The effects of metoprolol on hypoxia- and isoflurane-induced cardiac late-phase preconditioning

作者：Goetzenich A^*; Roehl A B; Moza A; Srecec D; Beyer C; Arnold S; Hein M

来源：Acta Anaesthesiologica Scandinavica, 2011, 55(7): 862-869.

DOI：10.1111/j.1399-6576.2011.02455.x

Background: The detrimental effects of metoprolol on early-phase preconditioning (pc) have been proven. The late phase of pc is mediated via gene transcription and cyclooxygenase-2 (COX-2) was identified as one of the key mediators. The effect of metoprolol on this is yet unknown as is its effect on cellular energy metabolism and reactive oxygen species (ROS) creation.
Methods: Cardiomyocytes from neonatal rats were cultured and randomly assigned to four pairs of treatment groups. In each pair, one group received metoprolol at a dose of 0.5 mu g/ml medium. One pair served as a control; the others were subjected to 5h of hypoxia 24 h after either hypoxia-induced, isoflurane-induced or no pc. Cell survival was measured with a redox indicator for cell metabolism. COX-2 transcription, ATP and ROS creation were measured.
Results: Whereas both ischemic and isoflurane pc produced mild beneficial effects (48.8 +/- 6.0% and 48.2 +/- 7.8% of surviving cells, respectively) compared with unpreconditioned controls (35.9 +/- 7.9%, P <0.01 for both), adding metoprolol was detrimental for both kinds of pc ( hypoxia: 31.5 +/- 3.5%; isoflurane: 25.7 +/- 3.8%, P < 0.001) but not in the unpreconditioned group (39.4 +/- 4.9%). mRNA for COX-2 was up to 10-fold elevated in pc cells. This induction was suppressed by metoprolol. Hypoxic and isoflurane- induced pc showed significant differences in ATP balance and ROS generation.
Conclusion: Metoprolol abolishes the protection of both isoflurane- and hypoxia-induced late-phase pc in our model. This effect is accompanied by the blockade of COX-2 induction. The differences between hypoxic and isoflurane pc in ATP and ROS creation allow to presume distinct pathways on the mitochondrial level.

• 出版日期2011-8