 Acute myocardial infarction, AMI, is a leading cause of morbidity and mortality, with reperfusion strategies being the current standard treatment. Despite these treatments, however, there is still a risk of paradoxical cardiac dysfunction, known as ischemic reperfusion injury, II, which can lead to sudden death. This paper explores the pathophysiology of II, focusing on the potential roles of the calpain system, oxidative nitrosative stress, and matrix metalloproteinase activity. Understanding the pathophysiology of II could help improve outcomes for patients suffering from AMI, as well as provide insight into sudden deaths following AMI. This article was authored by Margaritoneri, Irene Riezzo, Natasha Pascale, and others.