1640: CONTROLLED REPERFUSION AND ANTIOXIDANT THERAPIES: A REVIEW OF NOVEL APPROACHES TO REPERFUSION INJURY

Introduction: Ischemia-reperfusion injury (IRI) arises when oxygen re-exposure after ischemia triggers a burst of reactive oxygen species (ROS), provoking inflammation and cell death. Conventional reperfusion with fully oxygenated blood may therefore intensify tissue damage. Two physiologically based countermeasures have emerged: (1) controlled reperfusion that titrates oxygen delivery and (2) peri-operative antioxidant infusion. We reviewed recent evidence to test the hypothesis that these strategies attenuate ROS-mediated injury and improve clinical outcomes compared with standard reperfusion. Methods: A literature review was conducted using experimental studies, clinical trials, and meta-analyses investigating (1) controlled hypoxemic reperfusion, and (2) antioxidant administration, including agents such as N-acetylcysteine, iron/copper chelators, and high-dose intravenous vitamin C, in various IRI models, including stroke, cardiac surgery, and flap ischemia. Results: Controlled reperfusion blunted the reoxygenation-induced oxidative burst, preserved mitochondrial function, and improved post-ischemic cardiac output in pre-clinical models. Ultrasound-mediated acoustic droplet vaporization reduced PaO2 during flow restoration and limited lipid peroxidation. Hyperoxic reperfusion also improved outcomes by relieving residual tissue hypoxia rather than reducing ROS; the AMIHOT-1/2 trials exhibited smaller infarct sizes and better wall-motion scores than controls. High-dose perioperative IV vitamin C significantly reduced postoperative atrial fibrillation. Antioxidant therapy lowered serum troponins, rate of post-MI atrial fibrillation, ventilation times, and hospital stays, although its effects on mortality and stroke remain inconclusive. Conclusions: Controlled reperfusion and antioxidant therapies show promise in attenuating oxidative stress in IRI and improving outcomes post-ischemia. Incongruent benefits in both hypoxic and hyperoxic reperfusion indicate the possible utility of both as a new paradigm in reperfusion, with early hypoxic reperfusion to minimize ROS damage, followed by hyperoxic reperfusion to reverse hypoxemic damage. Prospective trials should identify the optimal combination of hypoxic, hyperoxic, and antioxidant reperfusion to limit IRI.