1. K 305
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4. Cardiac Ischemia local vs. global endocardial vs. transmural
partial vs. total
anoxia vs. ischemia
ischemia – reperfusion injury
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5. Cardiac Ischemia Metabolic Effects
¯ b oxidation due to ¯ O2 availability
¯ glucose oxidation
increased  glycolysis
increased glycogenolysis
¯ lactate oxidation -  lactate production
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6. Cardiac Ischemia
[K+]o
g of ATP-dependent K+ channels
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7. Cardiac Ischemia
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8. Hallmarks of Ischemia KATP channels octamers
four pore forming a subunits
inward rectifier channels Kir 6.1 or Kir 6.2
four regulatory b subunits
sulphonylurea receptors SUR1 or SUR2
Different combinations of Kir and SUR subunits generate tissue-specific KATP channel subtypes
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10. 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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11. Hallmarks of Ischemia (con’t)
increased [Ca2+]i - causing contracture
OFR damage - lipid peroxidation
mitochondrial swelling
Neutrophil accumulation
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12. Contractile Dysfunction
Reversible
stunning
hibernation
Irreversible
necrosis
apoptosis
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