Irreversible necrosis releases intracellular contents — mitochondrial DNA, ATP metabolites, and damaged proteins — that act as danger signals and activate the complement and cytokine cascades. Within hours, neutrophils marginate in the microvasculature of the infarct border and migrate into the necrotic zone, peaking at roughly 24–72 hours. They release proteases, myeloperoxidase, and reactive oxygen species that digest dead myocytes and debris. This clearance is necessary for repair, but the same enzymes can extend injury into borderline-viable tissue at the border zone.
Monocytes arrive slightly later and differentiate into macrophages, which dominate from about day 3 to day 7. Macrophages are not a single population: an early pro-inflammatory phenotype continues phagocytosis of necrotic debris, while a later reparative phenotype secretes transforming growth factor-beta, vascular endothelial growth factor, and fibroblast growth factors that suppress inflammation and initiate angiogenesis and fibroblast recruitment. The transition between these phenotypes is the switch from demolition to reconstruction, and it is regulated by signals such as phagocytosis of apoptotic neutrophils and lipid mediators.
The clinical correlate is timing: the inflammatory phase overlaps with the period of greatest risk for arrhythmia and for infarct expansion, because the wall is being digested while not yet reinforced by collagen.