The heart is a syncytium: electrical impulses propagate freely between cells in every direction, so that the myocardium functions as a single contractile unit. This property allows rapid, synchronous depolarization of the myocardium. While normally advantageous, this property can be detrimental as it potentially allows the propagation of incorrect electrical signals during cardiac arrhythmias. Impulse propagation in the heart is dependent upon the substrate (i.e. cardiac tissue itself) and the autonomic nervous system. The ‘substrate’ composes three major determinants for electrical impulse propagation: 1. Electrical excitability of the cardiac cells (myocytes) determined by the voltage-gated sodium channels (encoded by the SCN5A gene). 2. Electrical coupling between the myocytes, mediated by intercellular gap junction channels (Connexin 43 gap junctions in the ventricles) 3. Tissue architecture, i.e. cell size, extracellular collagen matrix and under pathologic conditions, increased fibrosis. During pathologic conditions, such as heart failure, myocardial infarction, Brugada syndrome, or arrhythmogenic right ventricular dysplasia, one or more of these factors may be modified, cause slow impulse propagation and increase the vulnerability of the heart to arrhythmias. The research described in this thesis has concentrated on these three factors and their influence on impulse propagation and arrhythmias. From the results described in this thesis we concluded that the heart has a ‘conduction reserve’; the heart is able to maintain near normal levels of impulse conduction when a single determinant of impulse conduction is altered. An interesting observation was that the right ventricle has a lower conduction reserve than the left ventricle, as conduction in the right ventricle is more readily affected by alterations in conduction parameters. In conclusion, this thesis sheds light on the effect that alterations in determinants of impulse propagation have on conduction, and on conduction reserve that protects the heart from impaired conduction if conduction parameters are only moderately altered
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