Abstract
High doses of proton pump inhibitors like pantoprazole (PP) are used in treatment of acid-related gastrointestinal diseases. Here, we investigated the effects of pantoprazole on cardiac function.
Trabeculae were dissected from right auricle of patients undergoing cardiac surgery, from explanted ventricles of patients undergoing heart transplantation and from hearts of healthy adult rabbits. Trabeculae were superfused with different concentration of pantoprazole-containing buffer at physiological conditions (Krebs-Henseleit-buffer, 37 °C, pH 7.35, 1,25 mM Ca2+). Rabbit trabeculae were used to measure intracellular pH using BCECF. Isolated ventricular myocytes from rabbits were used to investigate effect of pantoprazole on calcium-homeostasis and SR calcium uptake using Fura-2 and Fluo-3 as fluorescence indicators. Calcium-sensitivity was estimated using skinned fibres from adult rabbit hearts.
In presence of pantoprazole a dose-dependent decrease of developed force was observed in trabeculae dissected from ventricles with terminal heart failure. The EC50 of this effect was 17.3 ± 1.3 μg/mL. Similar results were observed in trabeculae from human atria as well as in rabbit ventricles. In isolated rabbit myocytes, reduced amplitude of the intracellular calcium transient was found (40 μg/mL pantoprazole; by −25 ± 8 % compared with control). The amplitude of the L-type Ca2+ current (ICa,L) was decreased by 35 ± 5 % and SR Ca2+-content was reduced by 18 ± 6 %. An oxalate-supported cuvette assay of SR-Ca2+ uptake revealed a lower Ca2+-sensitivity (Kd) of the SR Ca2+ ATPase (control Kd = 358 ± 15 nM; 40 μg/mL pantoprazole, Kd = 395 ± 12 nM (p < 0.05). Additionally, pantoprazole caused a reduced Ca2+-activated force of cardiac myofilaments. Effects on intracellular pH by pantoprazole were not found.
These data demonstrate a reduced cardiac contractile function in-vitro induced by pantoprazole. These effects are due to reduced calcium homeostasis and myofilament activity.
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© 2007 Springer Medizin Verlag Heidelberg
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Teucher, N. et al. (2007). Mechanismus des negativ-inotropen Effektes des Protoneninhibitors Pantoprazol in Mensch und Kaninchen. In: Steinau, H.U., Schackert, H.K., Bauer, H. (eds) Chirurgisches Forum 2007. Deutsche Gesellschaft für Chirurgie, vol 36. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-71123-0_133
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DOI: https://doi.org/10.1007/978-3-540-71123-0_133
Publisher Name: Springer, Berlin, Heidelberg
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