Cardiovascular Mechanics

Question 1

What is meant by excitation-contraction coupling?

Why is calcium important for the contraction of the heart, and how does cardiac and skeletal muscle differ in terms of calcium?

Answer 1

The series of events, from the production of an electrical impulse to the contraction of muscles in the heart

Calcium must be found outside the cardiac cell, which must then enter the cardiac cell to produce a contraction

Calcium is not required extracellularly for skeletal muscle (unlike for cardiac muscle)

Question 2

What is the single cell structure of a cardiac muscle cell?

Answer 2

Contains: T-tubules (transverse tubules), which are finger-like invaginations on the cell surface (folds that form small pouches), that coincide with each Z-line -

Myofilaments

Sarcoplasmic reticulum - lace-like structure that weaves / sits over the myofilaments

Many mitochondria

Question 3

What is the the function of the T-tubules?

What is the primary function of the sarcoplasmic reticulum?

Why do they contain many mitochondria?

Answer 3

Carry surface electrical signals deeper into the cell

Ca²⁺ storage - normally actively pumps in Ca²⁺

To provide the high demand of ATP for muscle contraction

Question 4

How does the structure relate to the calcium induced calcium release contraction? What are the steps of the calcium induced calcium released process?

What happens to the calcium during relaxation?

What is the Na⁺/ Ca²⁺ exhange system?

Answer 4

The T-tubules contain L-type Ca²⁺ channels that sense the arriving action potential, and so open

Ca²⁺ enters the cardiac cell, as there is a higher [Ca²⁺] outside than inside, so it moves down the concentration gradient

Ca²⁺ binds to the ryanodine receptor on the sarcoplasmic reticulum, causing a conformational change, which opens up the ryanodine receptor to allow Ca²⁺ out

The Ca²⁺ bind to the myofilaments to induce contraction

Ca²⁺ is pumped back into the sarcoplasmic reticulum using active transport

Na⁺ / Ca²⁺ exchange system is found on the T-tubules and maintains a low intracellular Ca²⁺ level during relaxation = steady balance (what comes in goes out), uses downhill energy gradient of Na⁺ to expel Ca²⁺from the cell

Question 5

How does skeletal muscle differ from cardiac muscle?

Answer 5

Has a mechanical link between the L-type Ca²⁺ channel to the ryanocide channel (therefore does not require extracellular calcium)

Question 6

What is the relationship between [Ca²⁺] in the cytoplasm and force production?

Answer 6

Sigmoidal relationship between Ca²⁺ in the cytoplasm and force production

As Ca²⁺ in the cytoplasm increases, the force produced by the muscle also increases as more myofilaments are activated

Question 7

How does the force produced by the cardiac muscle change according to the length-tension relation in cardiac muscle?

Answer 7

A stimulatory pulse excites a bundle of muscle fibres resulting in force production. When the same stimulatory pulse excites a bundle of muscle fibres that have been stretched / lengthened, a greater force is produced

Increasing the length of the cardiac muscle by applying tension increases the force produced by the cardiac muscle

Question 8

What is the length-tension relationship with force of the cardiac muscle?

How does active force production change?

Which type of force increases linearly?

Answer 8

Length-tension relationship with cardiac muscle shown on the graph:

Active force production = increases up to a certain point, then drops

Passive force (AKA baseline force also increases with length) = elastic component of the muscle also stretches, does not occur via myofilament interaction, it is part of the cytoskeletal component of cell stretching where there is no shortening of the muscle (isometric contraction)

Question 9

How does active and passive force production in relation to length and tension compare with skeletal muscle?

In the diagram, which part of the cardiac length-tension graph is relevant / important and why?

Answer 9

Active force in both, cardiac and skeletal muscle have a similar relationship with length of muscle

Cardiac = more resistant to stretch due to pericardial sac and extracellular matrix contents, and so less compliant than skeletal muscle

Skeletal muscle = similar pattern but less passive force formed = less resistant to stress

Cardiac = only the ascending limb of the graph is important as cardiac muscle physiologically only works on the ascending limb of the graph

Question 10

What is meant when a person says they have ‘pulled’ a muscle?

Is it possible to overstretch cardiac muscle?

Answer 10

Overstretching the skeletal muscle = thick and thin filaments are torn apart resulting in pain and inflammation

Cardiac tissue is not overstretched as it is contained in the pericardial sac (a membrane that surrounds the heart), which does not allow the heart to overstretch

Which is why under normal physiological conditions, the cardiac length-tension relationship is only relevant for the ascending limb

Question 11

What is the difference between isometric and isotonic force production?

How does this apply to the heart? Which of these apply to the heart?

Answer 11

Isometric = muscle fibres do not change length e.g. during the cardiac cycle, pressures increase in both ventricles

Isotonic = muscle fibres shorten in length e.g. during the cardiac cycle, blood is ejected from the ventricles

So the heart first produces isometric contraction, then isotonic contraction during its contractile cycle

Question 12

What is the preload?

What is the afterload?

What pattern does the preload (stretch) produce on force production?

How does the afterload affect shortening of the muscles?

Answer 12

Weight that stretches muscle before it is stimulated to contract

Weight not apparent to muscle in resting state, only encountered when the muscle has started to contract

Same as the length-tension theory, increase in preload (stretch) increases force production up to a certain point

The greater the afterload, the more isometric contraction rather than isotonic (so less shortening of the muscles)

Question 13

How does preload affect the contracting ability of the muscle?

How does afterload affect the contracting ability of the muscle?

