Ischemia is the pathophysiologic state when blood flow to a tissue bed is reduced to a level that is inadequate to supply the oxygen and metabolic nutrient requirements of the tissue.
Ischemia in tissues
Þ Hypoxia (insufficient supply of oxygen to support oxidative metabolism leading to anaerobic metabolism); accumulation of toxic metabolites (lactate) that are not "washed out" of tissue by adequate blood flow including the development of acidosis.
is the restoration of adequate blood flow after a period of ischemia. However, reperfusion injury can occur.
Effect of Myocardial Ischemia: Myocardial Metabolism
Normal myocardial cells derive 2/3 of their energy from lipid metabolism, most of the rest from carbohydrates.
During ischemia there is a shift to greater carbohydrate metabolism.
Abnormalities of myocardial metabolism during ischemia are:
ATP and high energy phosphate, i.e., creatinine phosphate, production and storage
lactate production and accumulation of ACYL carnitine
Intracellular H+, NADH accumulation = acidosis
Intracellular calcium overload
Free radial oxygen production and accumulation
High levels of ischemia (when ATP and creatinine phosphate are <30% normal)
Þ irreversible structural damage Þ sarcolemmal damage ("necrosis") with leakage of intracellular chemicals.
Presently, the most important intracellular "leaked" chemicals ("cardiac enzymes") which are elevated in the blood during myocardial ischemia leading to cellular necrosis are Troponin I or T (can be in bloodstream up to 2 weeks), creatinine Kinase (CK) and its MB isomere (CKMB). There are other chemicals (myoglobin, lactate dehydrogenase) that can also be used; however, these are less specific for ischemic cardiac damage and "necrosis" of cardiac cells.
Serum markers – CK-MB (heart muscle) isoforms (
Ý 6-12 hours, drops in 3 days), Myoglobin (first released, any skeletal muscle injury so nonspecific), Troponin T (cardiac damage, any injury of the heart, rises 6-12 days, stays in blood stream for 10-14 days – more specific), LDI (lactate dehydrogenase, Ý in 2 days, decrease in 6 days)
Effects of Myocardial Ischemia: Mechanical Abnormalities
Effects of Ischemia on Contractility
affects both systole and diastole almost immediately due to reduction of high-energy phosphate compounds
Influx of intracellular calcium
Þ Ý intramitochondrial calcium but ß SR calcium Þ ß contractility
intracellular sodium due to inhibition of Na+ pump Þ Na+ competes with Ca++ Þ ß contractility
Þ ß sensitivity of the cardiac contractile proteins and alters the function of important transport enzymes.
Myocardial ischemia is a local phenomena, not global. During systole an ischemic area can undergo:
hypokinesis – reduced contraction
akinesis – no contraction
dyskinesis – bulging outward
echocardiography, nuclear scanning, or contrast ventriculograms can be used to look for signs of ischemia.
Diastolic problems – due to limited release of Ca++ from contractile proteins, which is impaired due to ischemia.
Heart becomes stiff
Þ increased LVEDP Þ pulmonary congestion
Increased diastolic stiffness
Þ audible S4 present – give nitro, can alleviate
can get mitral insufficiency
Long-term effects on contractility
Prolonged myocardial ischemia
Þ permanently injured myocardial tissue (necrosis) Þ acute myocardial infarction, or slowly cause an ischemic cardiomyopathy
– severe chronic level of myocardial ischemia without necrosis. Reversal of dysfunction will occur after revascularization.
– severe acute level of ischemia followed by reperfusion before a large amount necrosis occurs can lead to a prolonged period of contractile abnormality that slowly recovers.
Clinically, it is important to distinguish between ischemic episodes which can be helped by revascularization techniques (stunned, hibernating) and those that cannot (acute MI, or ischemic cardiomyopathy).
Stress Testing can be used to detect ischemia: Look for ST changes (not always diagnostic); wall motion depression (on echo);