Zusammenfassung
Ziel
Analyse des Kontraktionsverhaltens und des intrazellulären Kalziumstoffwechsels im isolierten atrialen Myokard des Menschen.
Methoden
Isoliertes menschliches atriales Myokard aus chirurgischem Resektionsmaterial wurde mit Fura 2 zur Messung des intrazellulären Kalziums untersucht. Die Präparate wurden supramaximal elektrisch stimuliert. Kraftentwicklung und intrazelluläres Kalzium wurden bei ansteigenden Ivabradin-Konzentrationen simultan gemessen. Unterschiedliche Stimulationsfrequenzen wurden verwendet, um die Kraft-Frequenz-Beziehung unter Ivabradin-Einfluss zu analysieren.
Ergebnisse
Mit steigender Ivabradin-Konzentration kam es zu einem signifikanten Anstieg der Amplituden des intrazelluären Kalziumtransienten und der Kraftamplituden (p<0,01) und zu einer Reduktion des intrazellulären diastolischen Kalziums (p<0,01). Ein signifikanter Anstieg der Kraft wurde bei 5 µM Ivabradin beobachtet. Eine Erhöhung der Dosis führte zu keinem weiteren Anstieg des positiv inotropen Effektes.
Schlussfolgerung
Die Daten belegen für Ivabradin einen positiv inotropen Effekt und jenseits des Sinusknotens nachweisbare Effekte auf das Kontraktionsverhalten des atrialen menschlichen Myokards.
Abstract
Objectives
The present study tests, whether Ivabradine has an action aside from the sinus node in human atrial tissue.
Methods
Human atrial myocardium was loaded with the fluorescent dye Fura 2 for intracellular calcium measurements. The preparations were electrically stimulated at optimal length while diastolic and systolic intracellular calcium and mechanical force output were simultaneously recorded. Increasing Ivabradine concentrations were tested. Varying stimulation frequencies were applied in order to analyse the force frequency relation under conditions of Ivabradine incubation.
Results
Increasing Ivabadrin concentrations had a direct effect in increasing the amplitude of intracellular calcium transient and on the amplitude of active force generation (p<0.01). There was a reduction of diastolic intracellular calcium and of diastolic resting force with increasing Ivabradine concentrations (p<0.01). Increases of the Ivabradine dose did not further increase the positive inotropic effect.
Conclusion
Ivabradine has a positive inotropic effect aside from the sinus node in atrial myocardium. It is a substance with a direct positive inotropic effect as shown by the present data.
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Karliova, I., Denk, K., Hakami, L. et al. Positiv inotroper Effekt von Ivabradin am atrialen Myokard des Menschen. Z Herz- Thorax- Gefäßchir 23, 204–211 (2009). https://doi.org/10.1007/s00398-009-0730-0
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DOI: https://doi.org/10.1007/s00398-009-0730-0