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Article Open Access

Analysis of conditioning with dexmedetomidine under endothelial dysfunction in isolated perfused hearts

  • Authors:
    • Sophia De Luca-rohner
    • André Heinen
    • Martin Stroethoff
    • Annika Raupach
  • View Affiliations / Copyright

    Affiliations: Department of Anaesthesiology, Medical Faculty and University Hospital Düsseldorf, Heinrich‑Heine‑University Düsseldorf, Düsseldorf D-40225, Germany, Institute for Cardiovascular Physiology, Medical Faculty and University Hospital Düsseldorf, Heinrich‑Heine University Düsseldorf, Düsseldorf D-40225, Germany
    Copyright: © De Luca-rohner et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 136
    |
    Published online on: June 11, 2025
       https://doi.org/10.3892/br.2025.2014
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Abstract

Cardioprotective strategies such as pharmacological conditioning have not yet successfully undergone bench‑to‑bedside transfer, which is probably due to inhibition of cardioprotection by comorbidities or associated pathological changes. Endothelial dysfunction (ED) is closely associated with most cardiovascular diseases and their typical comorbidities. Therefore, cardioprotective strategies should be examined under ED. It was previously demonstrated that dexmedetomidine (DEX) maintains its cardioprotective properties against ischemia/reperfusion (I/R) injury under hyperglycaemia in the setting of pre‑but not postconditioning, using a constant pressure Langendorff system. Under ED, cardioprotection by DEX preconditioning is also maintained using a constant flow mode, whereas this has not yet been investigated for postconditioning. Because DEX has vasoconstrictive properties, different haemodynamic conditions might influence the cardioprotective potential of DEX. Therefore, it was investigated whether pre‑ and postconditioning protocols with DEX used in constant pressure mode are transferable to constant flow mode and whether the cardioprotective effect of DEX is maintained under ED. The cardioprotective effect against I/R injury of pre‑ and post‑treatment with 3 nM DEX on isolated‑perfused hearts of male Wistar rats was analysed in constant flow mode. ED was induced by perfusion with Krebs‑Henseleit buffer containing 60 mM KCl. Heart function was assessed via pressure measurements in the left ventricle (LV) and infarct size (IS) via triphenyltetrazolium‑chloride staining. In constant flow mode, pre‑ and post‑treatment with DEX has no effect on IS and heart function compared with hearts treated with vehicle both under ED and under physiological conditions. In DEX pre‑treated hearts under ED, LV developed pressure is increased and contractility is improved after 60 min of reperfusion. Pre‑ and post‑treatment with DEX is not cardioprotective with the protocol used, while DEX pre‑treatment under ED has improving effects on heart function. Different hemodynamic conditions may modulate the cardioprotective properties of DEX, possibly due to its vasoconstrictive properties.
View Figures

Figure 1

Experimental protocol: Hearts of male
Wistar rats are pre-treated with 3 nM DEX or KHB as vehicle
(control; Con) for 5 min. For post-treatment, hearts are treated
for 10 min with 3 nM DEX with onset of reperfusion. ED is induced
by perfusion with KHB containing 60 mM KCl (K+); as a
control condition, perfusion with normal KHB is performed. DEX,
dexmedetomidine; KHB, Krebs-Henseleit-buffer; ED, endothelial
dysfunction.

Figure 2

Infarct sizes: Quantification of
infarct sizes from hearts pre-treated for 5 min or post-treated
(Post) for 10 min with 3 nM DEX or with vehicle
Krebs-Henseleit-buffer as control (Con) under healthy conditions or
ED. A representative heart slice stained with triphenyltetrazolium
chloride is shown for each group. The individual infarct sizes are
each shown with one data point. Data are presented as the mean ± SD
(n=6-7). One-way ANOVA revealed no significant differences between
groups (P>0.05). Dex, dexmedetomidine; ED, endothelial
dysfunction; LV, left ventricle.
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Copy and paste a formatted citation
Spandidos Publications style
De Luca-rohner S, Heinen A, Stroethoff M and Raupach A: Analysis of conditioning with dexmedetomidine under endothelial dysfunction in isolated perfused hearts. Biomed Rep 23: 136, 2025.
APA
De Luca-rohner, S., Heinen, A., Stroethoff, M., & Raupach, A. (2025). Analysis of conditioning with dexmedetomidine under endothelial dysfunction in isolated perfused hearts. Biomedical Reports, 23, 136. https://doi.org/10.3892/br.2025.2014
MLA
De Luca-rohner, S., Heinen, A., Stroethoff, M., Raupach, A."Analysis of conditioning with dexmedetomidine under endothelial dysfunction in isolated perfused hearts". Biomedical Reports 23.2 (2025): 136.
Chicago
De Luca-rohner, S., Heinen, A., Stroethoff, M., Raupach, A."Analysis of conditioning with dexmedetomidine under endothelial dysfunction in isolated perfused hearts". Biomedical Reports 23, no. 2 (2025): 136. https://doi.org/10.3892/br.2025.2014
Copy and paste a formatted citation
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Spandidos Publications style
De Luca-rohner S, Heinen A, Stroethoff M and Raupach A: Analysis of conditioning with dexmedetomidine under endothelial dysfunction in isolated perfused hearts. Biomed Rep 23: 136, 2025.
APA
De Luca-rohner, S., Heinen, A., Stroethoff, M., & Raupach, A. (2025). Analysis of conditioning with dexmedetomidine under endothelial dysfunction in isolated perfused hearts. Biomedical Reports, 23, 136. https://doi.org/10.3892/br.2025.2014
MLA
De Luca-rohner, S., Heinen, A., Stroethoff, M., Raupach, A."Analysis of conditioning with dexmedetomidine under endothelial dysfunction in isolated perfused hearts". Biomedical Reports 23.2 (2025): 136.
Chicago
De Luca-rohner, S., Heinen, A., Stroethoff, M., Raupach, A."Analysis of conditioning with dexmedetomidine under endothelial dysfunction in isolated perfused hearts". Biomedical Reports 23, no. 2 (2025): 136. https://doi.org/10.3892/br.2025.2014
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