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K 305

25 June 03

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Cardiac Ischemia

•local vs. globalendocardial vs. transmural

•partial vs. total

•anoxia vs. ischemia

•ischemia – reperfusion injury

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Cardiac Ischemia

Metabolic Effects

• oxidation due to O2 availability

• glucose oxidation

• increased  glycolysis

• increased glycogenolysis

• lactate oxidation - lactate production

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Cardiac Ischemia[K+]o

• g of ATP-dependent K+ channels

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Cardiac Ischemia

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Hallmarks of Ischemia

KATP channels

•octamers

• four pore forming subunits

inward rectifier channels Kir 6.1 or Kir 6.2

• four regulatory subunits

sulphonylurea receptors SUR1 or SUR2

Different combinations of Kir and SUR subunits generate tissue-specific KATP channel subtypes

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Cardiac Ischemia[K+]o

• g of ATP dependent K+ channels

• activity of Na-K pump

• gK causes Em (hyperpolarization)

• AP duration - Ca influx - contractility

• demand for MVO2 – cardioprotective

• gK will lead to [K+]o - which depolarizes

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•increased [Ca2+]i - causing contracture •OFR damage - lipid peroxidation

•mitochondrial swelling

•Neutrophil accumulation

Hallmarks of Ischemia (con’t)

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Reversible•stunning•hibernation

Irreversible•necrosis•apoptosis

Contractile Dysfunction