Validation of an animal model of right ventricular dysfunction and right bundle branch block to create close physiology to postoperative tetralogy of Fallot

Thambo, Jean-Benoît; Roubertie, François; Guillebon, Maxime De; Labrousse, Louis; Iriart, Xavier; Ntsinjana, Hopewell; Lafitte, Stéphane; Ploux, Sylvain; Haı̈ssaguerre, Michel; Roques, Xavier; Santos, Pierre Dos; Bordachar, Pierre

doi:10.1016/j.ijcard.2010.08.063

Cited by 11 publications

(24 citation statements)

References 27 publications

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“…In patients with rTOF, QRS duration exceeding 180 ms is considered a predictor of severe ventricular arrhythmias which was linked to RV dilatation 6 11. We have previously identified this QRS feature in our animal model 10 12. In the present study, we found significant conduction disturbances associated with RV-EDVi.…”

Section: Discussionsupporting

confidence: 67%

“…The animal model of rTOF (N=7) was produced as previously described 10. Briefly, piglets (<12 kg) were premedicated with ketamine (10 mg/kg, intramuscular, Vibrac) and acepromazine (0.1 mg/kg, Vetoquinol).…”

Section: Methodsmentioning

confidence: 99%

“…We hypothesised that in patients with rTOF, in addition to scar-based re-entrant circuits, the overloaded RV also undergoes a structural and electrophysiological remodelling that favours re-entries and SCD. We aimed at identifying the underlying mechanisms in a porcine model reproducing TOF postoperative features 10. A better understanding of the electrophysiological and structural substrates late after TOF repair appears essential to identify new risk markers and develop specific antiarrhythmic therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

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Proarrhythmic remodelling of the right ventricle in a porcine model of repaired tetralogy of Fallot

Benoist

Dubes

Roubertie

et al. 2016

Heart

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ObjectiveThe growing adult population with surgically corrected tetralogy of Fallot (TOF) is at risk of arrhythmias and sudden cardiac death. We sought to investigate the contribution of right ventricular (RV) structural and electrophysiological remodelling to arrhythmia generation in a preclinical animal model of repaired TOF (rTOF).Methods and resultsPigs mimicking rTOF underwent cardiac MRI functional characterisation and presented with pulmonary regurgitation, RV hypertrophy, dilatation and dysfunction compared with Sham-operated animals (Sham). Optical mapping of rTOF RV-perfused wedges revealed a significant prolongation of RV activation time with slower conduction velocities and regions of conduction slowing well beyond the surgical scar. A reduced protein expression and lateralisation of Connexin-43 were identified in rTOF RVs. A remodelling of extracellular matrix-related gene expression and an increase in collagen content that correlated with prolonged RV activation time were also found in these animals. RV action potential duration (APD) was prolonged in the epicardial anterior region at early and late repolarisation level, thus contributing to a greater APD heterogeneity and to altered transmural and anteroposterior APD gradients in rTOF RVs. APD remodelling involved changes in Kv4.3 and MiRP1 expression. Spontaneous arrhythmias were more frequent in rTOF wedges and more complex in the anterior than in the posterior RV.ConclusionSignificant remodelling of RV conduction and repolarisation properties was found in pigs with rTOF. This remodelling generates a proarrhythmic substrate likely to facilitate re-entries and to contribute to sudden cardiac death in patients with rTOF.

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Section: Discussionsupporting

confidence: 67%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Proarrhythmic remodelling of the right ventricle in a porcine model of repaired tetralogy of Fallot

Benoist

Dubes

Roubertie

et al. 2016

Heart

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“…Other groups have used the pig for studying PR [18][19][20]. Our porcine model was the first pure model, free of scar tissue, which was examined with morphometric methods and electrophysiology.…”

Section: Discussionmentioning

confidence: 99%

Myocardial hypertrophy after pulmonary regurgitation and valve implantation in pigs

Smith

Goetze

Søndergaard

et al. 2012

International Journal of Cardiology

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“…Such a physiology is usually reproduced in large animals by plication of the pulmonary valve leaflets combined with pulmonary trunk banding. 54 Secondary tricuspid regurgitation occurs so that RV volume overload is progressive. Impairment of RV systolic function and LV compliance are observed after 3 months.…”

Section: Pulmonary Regurgitation Modelsmentioning

confidence: 99%

Experimental Models of Right Heart Failure: A Window for Translational Research in Pulmonary Hypertension

Guihaire

Bogaard

Flécher

et al. 2013

Semin Respir Crit Care Med

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The right ventricle (RV) faces major changes in loading conditions associated with cardiovascular and pulmonary vascular disorders. Despite major pharmacological advances since the last decade, pulmonary arterial hypertension remains a deadly disease mainly secondary to the development of right ventricular failure (RVF). Several experimental models of RVF have been developed over the past three decades providing a particular insight in RV pathophysiology. Mechanisms involved in the transition from RV adaptive hypertrophy to maladaptive remodeling and failure in conditions of chronic RV pressure or volume overload are of a great interest but not yet completely understood. Further investigations are needed to find new therapeutic approaches for RVF. Current animal models and emerging concepts of translational RV research will be detailed in this review.

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Validation of an animal model of right ventricular dysfunction and right bundle branch block to create close physiology to postoperative tetralogy of Fallot

Cited by 11 publications

References 27 publications

Proarrhythmic remodelling of the right ventricle in a porcine model of repaired tetralogy of Fallot

Proarrhythmic remodelling of the right ventricle in a porcine model of repaired tetralogy of Fallot

Myocardial hypertrophy after pulmonary regurgitation and valve implantation in pigs

Experimental Models of Right Heart Failure: A Window for Translational Research in Pulmonary Hypertension

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