Proefschrift--Utrecht. / Summary in Dutch. Bibliography: p. 101-108.

Proefschrift--Utrecht. / Summary in Dutch. Bibliography: p. 101-108.

Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2007. / Includes bibliographical references (leaves 118-129). Also available in electronic version.

Thesis (Ph. D.)--Duke University, 2008.

Stretch of cardiac muscle is known to activate various physiological processes that result in changes to cardiac function, contractility and electrophysiology. To date, however, the precise relationship between mechanical stretch and changes in the electrophysiology of the heart remain unclear. This relationship, termed mechanoelectric feedback (MEF), is thought to underlie many cardiac arrhythmias associated with pathological conditions. These electrophysiological changes are observed not only in the whole heart, but also at the single cardiomyocyte level, and can be explained by the presence of stretch-activated ion channels (SACs). Most investigations of the actions of stretch have concentrated on these sacrolemmal ionic currents thought responsible for the proposed MEF-induced changes in contractility. While these studies have provided some useful insight into possible mechanisms, the inappropriate use of solutions and non-physiological degrees of stretch, may have caused somewhat misleading results. Currently, little is known about the involvement or contribution of non-selective or K+ selective SACs to the normal cardiac cycle. Here, I investigate the concept that stretch-induced changes in cardiac electrophysiology (MEF) are important in normal cardiac cycle and demonstrate the effects of stretch on the Frank-Starling mechanism (stretch induced increases in cardiac contractility) while pharmacologically manipulating stretch-activated ion currents. Experiments were conducted using a number of agents known to influence stretch-activated channels either in a positive or antagonistic manner. Results proved somewhat negative toward MEF theory with only substantial or pathological levels of stretch being able to elicit any electrophysiological change in the heart. Furthermore, where electrophysiological changes were associated with pathological stretch they were not consistently modulated by stretch-activated ion channel activators or blockers. Of equal importance was the observation that smaller levels of myocardial stretch associated with positive changes in contractility via the Frank-Starling mechanism were not associated with any electrophysiological changes in the Langendorff perfused heart (as observed by monophasic action potentials) nor in isolated muscle preparations (as observed through transcellular membrane potential recordings). As such, the present research undertaken in this thesis confirms an absence of electrophysiological changes with stretch except under extreme conditions suggesting that MEF is not a robust and necessarily repeatable phenomenon in the mammalian heart. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1320476 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008

Role of Nkx2.5 on development and electrophysiology of the mouse heart Prague 2015 Bc. Peter Hámor ABSTRACT The objective of this thesis is to investigate the role of Nkx2.5 gene dosage on electrophysiology of the mouse heart in prenatal stage of its development, in which the physiological functions of the heart fail to function properly. The main goal of this work is to search for differences in conduction of electric impulses through the embryonic mouse heart according to their genotype. Special method of capturing the conduction of electric impulse through myocardium was used for this purpose, called optical mapping. Thanks to this method I was able to construct images and videos capturing transition of the impulse with marked beginning of the activation and its direction in the heart. These outputs, or optical maps, help to define anomalies and defects compared with a normal functioning heart. The thesis focuses on the expression of the transcription factor Nkx2.5 and regulatory components related with the correct formation and physiology of the heart until 9.5 days post coitum. Individuals in this developmental stage were optically mapped and compared according to their genotypes - homozygous non-mutant, heterozygote and homozygous mutant mouse embryos exhibited some degree of similarity, while other...

Role of Nkx2.5 in development and electrophysiology of the mouse heart Prague 2016 Peter Hámor, B.S. ABSTRACT The objective of this thesis is to investigate the role of Nkx2.5 gene dosage on electrophysiology of the mouse heart in prenatal stage of its development. The main goal of this work is to search for differences in conduction of electric impulses through the embryonic mouse hearts of different genotype. Special method of capturing the conduction of electric impulse through myocardium, called optical mapping, was used to visualize the electrical activity. Thanks to this method I was able to construct images and videos capturing the spread of the impulse with identification of the beginning of the activation and its direction in the heart. These outputs, or optical maps, help to define anomalies and defects in mutants compared with a normal functioning heart. The thesis focuses on the expression of the transcription factor Nkx2.5 and regulatory components related with the correct formation and physiology of the heart until 9.5 days post coitum. Embryos at this developmental stage were optically mapped and analysed according to their genotype. While the wild type and heterozygote mouse embryos exhibited high degree of similarity, the homozygous mutants were dramatically different. Considering this work...