This thesis is separated in two parts (Part I and Part II) in which normal and abnormal heart development are studied and related to congenital heart disease, in particular to the etiology of... Show moreThis thesis is separated in two parts (Part I and Part II) in which normal and abnormal heart development are studied and related to congenital heart disease, in particular to the etiology of supraventricular arrhythmias in fetuses and neonates. Part I describes the development of the posterior heart field derived venous pole of the heart specifically in correlation to the role of Shox2 and podoplanin in that particular area. Furthermore, the developmental processes in this region seem to have an important role in the anlage of the cardiac conduction system and epicardial lineage development of the heart. In the second part of this thesis (Part II) the aetiology of a specific subtype of supraventricular tachycardias i.e. atrioventricular reentry tachycardias (AVRTs) are related to normal heart development in human and mouse. AVRTs are one of the most common types of tachyarrhythmias at the perinatal period of development. We demonstrate that perinatal AVRTs might be related to incomplete formation of the isolating annulus fibrosus resulting in the temporary persistence of accessory myocardial connections between the atria and ventricles. We furthermore, demonstrate the late outcome of fetal brady- and tachyarrhythmia cases. Show less
Askar, S.F.A.; Ramkisoensing, A.A.; Schalij, M.J.; Bingen, B.O.; Swildens, J.; Laarse, A. van der; ... ; Pijnappels, D.A. 2011
In this thesis we describe normal and abnormal pulmonary vein development in human and mouse hearts, and focus on the histo(patho)logy of the pulmonary venous and left atrial dorsal wall, in order... Show moreIn this thesis we describe normal and abnormal pulmonary vein development in human and mouse hearts, and focus on the histo(patho)logy of the pulmonary venous and left atrial dorsal wall, in order to elucidate the role of the posterior heart field in the formation and differentiation of the pulmonary venous vessel wall and its possible consequences for the onset of arrhythmias and susceptibility for pulmonary vein stenosis. Another aim of this thesis is that the understanding of normal pulmonary vein development will contribute to the understanding of the development of abnormal pulmonary venous connections and its clinical consequences. Show less
Hoogendijk, M.G.; Potse, M.; Linnenbank, A.C.; Verkerk, A.O.; Ruijter, H.M. den; Amersfoorth, S.C.M. van; ... ; Coronel, R. 2010
Supraventricular tachycardias (SVTs) are amongst the most commonly encountered cardiac arrhythmias in clinical practice in both children and adults. The causative mechanisms underlying the... Show moreSupraventricular tachycardias (SVTs) are amongst the most commonly encountered cardiac arrhythmias in clinical practice in both children and adults. The causative mechanisms underlying the appearance of most of these SVTs have however still remained as intriguing as they are unexplained. In this thesis, cardiac development is analyzed in relation to the etiology of clinical supraventricular arrhythmias with a special focus on structure-function relations. Firstly, in PART I of this thesis, both the (patho) physiological development of the annulus fibrosus cordis and the etiological origin of clinical accessory AV pathway (AP) mediated AVRT in children and adults is analyzed in experimental animal models and human sections. Secondly, in PART II of this thesis a review of the different ontogenic theories on the embryonic development of the AV Node (AVN) in literature is followed by an experimental study postulating a new concept on the developmental origin of the AVN in relation to the etiology of AV Nodal Reentrant Tachycardia (AVNRT). As a general introduction to both these basic research (I & II) and the clinical (III) parts of this thesis, structural cardiac development in avians (with references to equivalent mouse and human developmental timelines) (Figure 1) will first be described since the development of the cardiac conduction system (CCS) and structural cardiogenesis are intimately related. Next, the developmental transitions in impulse propagation and the construction of the individual components of the specialized CCS and the AVN in particular will be shortly outlined. Following a description of the changes in electrocardiograms (ECGs) during cardiogenesis, current concepts on the transitions in ventricular activation sequences during embryogenesis will be discussed. Thereafter, contemporary knowledge on the development of the isolating annulus fibrosis, the key structure involved in AP persistence, in relation to general CCS development will be reviewed. Subsequently, relevant genera l characteristics of the different animal models and the immunohistochemical markers used in this thesis are briefly discussed. Following the description of the structural basics of cardiogenesis, attention will be focused on current knowledge of clinical SVTs in neonates and children and the treatment of these arrhythmias. These therapeutic clinical issues will be further outlined in PART III of this thesis. Show less
