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K 305 25 June 03

K 305 25 June 03. Cardiac Ischemia. local vs. global endocardial vs. transmural partial vs. total anoxia vs. ischemia ischemia – reperfusion injury. Cardiac Ischemia. Metabolic Effects ¯ b oxidation due to ¯ O 2 availability ¯ glucose oxidation increased  glycolysis

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K 305 25 June 03

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  1. K 305 25 June 03

  2. Cardiac Ischemia • local vs. global • endocardial vs. transmural • partial vs. total • anoxia vs. ischemia • ischemia – reperfusion injury

  3. Cardiac Ischemia • Metabolic Effects • ¯ b oxidation due to ¯ O2 availability • ¯ glucose oxidation • increased  glycolysis • increased glycogenolysis • ¯lactate oxidation-  lactate production

  4. Cardiac Ischemia • [K+]o • g of ATP-dependent K+ channels

  5. Cardiac Ischemia

  6. 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

  7. 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

  8. Hallmarks of Ischemia (con’t) • increased [Ca2+]i - causing contracture • OFR damage - lipid peroxidation • mitochondrial swelling • Neutrophil accumulation

  9. Contractile Dysfunction • Reversible • stunning • hibernation • Irreversible • necrosis • apoptosis

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