Restoration of coronary blood flow is essential for myocardial salvage in acute myocardial infarction (AMI), yet substantial injury and adverse remodeling often persist after successful reperfusion. Experimental ischemia–reperfusion models have identified dynamic innate immune responses involving neutrophils, monocytes, macrophages, and inflammatory signaling pathways that shape myocardial injury and repair under controlled conditions. In this review, we critically reappraise innate immune activation associated with myocardial ischemia and reperfusion by explicitly distinguishing experimental evidence from immune signatures observed in human myocardial infarction. While experimental studies demonstrate temporally structured and modifiable immune responses following brief ischemia and reperfusion, clinical myocardial infarction is typically characterized by prolonged ischemia, in which irreversible cardiomyocyte necrosis is largely established before reperfusion. Consequently, immune responses observed after revascularization predominantly reflect downstream consequences of ischemic injury and tissue repair rather than injury newly induced by reperfusion. Recognizing this distinction provides a refined framework for interpreting immune mechanisms and for guiding the rational development of immunomodulatory strategies in ischemic heart disease.
Zhang et al. (2026) studied this question.