Review Question - QID 100654

Extensive granulation tissue replacing dead myocardium and early neovascularization are histologic changes expected 10-14 days after a myocardial infarction (MI).

The timeline for histologic changes following myocardial infarction is a topic commonly tested on USMLE examinations. Light microscopy changes post-MI are as follows:
4-12 hours: coagulation necrosis, edema, hemorrhage
12-24 hours: hypereosinophilia, coagulation necrosis, contraction bands, beginning neutrophil emigration
2-4 days: extensive neutrophil infiltration and continued coagulation necrosis
5-10 days: macrophage infiltration and phagocytosis of dead cells; early granulation tissue appears
10-14 days: extensive granulation tissue and revascularization begins
2 weeks-2 months: fibroblast deposition of type I collagen, with ongoing contraction of the scar and decreased cellularity of the tissue
> 2 months: completed scar formed of dense collagen

Turakhia discusses the pathophysiology and prevention of sudden cardiac death. Assessment of left ventricle ejection fraction is the most important factor in identifying patients at increased risk of sudden cardiac death. Ejection fraction of less than 35% is an indication for prophylactic implantable cardioverter-defibrillator (ICD) placement.

van Nieuwenhoven et al. discuss the role of cardiac fibroblasts in the reparative process following an MI. In the early, acute phase fibroblasts secrete proinflammatory chemokines and cytokines. During the granulation phase, fibroblasts produce matrix metalloproteinases and pro-angiogenic factors to aid in revascularization. Finally, fibroblasts as well as myofibroblasts play a significant role in the development of fibrosis and mature scar formation.

Figure A is 2 weeks post-MI and shows chronic inflammation with the presence of granulation tissue, hemosiderin-filled macrophages, as well as the presence of fibroblasts with early evidence of collagen deposition.

Illustration A shows the beginning of neutrophilic infiltration at 24 hours post-MI; viable tissue is on the left and the infarcted segment is on the right with the neutrophilic infiltrate of greatest concentration at the border between the two.
Illustration B depicts contraction band necrosis, a finding commonly seen 12-24 hours post-MI.
Illustration C shows post-MI scar formation with collagen deposition highlighted with the blue trichrome stain.

Incorrect Answers:
Answer 1: Hypereosinophilia, contraction bands, and early coagulative necrosis would be expected 12-24 hours post-MI; neutrophil emigration typically begins after 24 hours.

Answer 2: 2-4 days post-MI is associated with extensive coagulation necrosis and neutrophilic infiltrate.

Answer 3: Macrophage emigration and infiltration as well as early granulation tissue are expected 5-10 days post-MI.

Answer 5: 2 weeks to 3 months post-MI is characterized by collagen deposition by fibroblasts and dense scar formation.