How can the relationship between the afterload and shortening of muscle fibres be changed by altering the preload?

Answer 13

Greater preload allows for muscle fibres to produce more contraction

Greater afterload = reduced shortening of the muscle

For the same amount of afterload, more contraction is generated if the muscle has a greater preload (due to prestretching of the muscle)

Question 14

How does preload apply to the heart during contraction?

What is the preload in the heart?

What are 3 different measures of preloads in the heart?

Answer 14

As the blood fills the heart during diastole, it stretches the ventricular walls (acts as the preload)

Preload = depends on amount / volume of blood returning to the heart i.e. the volume of blood in the heart just before the heart contracts

Measures of preloads = end-diastolic volume, end diastolic pressure and right atrial pressure

Question 15

Why does the effects of the preload fit the function of the heart?

Answer 15

It is able to produce a contraction force that matches the volume of blood that is entering the heart

Small volume of blood returning = lesser stretch = lesser force production

Large volume of blood returning = greater stretch = greater force production

Question 16

How does afterload apply to the heart during contraction?

What happens to the muscle fibres if the afterload increases?

What is the reason then for keeping BP low, especially diastolic BP below 80 mmHg?

How does high BP affect the heart?

Answer 16

Afterload is the pressure against the ejection of blood from the left ventricle after the opening of the aortic valve (i.e. diastolic BP)

Any increase in afterload decreases the amount of isotonic contraction (shortening of the muscle fibres)

To decrease the afterload, as the diastolic BP is the pressure against which the heart has to work to eject the blood

High BP = higher afterload = heart needs to work harder

Question 17

What is the amount of preload and amount of afterload in the heart?

How does this translate onto the isometric and isotonic

Answer 17

Amount of preload = volume of ventricular filling

Amount of afterload = pressure in the aorta (affects when the aortic valve opens)

Question 18

What is the Frank-Starlling law / relationship?

What is consequence of this law in the heart?

Answer 18

As filling of the heart increases, the force of contraction also increases

Increased diastolic fibre length (i.e. increase in myocardial fibre length during diastole) = increased ventricular contraction

Consequence = results in a greater stroke volume, so that the cardiac output balances the greater venous return

Question 19

What could be the cause of the Frank-Starling relationship?

How can too much stretching affect skeletal muscle especially?

Answer 19

Changes in the number of myofilament crossbridges that interact - as the sarcomere length increases, better spacing between the thick and thin filaments

If there is less stretching, the actin filaments fold in on itself = fewer crossbridges formed

Pulling thick and thin filaments too far from each other (occurs esp. in skeletal muscle) - no contraction can be formed as no crossbridges can be formed between them

Question 20

What could be another cause of the Frank-Starling relationship?

How was this theory investigated in an experiment?

What is another theory for the Frank-Starling relationship?

Answer 20

Changes in the Ca2+ sensitivity of the myofilaments - at longer sarcomere lengths the troponin’s affinity to Ca²⁺ is increased due to conformational changes in protein

An experiment conducted had same [Ca²⁺] for all the different lengths / stretches of the muscle, and it was found that increased muscle length = increased force

Another experiment also found for stretched muscle, troponin’s affinity for Ca²⁺ increased as lesser [Ca²⁺] resulted in the same force production

2nd theory = with stretch, the space between the actin and myosin filaments decrease (known as decreasing myofilament lattice spacing), so the probability of forming strong binding crossbridges increases

Question 21

What is another property of cardiac structure in terms of stroke work?

What is the formula for stroke work?

What affects stroke volume and how?

What affects pressure and how?

Answer 21

Stroke work = work done by the heart to eject blood under pressure into the aorta and pulmonary artery

Stroke work = stroke volume (SV) x pressure (at which the blood is ejected)

Preload and afterload affect SV; e.g. greater afterload = smaller SV, greater preload = greater SV

Cardiac structure affects pressure; e.g. the tension in the walls, radius of the cyclinder, thickness of the walls etc. Apply the law of LaPlace

Question 22

What is the law of LaPlace?

What is the formula for the law of LaPlace?

Answer 22

When the pressure within a cylinder is held constant, the tension on its walls increases with increasing radius. Therefore, wall tension = pressure of the vessel x the radius of the vessel

Wall thickness all affects wall tension, so the overall formula is:

wall tension = pressure of the vessel x the radius of the vessel / the wall thickness

T = (PxR)/h

Question 23

How and why do the left and right ventricles differ?

Answer 23

The heart has musculature around the left and right ventricles, but the left ventricle produces a greater pressure than the right

It is due to the due to the geometry of the ventricles and the thickness of the ventricle walls

Right ventricle has a greater radius of curvature than in the left ventricle. Curvature determines the radius of the ventricle

So using the equation, T = (PxR)/h, a greater radius in the right ventricle results in the generation of a lesser pressure

As the right ventricle generates a less pressure than left ventricle, the wall thickness is smaller

Question 24

Using the law of LaPlace, T=(PxR)/h, how do e.g. the ventricles of a giraffe differ from the ventricles of a frog?

How does the heart change shape during heart failure?

Answer 24

Giraffe: has more narrow, long, thin ventricles = v. small radius, so for the same amount of force, a greater pressure can be achieved

Frog: Not much muscle, almost spherical in shape = larger radius so for the same amouont of force, a smaller pressure is achieved

Heart failure: the heart becomes dilated = greater radius, so the heart needs to work harder to produce a greater force in order to generate the same amount of pressure

Question 25

Arrange the sequence of events to produce a contraction:

Answer 25