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

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 μg/ml medium. One pair served as a control; the others were subjected to 5 h 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