The article discusses the mechanisms underlying acute protection from cardiac ischemia-reperfusion injury, focusing on the role of mitochondria in cell death and cardioprotection. During ischemia, ATP levels drop, leading to calcium accumulation and mitochondrial dysfunction. Reperfusion reintroduces oxygen, which can generate ATP but also increase reactive oxygen species (ROS), leading to mitochondrial permeability transition pore (MPT) opening and cell death. Mitochondria are central to both ATP production and ROS generation, and their dysfunction contributes to cell death. Cardioprotective mechanisms, such as ischemic preconditioning (PC), reduce calcium overload and MPT activation, thereby protecting cells. PC involves brief ischemia-reperfusion cycles that activate signaling pathways, including phosphoinositide-3-kinase (PI3K) and Akt, which mediate protection by reducing ATP breakdown and ROS production. Postconditioning, which involves brief reperfusion after ischemia, also provides protection by reducing MPT activation. The role of calcium and ROS in MPT activation is critical, as elevated calcium levels and ROS can trigger MPT opening, leading to cell death. The article also discusses the involvement of apoptosis, necrosis, and autophagy in ischemia-reperfusion injury, highlighting the complex interplay between these processes. Overall, the study emphasizes the importance of mitochondrial function and signaling pathways in cardioprotection, with a focus on acute protection mechanisms.The article discusses the mechanisms underlying acute protection from cardiac ischemia-reperfusion injury, focusing on the role of mitochondria in cell death and cardioprotection. During ischemia, ATP levels drop, leading to calcium accumulation and mitochondrial dysfunction. Reperfusion reintroduces oxygen, which can generate ATP but also increase reactive oxygen species (ROS), leading to mitochondrial permeability transition pore (MPT) opening and cell death. Mitochondria are central to both ATP production and ROS generation, and their dysfunction contributes to cell death. Cardioprotective mechanisms, such as ischemic preconditioning (PC), reduce calcium overload and MPT activation, thereby protecting cells. PC involves brief ischemia-reperfusion cycles that activate signaling pathways, including phosphoinositide-3-kinase (PI3K) and Akt, which mediate protection by reducing ATP breakdown and ROS production. Postconditioning, which involves brief reperfusion after ischemia, also provides protection by reducing MPT activation. The role of calcium and ROS in MPT activation is critical, as elevated calcium levels and ROS can trigger MPT opening, leading to cell death. The article also discusses the involvement of apoptosis, necrosis, and autophagy in ischemia-reperfusion injury, highlighting the complex interplay between these processes. Overall, the study emphasizes the importance of mitochondrial function and signaling pathways in cardioprotection, with a focus on acute protection mechanisms.