Arrhythmogenic Remodeling of the Left Ventricle in a Porcine Model of Repaired Tetralogy of Fallot

Dubes, Virginie; Benoist, David; Roubertie, François; Gilbert, Stephen; Constantin, Marion; Charron, Sabine; Elbes, Delphine; Vieillot, Delphine; Quesson, Bruno; Cochet, Hubert; Haı̈ssaguerre, Michel; Rooryck, Caroline; Bordachar, Pierre; Thambo, Jean-Benoît; Bernus, Olivier

doi:10.1161/circep.117.006059

Cited by 13 publications

(13 citation statements)

References 32 publications

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“…Here we show that AP duration and morphology are comparable in slices from transmural core biopsies and tissue blocks from the same pig ventricular regions. Median APD values (117 ms and 111 ms in the biopsy and block slices, respectively) are slightly lower than previously published values in experimental works on multicellular preparations [40][41][42][43][44] , which could be explained by the fact that our pig samples come from www.nature.com/scientificreports/ piglets and young pigs. Indeed, in our APD measures we could observe a trend to shorter APD in those from piglets as compared to those from adult pigs.…”

Section: Discussioncontrasting

confidence: 69%

Minimally invasive system to reliably characterize ventricular electrophysiology from living donors

Oliván-Viguera

Pérez-Zabalza

García-Mendívil

et al. 2020

Sci Rep

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Cardiac tissue slices preserve the heterogeneous structure and multicellularity of the myocardium and allow its functional characterization. However, access to human ventricular samples is scarce. We aim to demonstrate that slices from small transmural core biopsies collected from living donors during routine cardiac surgery preserve structural and functional properties of larger myocardial specimens, allowing accurate electrophysiological characterization. In pigs, we compared left ventricular transmural core biopsies with transmural tissue blocks from the same ventricular region. In humans, we analyzed transmural biopsies and papillary muscles from living donors. All tissues were vibratome-sliced. By histological analysis of the transmural biopsies, we showed that tissue architecture and cellular organization were preserved. Enzymatic and vital staining methods verified viability. Optically mapped transmembrane potentials confirmed that action potential duration and morphology were similar in pig biopsies and tissue blocks. Action potential morphology and duration in human biopsies and papillary muscles agreed with published ranges. In both pigs and humans, responses to increasing pacing frequencies and β-adrenergic stimulation were similar in transmural biopsies and larger tissues. We show that it is possible to successfully collect and characterize tissue slices from human myocardial biopsies routinely extracted from living donors, whose behavior mimics that of larger myocardial preparations both structurally and electrophysiologically.

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Section: Discussioncontrasting

confidence: 69%

Minimally invasive system to reliably characterize ventricular electrophysiology from living donors

Oliván-Viguera

Pérez-Zabalza

García-Mendívil

et al. 2020

Sci Rep

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“…Similar findings were found in the LV, despite preserved LV function at this stage. This demonstrates biventricular adverse effects are present early in the adverse remodeling process 127 .…”

Section: Knowledge Gapsmentioning

confidence: 86%

Current outcomes and treatment of tetralogy of Fallot

et al. 2019

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Tetralogy of Fallot (ToF) is the most common type of cyanotic congenital heart disease. Since the first surgical repair in 1954, treatment has continuously improved. The treatment strategies currently used in the treatment of ToF result in excellent long-term survival (30 year survival ranges from 68.5% to 90.5%). However, residual problems such as right ventricular outflow tract obstruction, pulmonary regurgitation, and (ventricular) arrhythmia are common and often require re-interventions. Right ventricular dysfunction can be seen following longstanding pulmonary regurgitation and/or stenosis. Performing pulmonary valve replacement or relief of pulmonary stenosis before irreversible right ventricular dysfunction occurs is important, but determining the optimal timing of pulmonary valve replacement is challenging for several reasons. The biological mechanisms underlying dysfunction of the right ventricle as seen in longstanding pulmonary regurgitation are poorly understood. Different methods of assessing the right ventricle are used to predict impending dysfunction. The atrioventricular, ventriculo-arterial and interventricular interactions of the right ventricle play an important role in right ventricle performance, but are not fully elucidated. In this review we present a brief overview of the history of ToF, describe the treatment strategies currently used, and outline the long-term survival, residual lesions, and re-interventions following repair. We discuss important remaining challenges and present the current state of the art regarding these challenges.

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“…In a porcine model of repaired TOF, the remodeling of RV conduction and the repolarization properties are associated with a decreased Cx43 protein expression, as well as enhanced lateralization of the protein [60]. A trend towards increased Cx43 lateralization after repaired TOF is also observed in the piglet LV [61]. In addition, a reduced amount of the Cx43 mRNA occurs one year after TOF repair in dogs, although the Cx40 mRNA level is not altered [62].…”

Section: Tetralogy Of Fallotmentioning

confidence: 84%

Importance of Cx43 for Right Ventricular Function

Boengler

Rohrbach

Weißmann

et al. 2021

IJMS

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In the heart, connexins form gap junctions, hemichannels, and are also present within mitochondria, with connexin 43 (Cx43) being the most prominent connexin in the ventricles. Whereas the role of Cx43 is well established for the healthy and diseased left ventricle, less is known about the importance of Cx43 for the development of right ventricular (RV) dysfunction. The present article focusses on the importance of Cx43 for the developing heart. Furthermore, we discuss the expression and localization of Cx43 in the diseased RV, i.e., in the tetralogy of Fallot and in pulmonary hypertension, in which the RV is affected, and RV hypertrophy and failure occur. We will also introduce other Cx molecules that are expressed in RV and surrounding tissues and have been reported to be involved in RV pathophysiology. Finally, we highlight therapeutic strategies aiming to improve RV function in pulmonary hypertension that are associated with alterations of Cx43 expression and function.

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Arrhythmogenic Remodeling of the Left Ventricle in a Porcine Model of Repaired Tetralogy of Fallot

Abstract: Supplemental Digital Content is available in the text.

Cited by 13 publications

References 32 publications

Minimally invasive system to reliably characterize ventricular electrophysiology from living donors

Minimally invasive system to reliably characterize ventricular electrophysiology from living donors

Current outcomes and treatment of tetralogy of Fallot

Importance of Cx43 for Right Ventricular Function

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