Electrophysiological Changes During Cardiac Ischemia
When coronary blood flow is inadequate to support the oxygen needs of the myocardium (i.e., an ischemic state), tissue levels of oxygen fall, which leads to cellular hypoxia. Severe and prolonged hypoxia can ultimately lead to cellular death and total loss of electrical activity. Less severe hypoxia, or hypoxia of relatively short duration, will produce electrophysiological (and mechanical) changes in the heart. At the cellular level, depolarization occurs by several mechanisms. Hypoxic conditions lead to diminished intracellular concentrations of ATP. The loss of ATP leads to decreased activity of ATP-dependent transport systems, including the Na+/K+-ATPase pump that normally transports K+ into the cell and Na+ out of the cell. Because this pump is electrogenic, it normally produces hyperpolarizing currents. Decreased activity, therefore, leads to depolarization because of the loss of hyperpolarizing currents. More importantly, loss of pump activity prevents K+ from being pumped back into the cell so that its extracellular concentration increases as its intracellular concentration falls. This will cause membrane depolarization in accordance with the Nernst equation. Decreased ATP can also affect the movement of K+ through KATP channels, which open when there is reduced ATP. This leads to an outward movement of K+, which initially can lead to hyperpolarization; however, excessive outward movment of K+ will lead to an increase in extracelluar K+ and membrane depolarization.
Depolarization inactivates fast Na++ channels and thereby decreases action potential upstroke velocity (fast Na+ channels inhibited). This leads to decreased conduction velocity. Cellular depolarization and decreased conduction velocity can both contribute to arrhythmias that may require the use of antiarrhythmic drugs.
Injury currents flowing from the depolarized ischemic regions to normal regions result in the appearance of ST segment elevation or depression, depending upon whether the ischemic region is non-transmural, subendocardial (ST depression) or transmural (ST elevation). The former is usually associated with demand ischemia (e.g., exertional angina), whereas the latter is associated with supply ischemia (e.g., coronary occlusion).
For non-transmural ischemia, the ST segment depression occurs because when the ventricle is at rest and repolarized states, the depolarized, ischemic region generates electrical currents that are recorded by an overlying electrode. If the depolarizing currents are traveling toward the positive electrode, the baseline voltage prior to the QRS complex (which is normally isoelectric - i.e., zero volts) will be elevated. In contrast, when the ventricle becomes depolarized, all the muscle is depolarized so that zero voltage is recorded by the electrode as usual. Therefore, the net effect of the elevated baseline voltage is that the ST segment appears to be depressed relative to the baseline.
For transmural ischemia, the ST segment elevation occurs because when the ventricle is at rest and repolarized, the depolarized, ischemic region generates electrical currents that are traveling away from the positive electrode; therefore the baseline voltage prior to the QRS complex will be depressed. When the ventricle becomes depolarized, all the muscle is depolarized so that zero voltage is recorded by the electrode. Therefore, the net effect of the depressed baseline voltage is that the ST segment appears to be elevated relative to the baseline.