Reperfusion injury after myocardial ischemia is predominantly mediated by which mechanism?

• A Massive influx of calcium and burst generation of reactive oxygen species (ROS) upon reflow ✓
• B Re-accumulation of intracellular glycogen depleting ATP
• C Apoptosis triggered solely by re-oxygenation of cardiomyocytes
• D Microthrombus formation in capillaries blocking reflow permanently

Explanation

Reperfusion injury occurs because the sudden restoration of oxygen to ischemic (but still potentially viable) cells generates a burst of ROS via xanthine oxidase and mitochondrial electron transport chain dysfunction. Simultaneously, cytosolic calcium overload (due to impaired Na+/K+ ATPase and Na+/Ca2+ exchange reversal) activates phospholipases and endonucleases and opens the mitochondrial permeability transition pore (mPTP), committing cells to death. Neutrophil-mediated oxidative damage also contributes. This is distinct from the ischemic injury itself, which is primarily ATP depletion and acidosis.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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