Reactive oxygen species (ROS) mediate intermittent hypoxia conditioning (IHC)‐induced cardioprotection

Background: IHC protects canine myocardium from ischemia‐reperfusion injury. Hypothesis: ROS produced during cyclic hypoxia‐reoxygenation evoke IHC‐induced cardioprotection. Methods: Dogs underwent IHC [5–8 cycles of 5–10 min hypoxia (9.5–10% FIO 2 ) + 4 min normoxia], uninterrupted hypoxia conditioning (UHC) lacking intermittent normoxia, or consumed antioxidant N ‐acetylcysteine (NAC; 250 mg/kg) 2 h before IHC, for 20 d. On day 21, the left anterior descending coronary artery was occluded for 1 h and reperfused for 5 h. Infarct size (IS) and area at risk (AAR) were measured by standard dyeing techniques; arrhythmias were detected by lead II ECG and scored. Results (Table: mean ± SE; ∗P< 0.001 v non‐hypoxic sham; † P < 0.001 v IHC): IHC was remarkably cardioprotective, but UHC failed to mitigate infarction or arrhythmias, and NAC blocked the protection. Conclusion: ROS produced during IHC sessions are essential for development of robust cardioprotection. (NIH support: HL‐064785, HL‐071684)