ST segment changes in ischaemia: Much more than you wanted to know

vivianimbriotis | Oct. 23, 2024, 12:55 p.m.

When we die, for many of us it will be coronary ischaemia that escorts us offstage. Sometimes it comes for us early, and a phalanx of soldiers armed with alteplase or paclitaxel-eluting stents can stave it off for a time.

Every time I look at an ECG, the first thing that I look for, the ur-ECG finding that strikes fear, is ST elevation. This is the marker of coronary ischaemia, failure of the blood vessels to supply a region of the heart muscle with precious oxygen. Ask any medical student and they will recite this for you – ST elevation means ischaemia.

Wait, why?

How do ECGs even work, anyway?

Normally a cardiomyocyte is sitting there with a negative membrane voltage – meaning that the INSIDE of the cell (in the cytosol near the cell membrane) has a NEGATIVE charge, while the extracellular fluid around the cell has a POSITIVE charge.

This state of affairs is maintained in large part by the sodium-potassium ATPase pump, which exports 3 Na ions in exchange for importing 2 K ions, decreasing overall charge at the expense of huge quantities of ATP.

During a myocardial action potential, sodium rapidly flows into the cell in phase zero, reversing the membrane voltage (the cytosol is POSITIVE and the ECF is now NEGATIVE). Then there is a delicate dance as calcium flows in while potassium flows out (phase 1 and 2). Then in phase three, the calcium flux stops, and potassium flows out unopposed, leading to repolarization.

Turn your mind now to the depolarization wavefront. Here depolarized cells are on the right, polarized cells on the left.

The above stolen from without shame from Alex Yartsev).

The intracellular fluid is relatively electrically isolated from the surface of the body, on account of all the lipid bi-layer in the way. The extracellular fluid (ECF) around these cells, on the other hand, is in electrical communication with the whole-body ECF and therefore the body surface, so focus on the charge in the ECF only.

The NEGATIVE charge in the depolarized region sits immediately next to the POSITIVE charge in the polarized region, creating a voltage between the two regions. Going FROM the negative region TO the positive region, we would measure a positive voltage (as it would require a positive amount of energy to move the unit charge from negative to positive).

From far away, the heart appears like a big electric dipole, with one negative point charge at the center of all the depolarized mass, and one positive point charge at the center of all the polarized mass. When a positive and negative charge as separated by a small distance, they are termed an electrical dipole, and produce a characteristic electrical field.

The “dipole vector” is a vector pointing from the negative charge to the positive one (i.e. from depolarized to polarized). As the heart de- and re-polarizes, the 3-dimentional dipole vector wanders around, pointing this way and then that way, dancing. Call it D for short.

What is the electrical potential (voltage) at a point somewhere about a dipole? Consider the unit vector pointing FROM the dipole TO that point and call that vector R. The electric potential at that point is proportional to the dot product of D and R, and it falls off with the square of the distance from the dipole (for a derivation, Feynman will do a better job than me, although you’ll need to go back and read his excellent discussion of vector calculus to follow along).

In rough terms we can think of each lead of the ECG as a vector pointing from the negative electrode (i.e. placed on the right arm for lead I) to the positive lead (the left arm for lead I), and the trace we see for that lead is the voltage for that vector. Since that voltage is proportional to the dot product of the lead’s vector and the heart’s dipole vector, the end result of this is that we see the a 2D PROJECTION of the 3D dipole vector, in the direction of the lead.

For example, lead I points from right to left. If the overall dipole vector points to the left, then lead I will be positive (regardless of whether the dipole vector is pointing up or down, anterior or posterior).

Similarly, aVF points down, so it is positive whenever the overall dipole vector points more down that up.

Note that the dipole approximation only works if you’re far enough away from the dipole, so in dilated cardiomyopathies and the like the ECG can no longer be thought of as a series of projections of a single, unified, time-varying 3D electrical dipole (and instead as the result of multiple smaller, regional dipoles).

If all of this has failed to cement the mechanism of the ECG in your mind, then I invite you to turn instead to a much better science communicator in the form of Alex Yartsev.

