Zusammenfassung
Ischämie und Reperfusionsschaden sind ein wichtiger Faktor für das postoperative Ergebnis in der Herzchirurgie. Es wird daher intensiv nach Möglichkeiten gesucht, diese Art der Schädigung zu reduzieren. In jüngsten Forschungsarbeiten wurden hierbei die protektiven Effekte des NO-cGMP-Protein-Kinase-G-Pathway erforscht. Hierauf basierend untersuchten wir in der aktuellen Forschungsarbeit die Effekte dieses Pathway in einem klinisch relevanten Rattenmodell der Herztransplantation.
Es wurden drei Studien durchgeführt. Die primären Zielparameter waren die kardiale Funktion und die Apoptoserate. Die Pathway-Aktivierung erfolgte durch drei Substrate:
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1.
Vardenafil als Inhibitor der PDE-5 reduzierte den cGMP Abbau,
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2.
Cinaciguat erhöhte durch die Aktivierung der sGC die cGMP-Produktion,
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3.
L-Arginin fungierte als NO-Donor und aktiviert so die sGC.
In allen drei Studien zeigten sich eine signifikante Verbesserung der kardialen Funktion und eine Reduktion der Apoptose. Hieraus folgerten wir, dass eine Aktivierung dieses Pathway die negativen Effekte von Ischämie und Reperfusion reduzieren kann. Eine mögliche Anwendung dieser Substrate in einem klinischen Setting sollte daher geprüft werden.
Abstract
Ischemia and reperfusion are important factors for the outcome after cardiac surgery. Therefore, possibilities are sought to reduce the adverse effects of ischemia/reperfusion injury. Recent scientific research has shown the protective effects of the NO-cGMP-Protein Kinase G (PKG) pathway. In the present work, the effect of this pathway was examined in a clinically relevant model of ischemia/reperfusion injury.
Three studies were performed using the model of heterotopic heart transplantation in rats. The main target parameters were left ventricular function and apoptosis. The NO-cGMP-PKG pathway was targeted by three different agents:
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1.
vardenafil as an inhibitor of PDE-5 reduced the degradation of cGMP,
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2.
cinaciguat as an activator of sGC increased the production of cGMP,
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3.
L-arginine as a NO donor activated sGC.
In each of these experiments, a significant improvement of left ventricular function and a significant reduction of myocardial apoptosis were found. From these results, it can be concluded that targeting the NO-cGMP-PKG pathway can reduce the adverse effects of ischemia/reperfusion injury. Therefore, possible application in a clinical setup should be discussed.
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Loganathan, S., Korkmaz, S., Radovits, T. et al. Die Rolle des NO-cGMP-Protein-Kinase-G-Pathway in der Herzchirurgie. Z Herz- Thorax- Gefäßchir 26, 263–268 (2012). https://doi.org/10.1007/s00398-012-0932-8
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DOI: https://doi.org/10.1007/s00398-012-0932-8