Lecture 21: myocardial ischemia pathology

Question 1

Why is the subendocardium more susceptible to ischemia?

Answer 1

anything downstream of block will be affected, blood vessel in transmural runs from epi to endocardium.

however countered by preconditioning.

Question 2

Discuss the consequences of ischemia

1) metabolic effects
2) burst of free radicals
3) increase in extracellular potassium
4) electrical remodelling
5) reduced contraction force
6) impaired calcium handling
7) post-ischemic contractile dysfunction

Answer 2

1) metabolic effects: lack of O2 means no beta-oxidation. therefore no ATP produced, this means more lactic acid buildup, H+ increases, inhibits lactate/H+ cotransporter
2) burst of free radicals (supraoxide/H2O2) from reactive oxygen/nitrogen species causes damage to tissue, peroxidation of lipid membranes
3) increase in extracellular potassium: decreased activity of Na/K ATPase, more conductance through Katp channels. raises RMP. cardioprotective effect by decreasing length of AP by increasing repolarization, therefore less Ca entry.
4) electrical remodelling: increase in H+ decreases Ca, Na, and K currents.
5) Reduced contraction force. lower Ca current, decreased sensitivity in troponin, less ATPase activity, less cross-bridge cycling.
6) Impaired calcium handling: less Ca entry, Ca release from cytosolic buffer, less SR release, less Ca extruded by NCX, Ca enters through NCX, less SR uptake. leads to cytoplasmic overload, possibly apoptosis, also tonic contractile state, activates enzymes like calpain that breaks down protein
7) post-ischemic contractile dysfunction: doesn’t work for a couple of days, if hibernation = months. needs to revascularize, deccreased contractility. if permanent, leads to necrosis/apoptosis.