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For general anesthesia, pre-oxygenation is routinely performed prior to intubation. It is well-known that ischemic/hypoxic preconditioning induces stem cell mobilization and protects against ischemia/reperfusion (I/R) injury. In this study, we investigated the effect of transient oxygenation on stem cell mobilization and I/R injury of the heart. Mice were exposed to 100% oxygen for 5 or 20 minutes. We evaluated the number of c-kit+ stem/progenitor cells and the levels of SDF-1α and VEGF in peripheral blood at 1, 3, 6, and 24 hours after oxygenation. We also induced I/R injury of the heart at 3 hours post-oxygenation for 5 minutes and then examined stem cell recruitment and fibrotic changes in the heart 3 or 14 days later. The number of c-kit+ cells in peripheral blood was significantly increased at 1 or 24 hours after oxygenation for either 5 or 20 minutes. Oxygenation for 5 or 20 minutes did not significantly change the SDF-1α level measured in plasma. However, the plasma VEGF level was decreased at 3 hours post-oxygenation for 20 minutes (p = 0.051). Oxygenation for 5 minutes did not significantly alter the fibrotic area or cell apoptosis. Although oxygenation for 5 minutes increased the number of c-kit+ cells in hearts damaged by I/R injury, this difference was not significant between groups due to large variation between individuals (p = 0.14). Although transient oxygenation induces stem cell mobilization, it does not appear to protect against I/R injury of the heart in mice. [ABSTRACT FROM AUTHOR]