Cardiac Output - CVS TUTORIAL

Question 1

Define cardiac output. What are the values at rest and exercise, and what determines stroke volume?

Answer 1

Cardiac output is the volume of blood pumped out of the heart per minute (per ventricle).
At rest, it can be 5 l/min, and during exercise, it can rise to about 20 l/min.

Three main things affect the stroke volume:

• the energy of contraction of the left ventricle
• preload
• afterload

Question 2

Define Starling’s Law. How does Starling’s Law affect cardiac output? What is the importance of Starling’s Law?

Answer 2

Starling’s Law states that the energy of contraction of the cardiac muscle is relative to the stretch of the muscle fibre at rest.
This means that the greater the stretch of the ventricle in diastole (because of more blood entering), then the greater the energy of contraction. This increases the stroke volume achieved in systole, which increases the stroke volume.

Starling’s Law helps maintain a constant volume of blood in the body by maintaining the output of the right/left ventricle.

Question 3

What is the underlying molecular mechanism of Starling’s Law?

Answer 3

With an unstretched fibre, there is overlapping actin and myosin. This means that there is mechanical interference, so there is less cross-bridge formation available for contraction.
However, with a stretched fibre, there is less overlapping actin and myosin. This means that there is less mechanical interference, so there is more potential for more cross-bridge formation. There is also an increased sensitivity to Ca2+ ions.

Question 4

Define Laplace’s Law. What is the importance of Laplace’s Law in normal ejection and in heart failure?

Answer 4

Laplace’s Law describes factors that determine left ventricular wall stress, which is a major determinant of myocardial oxygen demand.

At rest, it opposes Starling’s Law. With increased preload, the vessel’s radius is increased, which increases afterload, which decreases the blood ejection from the heart.
In heart failure, the hearts chambers dilate, once again increasing the radius, which increases afterload, which decreases ejection.

Question 5

What is contractility/inotropy? How does the Ca2+ cycle in cardiac muscle cells explain changes in contractility? How does digoxin work?

Answer 5

Contractility is the strength of the heart’s contractions during systole.
An increased concentration of Ca2+ in the cytoplasm reacts with the troponin to allow more interactions between actin and myosin to take place.

Digoxin works by inhibiting the Na+/K+ pump, increasing the amount of intracellular Na+. This means that the Na+/Ca2+ exchanger, to remove the Na2+ from the cell, start bringing in more Ca2+. This means that the amount of intracellular Ca2+ increases. Thus, there is an increased uptake of Ca2+ into the sarcoplasmic reticulum, and there is more calcium-induced calcium release.

Question 6

How does the stimulation of the sympathetic nervous system affect the heart?

Answer 6

Noradrenaline binds to β1 adrenoreceptors on the heart. This is a G-protein coupled receptor, coupled to an αGs subunit. When activated, it ultimately increases the levels of PKA. These phosphorylate Ca2+ channels, increasing their activity. This causes a Ca2+ influx, which also causes calcium-induced calcium release, which increases contraction.
When sympathetic nerves are stimulated, the heart rate increases.