What are the microscopic findings of myocardial infarction, including the cells involved?

Microscopic Findings of Myocardial Infarction

Myocardial infarction is characterized pathologically by coagulation necrosis and/or contraction band necrosis, with polymorphonuclear leukocytes defining acute infarction, followed by mononuclear cells and fibroblasts during healing, and ultimately scar tissue formation. 1

Fundamental Pathologic Features

Cell death occurs primarily through oncosis (coagulative necrosis) as the dominant mechanism, with apoptosis playing a lesser but significant role. 1, 2 Both forms of cell death coexist in every myocardial infarction, though their relative proportions and timing differ. 3

Key Distinguishing Features:

• Necrotic myocytes rapidly disintegrate and lose membrane integrity, evoking acute inflammation 3
• Apoptotic myocytes retain membrane integrity and do not trigger acute inflammation 3
• Complete necrosis of all at-risk myocardial cells requires at least 2-4 hours or longer, depending on collateral circulation, intermittent occlusion patterns, and individual oxygen demand 1, 2

Temporal Evolution: The Microscopic Timeline

Hyperacute Phase (<6 hours)

• Waviness of myocardial fibers may be the only detectable microscopic finding in very early sudden death 1
• Minimal or no polymorphonuclear leukocytes are present if death occurs within 6 hours of onset 1
• Standard microscopic examination requires approximately 6 hours before myocardial necrosis becomes identifiable 1, 2
• Apoptosis appears as the early and predominant form of cell death, visible within hours before coagulative necrosis becomes apparent 4
• Apoptotic changes are particularly prominent in myocytes containing contraction bands, which occur predominantly in reperfused regions 4

Acute Phase (6 hours to 7 days)

The presence of polymorphonuclear leukocytes is the defining histologic feature of acute myocardial infarction. 1 This inflammatory infiltrate serves to clear dead cells and matrix debris from the injured myocardium. 5, 6

Cellular Components:

• Polymorphonuclear leukocytes (neutrophils) dominate the acute inflammatory response 1
• Necrotic cardiomyocytes release danger signals (interleukin-1α and RNA) that trigger the inflammatory cascade 5
• Coagulative necrosis extends from subendocardium to subepicardium in a "wavefront" pattern over 2-4 hours 2

Healing Phase (7 to 28 days)

The presence of mononuclear cells and fibroblasts with absence of polymorphonuclear leukocytes characterizes healing infarction. 1

Cellular Components:

• Macrophages exhibit significant heterogeneity and phenotypic plasticity, orchestrating the reparative response 5
• Phagocytosis of apoptotic cells occurs through engulfment by either neighboring myocytes or macrophages (predominantly the latter) 3
• Inhibitory lymphocytes play a crucial role in negative regulation of inflammation by modulating macrophage and fibroblast phenotype 5
• Fibroblasts begin converting to myofibroblasts under the influence of transforming growth factor-β and renin-angiotensin-aldosterone system activation 6
• Mononuclear inflammatory cells replace neutrophils 1

Healed Phase (≥29 days)

Scar tissue without cellular infiltration manifests as the healed infarction. 1 The entire process leading to a healed infarction usually takes at least 5-6 weeks. 1, 2

Special Microscopic Features with Reperfusion

Reperfusion significantly alters the microscopic appearance, producing myocytes with prominent contraction bands and large quantities of extravasated erythrocytes. 1, 2

• Contraction bands become prominent as calcium rushes into dying cells, causing hypercontraction of myofibrils 2
• This pattern differs markedly from non-reperfused infarction and must be recognized to avoid misinterpretation 1
• Apoptosis is accelerated in reperfused myocardium, appearing primarily in cells with contraction bands 4

Critical Diagnostic Pitfalls

Timing Discordance

Clinical and electrocardiographic timing may not correspond exactly with pathological timing. 1, 7 The ECG may show evolving ST-T changes and biomarkers may remain elevated when pathologically the infarction is already in the healing phase. 1, 7

Underestimation of Infarct Size

Because apoptotic cells retain membrane integrity, enzymatic diagnosis based on intracellular enzyme release (troponin, CK-MB) reflects only necrosis. 3 Measurement of any intracellular enzyme consequently always underestimates the extent of myocardial infarction, often by a large margin, as apoptotic cell death does not release these markers. 3

Overwhelmed Phagocytic Capacity

In many apoptotic areas, the phagocytic capacity becomes overwhelmed, resulting in large pools of apoptotic bodies lying free in the extracellular space. 3 This morphological progression from apoptosis to necrosis may depend upon exceeding the local capacity for phagocytosis of apoptotic cells. 3