Abstract | OBJECTIVES: The protective effects of late-phase preconditioning can be triggered by several stimuli. Unfortunately, the transfer from bench to bedside still represents a challenge, as concomitant medication or diseases influence the complex signalling pathways involved. In an established model of primary neonatal rat cardiomyocytes, we analysed the cardioprotective effects of three different stimulating pharmaceuticals of clinical relevance. The effect of additional β-blocker treatment was studied as these were previously shown to negatively influence preconditioning. METHODS: RESULTS: Five hours of hypoxia reduced cell survival in unpreconditioned control cells to 44 ± 4%. Surviving cell count was significantly higher in cells preconditioned either by 2 × 15 min isoflurane (70 ± 16%; P = 0.005) or by xenon (59 ± 8%; P = 0.049). Xenon-preconditioned cells showed a significantly elevated content of VEGF (0.025 ± 0.010 IDV [integrated density values when compared with GAPDH] vs 0.003 ± 0.006 IDV in controls; P = 0.0003). The protein expression of HIF-1α was increased both by levosimendan (0.563 ± 0.175 IDV vs 0.142 ± 0.042 IDV in controls; P = 0.0289) and by xenon (0.868 ± 0.222 IDV; P < 0.0001) pretreatment. A significant elevation of mRNA expression of iNOS was measureable following preconditioning by xenon but not by the other chosen stimuli. eNOS mRNA expression was found to be suppressed by β-blocker treatment for all stimuli. In our model, independently of the chosen stimulus, β-blocker treatment had no significant effect on cell survival. CONCLUSIONS: We found that the stimulation of late-phase preconditioning involves several distinct pathways that are variably addressed by the different stimuli. In contrast to isoflurane treatment, xenon-induced preconditioning does not lead to an increase in COX-2 gene transcription but to a significant increase in HIF-1α and subsequently VEGF.
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Authors | Andreas Goetzenich, Nima Hatam, Stephanie Preuss, Ajay Moza, Christian Bleilevens, Anna B Roehl, Rüdiger Autschbach, Jürgen Bernhagen, Christian Stoppe |
Journal | Interactive cardiovascular and thoracic surgery
(Interact Cardiovasc Thorac Surg)
Vol. 18
Issue 3
Pg. 321-8
(Mar 2014)
ISSN: 1569-9285 [Electronic] England |
PMID | 24351506
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adrenergic beta-1 Receptor Antagonists
- Hif1a protein, rat
- Hydrazones
- Hypoxia-Inducible Factor 1, alpha Subunit
- Pyridazines
- RNA, Messenger
- Vascular Endothelial Growth Factor A
- vascular endothelial growth factor A, rat
- Simendan
- Xenon
- Isoflurane
- Nitric Oxide Synthase Type II
- Nos2 protein, rat
- Metoprolol
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Topics |
- Adrenergic beta-1 Receptor Antagonists
(pharmacology)
- Animals
- Animals, Newborn
- Cell Hypoxia
- Cell Survival
(drug effects)
- Cells, Cultured
- Cytoprotection
- Hydrazones
(pharmacology)
- Hypoxia-Inducible Factor 1, alpha Subunit
(genetics, metabolism)
- Isoflurane
(pharmacology)
- Metoprolol
(pharmacology)
- Myocytes, Cardiac
(drug effects, metabolism, pathology)
- Nitric Oxide Synthase Type II
(genetics, metabolism)
- Pyridazines
(pharmacology)
- RNA, Messenger
(metabolism)
- Rats
- Rats, Wistar
- Signal Transduction
(drug effects)
- Simendan
- Time Factors
- Up-Regulation
- Vascular Endothelial Growth Factor A
(genetics, metabolism)
- Xenon
(pharmacology)
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