If a coronary artery becomes blocked, blood flow to the heart is reduced (hint:

Question

If a coronary artery becomes blocked, blood flow to the heart is reduced (hint: lookup myocardial infarction).

a) How does lack of blood flow affect oxidative metabolism and why?

b) What will happen to the pH of the affected heart cells?

c) What will happen to levels of ATP in the affected heart cells?

d) What will happen to calcium levels in the cytosol of the affected heart cells and why?

e) What will happen to the gap junctions between the affected heart cells and other cells?

f) What will happen to the conduction of electrical signals across the affected tissue?

Explanation / Answer

If impaired blood flow to the heart lasts long enough, it triggers a process called the ischemic cascade; the heart cells in the territory of the blocked coronary artery die (infarction), chiefly through necrosis, and do not grow back. A collagen scar forms in their place. When an artery is blocked, cells lack oxygen, needed to produce ATP in mitochondria. ATP is required for the maintenance of electrolyte balance, particularly through the Na/K ATPase. This leads to an ischemic cascade of intracellular changes, necrosis and apoptosis of affected cells.

Cells in the area with the worst blood supply, just below the inner surface of the heart (endocardium), are most susceptible to damage. Ischemia first affects this region, the subendocardial region, and tissue begins to die within 15–30 minutes of loss of blood supply. The dead tissue is surrounded by a zone of potentially reversible ischemia that progresses to become a full-thickness transmural infarct.

ATP levels and intracellular pH decrease as a result of anaerobic metabolism and lactate accumulation. As a consequence, ATPase-dependent ion transport mechanisms become dysfunctional, contributing to increased intracellular and mitochondrial calcium levels (calcium overload), cell swelling and rupture, and cell death by necrotic, necroptotic, apoptotic, and autophagic mechanisms.

The gap junctions between the affected heart cells will uncouple. Gap junctions play a significant role in the longitudinal and transverse propagation of signals. Due to the loss of ATP, the depolarization of the fibers, and the intracellular Na+ and Ca2+ overload with concomitant acidification as well as the accumulation of lysophosphoglyceride and arachidonic acid metabolites, propagation of action potentials will be impaired by two factors: (a) reduced sodium channel availability and (b) gap junction uncoupling. While gap junction uncoupling leads to predominant transverse uncoupling, reduced intracellular Na availability results in impaired longitudinal conduction.

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