Why does isoprotenerol potentially cause arrhythmia as a side effect?

[studylol]

What I know: Increased beta receptor stimulation = increased heart rate, increased isotropicity = increased O2 demand by heart.

So it sounds like it's inching towards ischemia, but not exactly there yet, else we would get an MI/angina. Do we know the mechanism of why increased O2 demand by the heart causes arrhythmia?

Thanks a lot!

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[usmleswot]

What I know: Increased beta receptor stimulation = increased heart rate, increased isotropicity = increased O2 demand by heart.

So it sounds like it's inching towards ischemia, but not exactly there yet, else we would get an MI/angina. Do we know the mechanism of why increased O2 demand by the heart causes arrhythmia?

Thanks a lot!

I'm not sure but I think it's because sympathetic stimulation increases cardiac excitation-contraction coupling and so can also trigger ventricular arrhythmias caused by afterdepolarizations.

Wiki:
Afterdepolarizations are abnormal depolarizations of cardiac myocytes that interrupt phase 2, phase 3, or phase 4 of the cardiac action potential in the electrical conduction system of the heart. Afterdepolarizations may lead to cardiac arrhythmias.

 

[studylol]

Interesting i've never heard of the term afterdepolarization. I appreciate your response, thanks.

So by some unknown mechanism probably linked to cardiac excitation and ischemia, there is a higher likelihood of afterdepolarizations. These interrupt the normal action potential and may cause arrhythmia. Did I summarize that accurately?

 

[usmleswot]

You're welcome Almost, I think it's more to do with previously sub-threshold impulses reaching threshold. Afterdepolarizations are produced by the preceding action potential (freak electrical activity in the aftermath of a large impulse so to speak) and so if you increase the amplitude of the cardiac action potential, I'm assuming that it triggers these impulses as well, to produce contraction and thereby arrhythmias.

 

[worldbeater]

I am not sure, but I would logic it out that it would go in a different direction.

It's a nonselective beta agonist, meaning it affects both beta1 receptors and beta 2 receptors. Beta 1 receptors cause constriction, while beta 2 receptors causes vasodilation. The constant yo-yo effect could lead the ventricle having problems an increased sodium influx into the cell (leading to a ventricular arrhythmia) or calcium influx into the atrium (leading to an atrial arrhythmia).

 

[shreypete]

If I recall correctly, afterdepolarization was one of the options mentioned on UW for a digoxin based q. Apparently digoxin can also cause afterdepolarizations.