 

Ionic effects of myocardial ischaemia

When cells become ischaemic, they cannot make much ATP, which is what they needed that oxygen for in the first place. This means that the ATP-hungry N/K ATPase pump fails, with three consequences

-           Potassium leaks into the local ECF

-           Sodium leaks into the cell

-           The membrane voltage becomes less negative (The cytosol becomes LESS negative, the ECF becomes MORE negative).

In addition, there is a potassium channel that is closed in the presence of ATP and opens once ATP is scarse (K_ATP, this is the same channel that mediates insulin release in pancreatic beta cells, by the way). https://pubmed.ncbi.nlm.nih.gov/1310443/

Why on earth would you want such a channel? Well, it prevents ischaemic cell death. To see why, we must analyze how ischaemia changes the action potential.

Sodium influx is slowed, partly because there is more intracellular sodium, decreasing the concentration gradient; this slows conduction speed through ischaemic tissue and is arrhythmogenic as a result (there is more time for intraventricular/reentry circuits to form if the propagation speed is slower). As far as I can tell, this is not adaptive, just bad.

The potassium efflux during stages 1, 2, and 3 is augmented, because the voltage-gated K current is now augmented by the K_ATP leak, resulting in rapid repolarization and a shortened action potential. This results in decreased intracellular calcium, and therefore decreased contractility and energy consumption, preserving ATP for essential cellular processes to try to help more cells survive.

Consider now the effect of all of this on the ECF charge in the ischaemic region.

-           During polarization / stage 4, the ECF charge in ischaemic regions is MORE NEGATIVE than the rest of the heart, due to failure of ischaemic Na/K ATPase to maintain normal membrane potentials

-           During depolarization, the ECF charge in ischaemic regions is MORE POSITIVE than the rest of the heart (because it repolarizes much earlier, returning to a negative membrane voltage while the rest of the myocardium is still depolarized)

You can see this in action with an excellent computer simulation by Okada and collages, whose work I have cannibalized into this figure. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10717899/

 

 

How do these ionic effects result in ischaemic ST changes?

During the TP and PR interval, the heart is polarized. Due to the ionic leak in ischaemic tissue, there is a relative NEGATIVE charge there, so leads pointing through normal tissue to ischaemic tissue will see a negative voltage, leading to TP and PR depression. On its own this will result in ST elevation (by causing everything-but-ST depression).

During the ST segment, the heart has depolarized. Here the ischaemic tissue repolarizes early, resulting in a relative POSITIVE charge in the ischaemic ECF, augmenting ST elevation further.

This phenomenon explains other features of ischaemia on ECGs:

-           Ischaemia can be localized, because only leads pointing from non-ischaemic to ischaemic tissue will exhibit ST elevation

-           Leads pointing from ischaemic to non-ischemic tissue will see the opposite voltages, resulting in reciprocal depression

-           Since there are no posteriorly-facing leads, posterior infarcts will manifest only as ST depression in anteriorly-oriented leads

-           In global subendocardial ischaemia, all leads will see the subendocardial ischaemic tissue, then see the normal epicardial tissue, resulting in global ST depression

-           In regional subendocardial ischemia, leads pointing through the region of ischaemic subendocardium and then into normal tissue will exhibit ST depression.

How to summarize this awful obsession of mine?

The origin of ST elevation is mostly related to global ECG depression except during the ST segment, due to a regional extracellular negative charge accumulation.

Potassium efflux (through KATP, and Na/K pump failure) leads to early repolarization, and intracellular sodium leak decreases the magnitude of the Na gradient, leading to a less positive cell during the ST segment, further contributing to ST elevation.

Vectors that point from normal tissue to ischaemic tissue will see ST elevation, visa versa ST depression. This is why subendothelial ischaemia causes ST depression, as do posterior STEMIs.

This is a useful mental model, but the dipole approximation of the ECG holds best when the electrodes are far away from the heart, and so becomes less accurate in cardiomegaly.