Electrophysiologic and anatomical relationships studied in primum atrioventricular septal defect

Hakacova, Nina

doi:10.1016/j.jelectrocard.2009.09.005

Cited by 2 publications

(3 citation statements)

References 29 publications

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“…In DS patients, such AV block and P wave changes have been recorded [6], [17] and related to the AV node displacement in AVSD [11]. Changes in the electrical axis, duration of the QRS and fragmented QRS, observed in Ts65Dn hearts are all characteristics of abnormal ventricular activation that have been described in Hsa21 trisomy [6], [17]–[19] and more generally in CHD [27]–[29]. S wave amplitude, specifically large in mouse and most likely due to specific His-Purkinje bundle and strands/fasciculae distributions [22], contributes largely to the QRS axis changes.…”

Section: Discussionmentioning

confidence: 83%

“…S wave amplitude, specifically large in mouse and most likely due to specific His-Purkinje bundle and strands/fasciculae distributions [22], contributes largely to the QRS axis changes. In DS and CHD, different QRS axis orientations are related to either primum or secundum ASD, VSD or AVSD [28], [29] and changes in the activation front. An altered organization of the AV node axis [11], [28] and a conduction defect in the trabecular myocardium and papillary muscles sustaining the valves involving the His-Purkinje system [29] could account for such changes.…”

Section: Discussionmentioning

confidence: 99%

“…In DS and CHD, different QRS axis orientations are related to either primum or secundum ASD, VSD or AVSD [28], [29] and changes in the activation front. An altered organization of the AV node axis [11], [28] and a conduction defect in the trabecular myocardium and papillary muscles sustaining the valves involving the His-Purkinje system [29] could account for such changes. Fragmented QRS (f-QRS) are predictive of arrhythmias [30], [31], a common complication of DS and CHD [5], [11], [12].…”

Section: Discussionmentioning

confidence: 99%

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The App-Runx1 Region Is Critical for Birth Defects and Electrocardiographic Dysfunctions Observed in a Down Syndrome Mouse Model

et al. 2012

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Down syndrome (DS) leads to complex phenotypes and is the main genetic cause of birth defects and heart diseases. The Ts65Dn DS mouse model is trisomic for the distal part of mouse chromosome 16 and displays similar features with post-natal lethality and cardiovascular defects. In order to better understand these defects, we defined electrocardiogram (ECG) with a precordial set-up, and we found conduction defects and modifications in wave shape, amplitudes, and durations in Ts65Dn mice. By using a genetic approach consisting of crossing Ts65Dn mice with Ms5Yah mice monosomic for the App-Runx1 genetic interval, we showed that the Ts65Dn viability and ECG were improved by this reduction of gene copy number. Whole-genome expression studies confirmed gene dosage effect in Ts65Dn, Ms5Yah, and Ts65Dn/Ms5Yah hearts and showed an overall perturbation of pathways connected to post-natal lethality (Coq7, Dyrk1a, F5, Gabpa, Hmgn1, Pde10a, Morc3, Slc5a3, and Vwf) and heart function (Tfb1m, Adam19, Slc8a1/Ncx1, and Rcan1). In addition cardiac connexins (Cx40, Cx43) and sodium channel sub-units (Scn5a, Scn1b, Scn10a) were found down-regulated in Ts65Dn atria with additional down-regulation of Cx40 in Ts65Dn ventricles and were likely contributing to conduction defects. All these data pinpoint new cardiac phenotypes in the Ts65Dn, mimicking aspects of human DS features and pathways altered in the mouse model. In addition they highlight the role of the App-Runx1 interval, including Sod1 and Tiam1, in the induction of post-natal lethality and of the cardiac conduction defects in Ts65Dn. These results might lead to new therapeutic strategies to improve the care of DS people.

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