Antioxidant Cardioprotection in Acute Myocardial Infarction: From Mechanisms to Therapeutic Strategies

Acute myocardial infarction (AMI) is one of the main causes of mortality worldwide. Currently, the most effective treatment is percutaneous coronary angioplasty (PCA). However, paradoxically, the restoration of blood flow induces myocardial reperfusion injury (MRI), contributing up to 50% of the final infarct size. Oxidative stress, characterized by a burst of reactive oxygen species (ROS) following reperfusion, plays a fundamental role in its pathophysiology, causing inflammation, endothelial dysfunction, and cell death mainly through autophagy, apoptosis, ferroptosis, necroptosis, and pyroptosis. To mitigate these injury mechanisms, numerous antioxidant strategies have been evaluated using both in vitro and in vivo models with promising results, but limited benefit when tested in humans. Several antioxidants have biological properties that counteract ROS-induced damage by acting as ROS scavengers, metal chelators, and antioxidant enzyme enhancers. In this review, we focus on the mechanisms by which oxidative stress induces cell death after AMI and highlight the most promising therapeutic antioxidant agents that could provide comprehensive protection against MRI. A multitarget cardioprotective strategy, combining interventions with strong preclinical evidence, could provide a more effective approach for reducing MRI. Our study aims to bridge the gap between basic and clinical research and explore the potential clinical applications of antioxidants.