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
Article

Abstract

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.

Keywords

Postconditioning PDE5 Bolus application Ischemia Myocardial infarction Cardioprotection 

Abbreviations

ANOVA

Analysis of variance

Akt

Protein kinase B

BW

Body weight

cGMP

Cyclic guanosine monophosphate

ELISA

Enzyme-linked immunosorbent assay

ERK

Extracellular-regulated kinase

GSK-3β

Glycogen synthase kinase 3β

HPLC

High performance liquid chromatography

KATP

ATP-dependent potassium channels

MAP

Mean arterial pressure

mPTP

Mitochondrial permeability transition pore

PDE5

Phosphodiesterase 5

PKC

Protein kinase C

PKG

Protein kinase G

RISK

Reperfusion injury salvage kinase

RIVA

Ramus interventricularis anterior

SEM

Standard error of mean

TBAS

Tetrabutylammoniumhydrogensulfate

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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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