Die vorliegende Studie zeigt erstmals, dass eine erhöhte Ca2+-Empfindlichkeit der kardialen Myofilamente im Tiermodell einen selbstständigen Risikofaktor bei der Entstehung von Herzrhythmusstörungen darstellt. Dies konnte sowohl für chronische Erhöhung der Ca2+-Empfindlichkeit im Rahmen einer Familiären Hypertrophen Kardiomyopathie (FHK) als auch für eine akute Erhöhung mit Hilfe eines Ca2+-Sensitizers gezeigt werden. Die Ergebnisse der Arbeit bieten so eine mögliche Erklärung für plötzlichen Herztod bei bestimmten Patienten mit FHK. Sie schränken weiterhin den Einsatz von Ca2+-Sensitizern ein. Schließlich beleuchten sie einen bisher kaum untersuchten Aspekt in der Arrhythmogenese von Herzinsuffizienz und nach einem Myokard-Infarkt. Auf zellulärer Ebene findet sich ein veränderter Ca2+-Zyklus mit erniedrigten und verlangsamten Transienten. Diese Veränderungen sind wahrscheinlich eine direkte Konsequenz der erhöhten Bindungsaffinität für Ca2+. Die Myofilamente sind „klebriger“ für Ca2+, während der Systole wird mehr Ca2+ gebunden, während der Diastole hingegen dissoziiert es langsamer. Bei adrenerger Stimulation und schnellen Herzfrequenzen mit entsprechender Verkürzung der Diastole kommt es zu erhöhtem diastolischem [Ca2+]i und zu erhöhten Ca2+-Inhalt des Sarkoplasmatischen Retikulums. Der so veränderte Ca2+-Zyklus führt wahrscheinlich mit Hilfe des Na+/Ca2+-Austauschers zu Veränderungen der Repolarisation des Aktionspotentials. Bei schnellen Herzfrequenzen treten Aktionspotential-Verlängerung, Ca2+-abhängige Nachdepolarisationen und getriggerte Schläge auf. Auf Organ-Ebene findet sich eine verkürzte Refraktärzeit. Damit sind sowohl ein Trigger als auch ein arrhythmogenes Substrat für die beobachteten ventrikulären Arrhythmien gegeben. / The present study shows for the first time that increased Ca2+-sensitity of the cardiac myofilaments is an indepent mechanism in the development of cardiac arrhythmias. This could be shown both for chronically increased Ca2+-sensitity in Familial Hypertrophic Cardiomyopathy (FHC) and for acute drug-induced Ca2+-sensitization. The results provide an explanation for sudden cardiac death in certain patients with FHC. Moreover they limit the use of Ca2+-sensitizers. Furthermore they elucidate new aspects in the arrhythmogenesis of important aquired hearts diseases such as heart failure and myocardial infarction. On the cellular level the Ca2+-cycle is altered, Ca2+-transients show a smaller amplitude and slower rate of decay. These changes are probably a direct consequence of the increased Ca2+-puffering capacity. The myofilaments are “sticky” for Ca2+, durig systole more Ca2+ is bound while the dissociation during diastole is decelerated. With adrenergic stimulation and faster frequencies there is an increased diastolic [Ca2+]i and subsequently an Ca2+-overloading of the Sarcoplasmatic Reticulum. These changes in the Ca2+-cycle cause remodelling of the action potential repolarisation via the Na+-Ca2+-exchanger. At fast frequencies one finds action potential prolongation, Ca2+-dependent afterdepolarisations and triggered activity. On the organ level Ca+-sensitized hearts show a shortened refractory period. Thus there is both trigger and substrate for the observed ventricular arrhytrhmia.

In this mini-dissertation the writer analyzed Hubert du Plessis’ Drie Stukke vir Fluit en Klavier, opus 25. He researched why Du Plessis uses three shorter series of different lengths. The relationship between the series in this work was researched, as well as the characteristic applications of the series. It was found that Du Plessis uses shorter series of different lengths as his compositional tool, because they are manageable and can be manipulated for any specific requirement or need. With fewer notes in a series, if chromatic notes are avoided, the music will lean itself to an impression of tonality. It is interesting for the researcher how the feeling of tonality was portrayed through the use of different series and hence the given dissertation was researched. In true atonal music, composers usually disregard third and halftone intervals. Yet, tritones are often used in atonal music. In retrospect, Du Plessis uses more third and halftone intervals than tritones. There is only one tritone in this work (found in the second series), as opposed to the use of third and halftone intervals throughout all three series. The feeling of tonality is further enhanced through fragments of the series that one can place in a specific key. With this in mind, it is evident to get the impression of tonality as a result of fragmentation from the series. Another aspect of tonality that cannot be ignored was the composer’s use of bitonality. The serial techniques that Du Plessis used, was also researched. It was found that Du Plessis did not make use of any new innovations. All these techniques were already used by composers like Schoenberg, Berg, Webern and Dallapiccola. The most important techniques that Du Plessis used, were: <ul> <li>The use of all the forms of the series and their transpositions</li> <li>Overlapping series (that is when the last note of the series, becomes the first note of the next series)</li> <li>Combination of series (superimposition)</li> <li>The dividing of series between the instruments</li> <li>The repetition of notes in a series before all the notes have been used</li> <Li>Sometimes notes are put in a different order, thereby losing the correct order of the series.</li></ul> / Dissertation (MMus)--University of Pretoria, 2008. / Music / unrestricted