Sheep can be used as animal model of regional myocardial remodeling and controllable work

Background: Pacing the right heart has been shown to induce reversible conduction delay and subsequent 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 ventricular 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 remodeled 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.