Molecular and Cellular Biochemistry

, Volume 379, Issue 1–2, pp 43–49 | Cite as

Pharmacological postconditioning by bolus injection of phosphodiesterase-5 inhibitors vardenafil and sildenafil

  • Bernd Ebner
  • Annette Ebner
  • Anna Reetz
  • Stefanie Böhme
  • Antje Schauer
  • Ruth H. Strasser
  • Christof Weinbrenner


Postconditioning enables cardioprotection against ischemia/reperfusion injury either by application of short, repetitive ischemic periods or by pharmacological intervention prior to reperfusion. Pharmacological postconditioning has been described for phosphodiesterase-5 inhibitors when the substances were applied as a permanent infusion. For clinical purposes, application of a bolus is more convenient. In a rat heart in situ model of ischemia reperfusion vardenafil or sildenafil were applied as a bolus prior to reperfusion. Cardioprotective effects were found over a broad dosage range. In accordance with current hypotheses on pharmacological postconditioning signaling, the protective effect was mediated by extracellular signal-regulated kinase and protein kinase C pathway. Interestingly, the extent of protection was independent of the concentration applied for both substances. Full protection comparable to ischemic postconditioning was reached with half-maximal human equivalence dose. In contrast, mean arterial pressure dropped upon bolus application in a dose-dependent manner. Taken together, the current study extends previous findings obtained in a permanent infusion model to bolus application. This is an important step toward clinical application of pharmacological postconditioning with sildenafil and vardenafil, especially because the beneficial effects were proven for concentrations with reduced hemodynamic side effects compared to the dosage applied for erectile dysfunction treatment.


Postconditioning PDE5 Bolus application Ischemia Myocardial infarction Cardioprotection 



Analysis of variance


Protein kinase B


Body weight


Cyclic guanosine monophosphate


Enzyme-linked immunosorbent assay


Extracellular-regulated kinase


Glycogen synthase kinase 3β


High performance liquid chromatography


ATP-dependent potassium channels


Mean arterial pressure


Mitochondrial permeability transition pore


Phosphodiesterase 5


Protein kinase C


Protein kinase G


Reperfusion injury salvage kinase


Ramus interventricularis anterior


Standard error of mean




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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Bernd Ebner
    • 1
  • Annette Ebner
    • 1
  • Anna Reetz
    • 1
  • Stefanie Böhme
    • 1
  • Antje Schauer
    • 1
  • Ruth H. Strasser
    • 1
  • Christof Weinbrenner
    • 1
    • 2
  1. 1.Department of Medicine/Cardiology, Heart Center DresdenUniversity Hospital, University of Technology DresdenDresdenGermany
  2. 2.Medizinische Klinik IKlinikum HanauHanauGermany

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