Cardiac Force Generation

Question 1

What is the calcium induced calcium release mechanism

Answer 1

Upon depolarisation, voltage gated calcium channels open, which allows for the influx of calcium into the cell. This opens Ryanodine receptors on the sarcoplasmic reticulum which allows calcium to enter the cytoplasm from the SR

Question 2

What does the rise in intracellular calcium result in

Answer 2

In contraction of the sarcomere - occurs during systole

Question 3

What occurs when calcium re-enters the SR via SERCA2

Answer 3

The resulting drop in calcium levels results in muscle relaxation - occurs during diastole

Question 4

What motion is the left ventricle contracting in

Answer 4

In the left ventricle, contraction of circular muscles reduces the diameter of the ventricle from the apex towards the base. Because of the conical nature of the ventricle, this has the effect of squeezing the blood out of the ventricle, much like squeezing a tube of toothpaste. Secondly, the spiral muscles of the heart pull the mitral valve towards the apex, shortening the length of the heart, again acting to push blood towards the base

Question 5

What motion is the right ventricle contracting in

Answer 5

In the right ventricle, again spiral muscles pull the tricuspid valve towards the apex, shortening the length of the heart and pulling blood towards the base. Secondly, this has the effect of pulling the free wall of the heart towards the septum. Thirdly, the circular action of the left ventricle results in the septum bulging into the right ventricle

Question 6

What does inotropy mean

Answer 6

Relating to cardiac contractility

Question 7

What does chronotropy mean

Answer 7

Relating to heart rate

Question 8

What does pre-load mean

Answer 8

The force exerted on the heart wall at the end of diastole

Question 9

What is the frank-starling mechanism

Answer 9

The amount of force that the heart could generate during systolic contraction, and thus the stroke volume, was directly related to end diastolic volume

Question 10

Why does increasing diastolic volume result in increased systolic pressure

Answer 10

As volume increases during diastole, the force that is exerted on the muscle wall (pre-load) stretches the muscle cells

This increased stretching of the muscle cells increases the tension of the sarcomeres.

When relaxed, there is considerable overlap of the actin filaments. Because actin filaments are polarised, myosin heads must bind to their corresponding actin filament (they cannot simply bind to the nearest one, it has to be the one which would result in contraction). Because of this overlap, only a few myosin heads can bind to their respective actin filaments to cause contraction. Also, because the sarcomere is relatively short, there is little room to bring them closer together (i.e. for the sarcomere to contract). Therefore the force of contraction in this model would be very little

However as we stretch the muscle, the sarcomeres become stretched as well, reducing the amount of actin overlap and revealing more actin for the myosin heads to bind to

When there is no actin overlap and all myosin heads can engage, we have the capacity for full contraction of the muscle

Question 11

What happens if the heart over stretches

Answer 11

The length-tension relationship is not infinite however. In cardiac muscle, the increase in tension elicited through stretching reaches a maximum at around 2.4um. If the heart muscle is stretched any more than this, tension drops precipitously.

This is because with increased stretch, the actin/myosin filaments begin to be pulled away from each other and so cannot interact

Question 12

The relationship between actin and myosin is thought to only cause 20% of the increased tension resulting from the increased stretching, what else causes the tension to increase

Answer 12

Sensitivity of the sarcomere to calcium

At increased stretch, troponin-C (which binds calcium to induce myosin head binding) increases its sensitivity to calcium, owing to conformational changes in its structure. The increased binding of calcium leads to greater force of contraction

Question 13

What is afterload

Answer 13

The opposing force which acts against blood leaving the ventricle

Question 14

What is the end systolic volume and what affects it

Answer 14

The amount of blood left in the ventricle after contraction is the end systolic volume (ESV), which is directly related to the contractility of heart (how forceful the contraction was) and the afterload (the force acting against blood leaving the heart)

Question 15

What does afterload prevent

Answer 15

Full shortening of muscle

Question 16

What happens if the afterload is 1. Increased 2. Decreased

Answer 16

1. Increasing afterload (e.g. by increasing aortic blood pressure) means that blood is ejected into the aorta at higher pressures (because the pressure in the left ventricle has to be higher than the pressure in the aorta to overcome the force acting against the aortic valve). If the contractility (inotropy) of the heart is maintained, then this will result in a reduced stroke volume – because the same
   pressure exerted by the heart is pushing against a higher pressure acting against it
2. If afterload is decreased then blood leaves the ventricle at a lower pressure and the heart can more easily act against this pressure, therefore stroke volume increases

Question 17

How does increasing sympathetic activation affect the heart

Answer 17

Increases force of contraction (inotropy)

Question 18

How does digoxin work

Answer 18

treat heart failure with reduced ejection fraction act by increasing the inotropy of the heart, thus increasing its contractility to maintain SV