Cardiac contractility

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Cardiac contractility

Cardiovascular system


Cardiac contractility

USMLE® Step 1 questions

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High Yield Notes

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USMLE® Step 1 style questions USMLE

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A patient participating in a clinical trial takes a new drug that increases cardiac contractility. The patient’s left ventricular ejection fraction increases from 55% to 65% after taking the medication. Via which of the following mechanisms does this new drug most likely work?  


The main job of the heart is to pump blood all over the body, to our organs and tissues and keep them oxygenated.

It does so by contracting around 70 times per minute.

The physiological basis of cardiac contractility is the synchronous contraction of heart muscle cells, aka cardiomyocytes.

Cardiac contractility is a measure of the strength of cardiomyocytes, to contract.

In order for cardiomyocytes to contract, they first need to depolarize.

Depolarization is when ions move across the membrane of a cell, and the membrane potential becomes less negative or even slightly positive.

Think of a really pessimistic negative cell throwing his hands up and enjoying a moment of joy.

When one cell depolarizes enough - it can cause some ions like calcium to flow into neighboring cells and trigger them to depolarize as well.

If one cell after another depolarizes, then there’s a depolarization wave which you can imagine would look like a wave moving through a crowd at a football stadium.

Each depolarization wave causes a heart muscle contraction, so the rate at which depolarization waves ripple through the heart actually sets the heart rate.

This depolarization wave starts with the sinoatrial node, which sometimes gets called the SA node and then moves through the rest of the heart to cause a contraction.

So if depolarization waves are going through about once per second, that means that your heart beats once per second, or sixty times in a minute.

Now let’s zoom in on a cardiomyocyte.

These hard working cells have branches and intercalated disks along their edges which have small holes called gap junctions that allow ions to flow from one cardiomyocyte to the next.

When ions like calcium move from that cell into a neighboring cell, this triggers depolarization, and cardiomyocytes depolarize one after another.

Another feature of cardiomyocytes are passageways called transverse tubules, or T-tubules.


Contractility is the ability of the heart muscle to contract and thereby pump blood. Cardiac contractility is determined by the interaction between intracellular calcium concentration, and the myofilament cross-bridge cycling. The Frank-Starling mechanism is a key factor in determining cardiac contractility. This mechanism states that the more stretched (tensed) a heart muscle fiber is, the more calcium it will release from its stores, leading to increased contraction force.


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  4. "Principles of Anatomy and Physiology" Wiley (2014)
  5. "Effects of cardiac contractility modulation by non-excitatory electrical stimulation on exercise capacity and quality of life: An individual patient's data meta-analysis of randomized controlled trials" International Journal of Cardiology (2014)
  6. "Clinical effects of cardiac contractility modulation (CCM) as a treatment for chronic heart failure" European Journal of Heart Failure (2012)
  7. "Impact of Cardiac Contractility Modulation on Left Ventricular Global and Regional Function and Remodeling" JACC: Cardiovascular Imaging (2009)

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