and +41%, respectively, p < 0.05). Global LV stroke work and dP/dtmax decreased (-27% and -25%, respectively, p < 0.05). CONCLUSIONS: This study presents the development a new sheep model with an asymmetrically remod-eled LV. Simple pacemaker programing allows direct modulation of regional myocardial function and work. This animal model provides a new and valuable alternative for canine or porcine models and has the potential to become instrumental for investigating regional function and loading conditions on regional LV remodeling.
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