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The Pathophysiology of Myocardial Infarction: From Coronary Occlusion to Clinical Consequence

1Coronary Supply and the Myocardial Oxygen Balance2Atherosclerotic Plaque Rupture and Coronary Thrombosis3Ischemia: Metabolic and Functional Consequences of Oxygen Deprivation4From Reversible Injury to Irreversible Cell Death5Inflammation, Healing, and Infarct Remodeling6Clinical Manifestations: ECG, Biomarkers, and Pump Dysfunction
Ischemia: Metabolic and Functional Consequences of Oxygen Deprivation

The metabolic switch: from oxidative phosphorylation to anaerobic glycolysis

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Start with the normal state: the heart is an obligate aerobe, getting about ninety percent of its ATP from oxidative phosphorylation. Oxygen is the terminal electron acceptor in the mitochondrial electron transport chain. When flow stops, that chain backs up and ATP production collapses. The cell switches to anaerobic glycolysis, but glycolysis yields only two ATP per glucose instead of roughly thirty. To keep even that going, the cell takes up more glucose and breaks down glycogen. Because pyruvate can't enter the mitochondria, lactate dehydrogenase converts it to lactate, regenerating NAD-plus so glycolysis continues. That reaction also releases protons, so the cell becomes acidic. The key point is that the substitute pathway is quantitatively inadequate, and the ATP deficit plus acidosis is what drives everything that follows.
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Why oxygen is non-negotiable

Cardiomyocytes are obligate aerobes: about 90% of their ATP comes from oxidative phosphorylation in mitochondria. Fatty acid beta-oxidation and pyruvate oxidation feed electrons into the electron transport chain, which drives ATP synthase. Oxygen is the terminal electron acceptor. Remove it, and the entire chain backs up.

The anaerobic substitute

With oxidative phosphorylation halted, the cell falls back on anaerobic glycolysis. Glycolysis yields a net 2 ATP per glucose, versus roughly 30 to 32 ATP from full oxidation. The cell compensates by increasing glucose uptake and mobilizing glycogen, but the yield per glucose is an order of magnitude lower.

Lactate production and acidosis

Pyruvate cannot enter mitochondria, so lactate dehydrogenase converts it to lactate: \[\text{pyruvate} + \text{NADH} + \text{H}^+ \rightarrow \text{lactate} + \text{NAD}^+\] This reaction regenerates NAD+ so glycolysis can continue, but it also releases protons. The accumulating lactate and H+ lower intracellular pH, producing ischemic acidosis.

The metabolic consequence

The switch to anaerobic glycolysis cannot meet the cell's ATP demand. The resulting ATP deficit and acidosis are the direct triggers for the ion pump failure and contractile failure that follow.

References

  1. [1]Myocardial ischemia: from disease to syndromencbi.nlm.nih.gov
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