Myocardial Metabolism and Ischemia

Question 1

How is fatty acid carried throughout the body?

Answer 1

Albumin, VLDL, chylomicrons. Enter myocyte cytoplasm and attach to coA

Question 2

How are FAs released from their carriers?

Answer 2

LPL

Question 3

When is glucose used as an energy source in the myocardium?

Answer 3

The pumps use it normally and it’s used during ischemia and reperfusion

Question 4

What happens to glucose utilization during total ischemia?

Answer 4

Glycolysis is inhibited

• Acidosis inhibits PFK
• NADH inhibits GAPDH (dec pH)

Question 5

What happens to glucose utilization during mild ischemia?

Answer 5

Glucose uptake increases and there is an increase in glycolytic flux (inc in GLUT4 and PFK)

• NADH and Lactate accumulation regulate GAPDH
• GAPDH increases during repercussion and decreases in diabetes

Question 6

What are the cellular consequences of transient ischemia-stunning ?

Answer 6

Transient Ischemia- Stunning

• Diminished oxidative phosphorylation
• ATP partially buffered with phosphocreatine
• Acidosis
• Increased cytoplasmic Ca levels and buffering by mitochondria
• Restoration of oxygen renews oxidative phos, but leads to generation of oxy free radicals
• Proteolysis of a number of cardiac proteins

–>stunning can involve both free radical damage and proteolytic modification of cardiac proteins (like cleavage of troponin I which dec ca activation of the thin filament)

Question 7

What are the cellular consequences of prolonged ischemia-infarction?

Answer 7

Prolonged ischemia

• Severe depletion of ATP, PCr
• Intracellular acidosis
• Permanently impaired contractility
• Disrupted calcium homeostasis
• Reoxygenation results in oxygen free radical generation
• Cell death (apoptosis and necrosis)