As of yet, only a few strategies to prevent myocardial reperfusion injury have been tested clinically. In the first minutes of reperfusion, the myocardium can be damaged by contracture development, causing mechanical stiffness, tissue necrosis, and the “stone heart” phenomenon. Reperfusion-induced contracture can have two different causes, namely, Ca²⁺overload–induced contracture or rigor-type contracture. Ca²⁺ contracture results from rapid re-energization of contractile cells with a persistent Ca²⁺ overload. Strategies to prevent this type of injury are directed at cytosolic Ca²⁺ control or myofibrillar Ca²⁺ sensitivity. Rigor-contracture occurs when re-energization proceeds very slowly. It does not depend on Ca²⁺ overload. It may be prevented by strategies improving early mitochondrial reactivation