Cellular electrophysiological changes

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
causes 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 movement of K+ will lead to an increase in extracelluar K+ and
membrane depolarization. Depolarization is accompanied by reduced action potential duration,
and therefore earlier repolarization.
Depolarization inactivates fast Na++ channels and thereby decreases action potential upstroke
(phase 0) velocity. This leads to decreased conduction velocity. Cellular depolarization,
shortened action potentials, and decreased conduction velocity can contribute
to arrhythmias that may require the use of antiarrhythmic drugs.
T wave abnormalities
T waves are normally upright because the last ventricular cells to depolarize are subepicardial
cells, which normally have a shorter duration than subendocardial cells. This shorter duration
causes them to repolarize earlier than the longer action potentials found in the
subendocardium. This wave of repolarization travels away from the overlying recording
electrode and therefore displays a positive voltage. Subendocardial ischemia causes
subendocardial (Endo in figure) cells to have a shorter action potential duration and therefore
an earlier onset of repolarization. If this repolarization occurs prior to subepicardial
repolarization (see figure), then the wave of repolarization will travel towards recording
electrodes. This will result in an inverted T wave (dashed component of ECG tracing in figure).
Inverted T waves frequently occur during myocardial ischemic events.
Electrocardiogram ST segment changes
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 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).
ST segment depression can be observed when a patient with suspected coronary artery disease
undergoes an ECG stress test. While a 12-leaded ECG is recorded, the patient is asked to walk on
a treadmill and the work level is stepped up by increasing speed and incline to mimic exercise. If
the increase in coronary blood flow is insufficient for the increase in myocardial oxygen
demand, the myocardium becomes hypoxic, particularly in the ventricular subendocardium. The
patient may experience symptoms of exertional angina and at the same time display an
abnormal ECG. It is not uncommon to observed ST segment depression under these conditions.
Although ST depression cannot be localized within the heart like acute ST elevation or Q waves
of old myocardial infarctions, the ST depression is nevertheless indicative of acute myocardial
ischema and hypoxia.
ST segment depression occurs because when the ventricle is at rest and therefore repolarized,
the depolarized ischemic subendocardium generates electrical currents that are recorded by an
overlying electrode. If the depolarizing currents are traveling toward a positive recording
electrode, the baseline voltage prior to the QRS complex (which is normally isoelectric - i.e.,
zero mV) will be elevated (red line above zero prior to R wave in resting figure). In contrast,
when the ventricle becomes depolarized, all the muscle is depolarized so that zero voltage is
recorded by the electrode as usual. After repolarization, the voltage following the T wave (red
line after the T wave) remains positive as in the resting state. Therefore, the net effect of the
elevated baseline voltage is that the ST segment appears to be depressed relative to the
baseline.
Many patients undergoing a "heart attack" caused by complete thrombotic occlusion of a
coronary artery will show an elevation of the ST segment recorded by electrodes that overlie
the ischemic tissue. Because this event results from complete coronary occlusion, the ischemic
region and subsequent infarcted tissue spans the entire thickness of the muscle wall from
endocardium to epicardium (i.e., transmural ischemia). Other changes may also occur over
time, especially with the T wave (e.g., T wave inversion). To be diagnostic, ST segment elevation
must be at least one small square above the baseline and observed in two or more contiguous
leads in order to localize the ischemic injury. For example, ST elevation in leads II, III and aVF
indicate inferior wall ischemia, and ST elevation in leads V5 and V6 indicate left
ventricular anterolateral ischemia.
ST segment elevation occurs because when the ventricle is at rest and therefore repolarized, the
depolarized ischemic region generates electrical currents that are traveling away from the
recording electrode; therefore, the baseline voltage prior to the QRS complex is depressed (red
line before R wave). When the ventricle becomes depolarized, all the muscle is depolarized
during the ST segment so that zero voltage is recorded by the electrode (red line after R wave).
When the ventricle is completely repolarized after the T wave, the baseline is once again
negative as in the resting state. Therefore, the net effect of the depressed baseline voltage is
that the ST segment appears to be elevated relative to the baseline.