From the Guidelines
Mitochondrial swelling and glycogen granule depletion in the ischemic region during an acute coronary occlusion are primarily caused by the shift from aerobic to anaerobic metabolism, leading to energy depletion, ionic disturbances, and acidosis. When blood flow is restricted, oxygen supply becomes inadequate, forcing cells to shift from aerobic to anaerobic metabolism, as noted in the context of myocardial infarction mechanisms 1. This metabolic switch causes rapid accumulation of lactic acid and hydrogen ions, creating an acidic environment that disrupts normal cellular function.
Key Metabolic Events
- ATP production decreases dramatically as oxidative phosphorylation fails, leading to dysfunction of ATP-dependent ion pumps, particularly the Na+/K+ ATPase.
- The resulting ionic imbalance causes sodium and calcium influx into cells, while potassium leaks out.
- Calcium overload is especially damaging, as it enters mitochondria and triggers opening of the mitochondrial permeability transition pore, causing mitochondrial membrane depolarization, further impairing ATP production, and leading to mitochondrial swelling.
- Simultaneously, glycogen stores are rapidly depleted as cells desperately attempt to generate ATP through glycolysis in the absence of oxygen, a scenario consistent with the pathophysiological mechanisms of myocardial infarction described in 1 and 1. The combination of energy depletion, ionic disturbances, and acidosis ultimately leads to cellular injury and, if prolonged, cell death in the affected myocardium.
From the Research
Metabolic Events Causing Mitochondrial Swelling and Depletion of Glycogen Granules
The metabolic events that most likely cause mitochondrial swelling and depletion of glycogen granules in the ischemic region during an acute coronary occlusion are:
- Cessation of aerobic metabolism 2
- Depletion of creatine phosphate (CP) 2
- Onset of anaerobic glycolysis 2
- Accumulation of glycolytic products, such as lactate and alpha glycerol phosphate (alpha GP) 2
- Decrease in ATP levels and intracellular pH due to anaerobic metabolism and lactate accumulation 3
- Dysfunction of ATPase-dependent ion transport mechanisms, contributing to increased intracellular and mitochondrial calcium levels (calcium overload) 3
- Cell swelling and rupture due to calcium overload and dysfunction of ion transport mechanisms 3
Key Metabolic Changes
The key metabolic changes that occur during ischemia include:
- Depletion of glycogen granules due to anaerobic glycolysis 2
- Mitochondrial swelling due to calcium overload and oxidative stress 2, 3, 4
- Accumulation of reactive oxygen species upon reperfusion, exacerbating ischemic injury 3
Biochemical Alterations
The biochemical alterations that occur during ischemia and reperfusion include: