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

Cardiol J. 2019;26(4):375-384. doi: 10.5603/CJ.a2018.0007. Epub 2018 Mar 23.

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.

Keywords: animal model; dyssynchrony; pacing; regional myocardial work; remodeling.

MeSH terms

  • Action Potentials
  • Animals
  • Bundle-Branch Block / diagnosis
  • Bundle-Branch Block / etiology
  • Bundle-Branch Block / physiopathology*
  • Cardiac Pacing, Artificial*
  • Disease Models, Animal
  • Disease Progression
  • Heart Conduction System / physiopathology*
  • Heart Rate*
  • Hypertrophy, Left Ventricular / diagnostic imaging
  • Hypertrophy, Left Ventricular / etiology
  • Hypertrophy, Left Ventricular / physiopathology*
  • Male
  • Mitral Valve Insufficiency / etiology
  • Mitral Valve Insufficiency / physiopathology
  • Sheep, Domestic
  • Stroke Volume
  • Time Factors
  • Ventricular Dysfunction, Left / diagnostic imaging
  • Ventricular Dysfunction, Left / etiology
  • Ventricular Dysfunction, Left / physiopathology*
  • Ventricular Function, Left*
  • Ventricular Pressure
  • Ventricular Remodeling*