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

Jürgen Duchenne, Piet Claus, Efstathios D. Pagourelias, Razvan O. Mada, Joeri Van Puyvelde, Kathleen Vunckx, Eric Verbeken, Olivier Gheysens, Filip Rega, Jens-Uwe Voigt
DOI: 10.5603/CJ.a2018.0007
·
Pubmed: 29570208

open access

Ahead of print
Original articles
Published online: 2018-01-25

Abstract

Background: A-V-sequential pacing has been shown to induce reversible conduction delay and subsequent asymmetric remodelling of the left ventricle (LV) in dogs and pigs. Both species have disadvantages in animal experiments.  Therefore aim of this study focusses at developing a more feasible and easy-to-use animal model in sheep.

Methods: Dual-chamber pacing (DDD) pacemakers (right atrium + right ventricular free wall) were surgically 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 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 remodelling (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 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: Herein is developed a new sheep model with an asymmetrically remodelled LV. Simple pacemaker programming allows  direct modulation of regional myocardial function and work. This 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 remodelling.

Abstract

Background: A-V-sequential pacing has been shown to induce reversible conduction delay and subsequent asymmetric remodelling of the left ventricle (LV) in dogs and pigs. Both species have disadvantages in animal experiments.  Therefore aim of this study focusses at developing a more feasible and easy-to-use animal model in sheep.

Methods: Dual-chamber pacing (DDD) pacemakers (right atrium + right ventricular free wall) were surgically 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 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 remodelling (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 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: Herein is developed a new sheep model with an asymmetrically remodelled LV. Simple pacemaker programming allows  direct modulation of regional myocardial function and work. This 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 remodelling.

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Keywords

animal model, regional myocardial work, pacing, dyssynchrony, remodeling

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Title

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

Journal

Cardiology Journal

Issue

Ahead of print

Published online

2018-01-25

DOI

10.5603/CJ.a2018.0007

Pubmed

29570208

Keywords

animal model
regional myocardial work
pacing
dyssynchrony
remodeling

Authors

Jürgen Duchenne
Piet Claus
Efstathios D. Pagourelias
Razvan O. Mada
Joeri Van Puyvelde
Kathleen Vunckx
Eric Verbeken
Olivier Gheysens
Filip Rega
Jens-Uwe Voigt

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