Cardiac development in relation to clinical supraventricular arrhythmias : focus on structure-function relations

Supraventricular 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.UBL - phd migration 201

Avanços recentes em nutrição de larvas de peixes

Os requisitos nutricionais de larvas de peixes são ainda mal compreendidos, o que leva a altas mortalidades e problemas de qualidade no seu cultivo. Este trabalho pretende fazer uma revisão de novas metodologias de investigação, tais como estudos com marcadores, genómica populacional, programação nutricional, génomica e proteómica funcionais, e fornecer ainda alguns exemplos das utilizações presentes e perspectivas futuras em estudos de nutrição de larvas de peixes

Accessory Atrioventricular Myocardial Pathways in Mouse Heart Development: Substrate for Supraventricular Tachycardias

Cardiac Dysfunction and Arrhythmia

Electrical Activation of Sinus Venosus Myocardium and Expression Patterns of RhoA and Isl-1 in the Chick Embryo

Methods and Results: Expression of RhoA, myocardial markers cTnI and Nkx2.5, transcription factors Isl-1 and Tbx18, and cation channel HCN4 were examined in sequential stages in chick embryos. Electrical activation patterns were studied using microelectrodes and optical mapping. Embryonic sinus venosus myocardium is cTnI and HCN4 positive, Nkx2.5 negative, complemented by distinct patterns of Isl-1 and Tbx18. During development, initial myocardium-wide expression of RhoA becomes restricted to right-sided sinus venosus myocardium, comprising the SAN. Electrophysiological measurements revealed initial capacity of both atria to show electrical activity that in time shifts to a right-sided dominance, coinciding with persistence of RhoA, Tbx18, and HCN4 and absence of Nkx2.5 expression in the definitive SAN. Conclusion: Results show an initially bilateral electrical potential of sinus venosus myocardium evolving into a right-sided activation pattern during development, and suggest a role for RhoA in conduction system development. We hypothesize an initial sinus venosus-wide capacity to generate pacemaker signals, becoming confined to the definitive SAN. Lack of differentiation toward a chamber phenotype would explain ectopic pacemaker foci. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1284-1292, November 2010).Stem cells & developmental biolog