Dokument: Effekte des If-Kanal-Inhibitors Ivabradin auf humanes atriales Myokard im Vergleich zum β-Blocker Metoprolol
| Titel: | Effekte des If-Kanal-Inhibitors Ivabradin auf humanes atriales Myokard im Vergleich zum β-Blocker Metoprolol | |||||||
| Weiterer Titel: | Effects of the If-channel inhibitor Ivabradine on human atrial myocardium in comparison to β-blocker Metoprolol | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=15992 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20100913-074429-7 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Dr. Leder, Marc-Christian [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Schipke, Jochen D. [Betreuer/Doktorvater] Prof. Dr. Gödecke, Axel [Gutachter] | |||||||
| Stichwörter: | Herzfrequenz Heart rate force Inotropie Inotropy run down ioa | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Der Zusammenhang zwischen einer erhöhten Herzfrequenz (HF) und kardialer Morbiditäten und Mortalität ist belegt. Durch die Entwicklung der If-Inhibitoren ergibt sich eine Möglichkeit, zur direkten Einflußnahme auf die HF. Mit Ivabradin (Iva) ist seit 2005 der erste Vertreter dieser Substanzklasse auf dem deutschen Markt. Ivabradin zeigte keinen Einfluß auf Inotropie oder andere kardiale Parameter außer der Chronotropie. Es traten nur wenige, gut tolerierbare Nebenwirkungen auf. β-Blocker haben seit langem ihre Bedeutung in der Behandlung myokardialer Ischämien und Arrhythmien unter Beweis gestellt. Sie reduzieren Morbidität und Mortalität.
Diese Arbeit ging der Frage nach, ob Iva negativ inotrope Effekte auf atriales Myokard und Kontraktionsmuster hat. Dafür wurde atriales Gewebe aus kardiochirurgischen Eingriffen (Durchführung mittels Extrakorporaler Zirkulation; 44 Patienten) benutzt und Iva mit dem β-Blocker Metoprolol (Met) verglichen. Mittels einer Placebo-Reihe, wurde der natürliche 'run-down' ermittelt und die Ergebnisse für Iva und Met damit korrigiert. Als Parameter für die Inotropie wurde die systolische (Fmax), die disatolische Kraft (Fmin) und die Amplitude beider (Fdev) gemessen. Parameter für die systolische Kontraktionszeit war die Time-to-Peak-Force (TPF), für die frühe diastolische Realaxationszeit die Time-to-half-Relaxation (THR). In therapeutischen Konzentrationen zeigte Iva keine, Met sehr wohl negativ inotrope Effekte. Met zeigte keinen Einfluß auf die systolische Kontraktionsphase, während Iva diese verlängerte. Met verkürzte die frühe diastolische Relaxationsphase, während diese durch Iva unbeeinflußt blieb. Damit wird nun erstmals gezeigt, daß Ivabradin auf das Vorhofmyokard ebenfalls keinen negativ inotropen Effekt hat. Dies ist insofern von klinischer Bedeutung, da der Vorhof ca. 10 % zur diastolischen Ventrikelfüllung beiträgt.The relationship between an increased heart rate (HR), cardiac morbidity and mortality is verified. The development of If-inhibitors allows a direct influence on the HF. Ivabradine (Iva) is the first representative of the If inhibitors in Germany. Ivabradine showed no effects on inotropy or other cardiac parameters except for the chronotropy. There were only a few, well-tolerable side effects. β-blockers demonstrated their importance in the treatment of myocardial ischemia and arrhythmias. They reduced morbidity and mortality. This study examined if Iva has negative inotropic effects on atrial myocardium and contraction parameters. Atrial tissue from cardiac surgery (by extracorporeal circulation; 44 patients) was used and Iva was compared to the β-blocker metoprolol (Met). By using a placebo-series the natural 'run-down' was determined corrected according to the results for Iva and Met. The systolic force (Fmax), the diastolic force (Fmin) and the amplitude of both (f dev) were measured as parameters for inotropy. The parameter for systolic contraction time was the time-to-peak force (TPF) and for the early diastolic realaxation time the time-to-half relaxation (THR). At therapeutic concentrations Iva showed no, Met indeed negative inotropic effects. Met had no effect on the systolic contraction phase whereas Iva extended the systolic contraction phase. Met significantly reduced the early diastolic relaxation phase while it was unaffected by Iva. For the first time, this study demonstrates that ivabradine has no negative inotropic effect as well as on the atrial myocardium. This is a matter of vital importance since the atrial contribution to diastolic ventricular filling is about 10%. | |||||||
| Quelle: | Herold G et al.
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| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 13.09.2010 | |||||||
| Dateien geändert am: | 08.09.2010 | |||||||
| Promotionsantrag am: | 31.05.2009 | |||||||
| Datum der Promotion: | 13.07.2010 |
