Cardiovascular Mechanics

Question 1

How is the ventricular cardiomyocyte structured?

Answer 1

T- tubules are finger-like invaginations on cell surface
T tubules are spaced ~2microM so that every T tubule lies along a Z line of every myofibril
Sarcoplasmic reticulum surrounds every T tubule
Within T tubules are LTCCs- L type calcium channels- found close to ryanodine receptors
T -tubules carry depolarisations deep into cell

Question 2

What causes contraction in a ventricular cell?

Answer 2

During an electrical event there is a Ca2+ influx ad release of Ca2+ which leads to contractile event
The increase in Ca2+ conc. across a whole cell is known as Ca2+ transient

Question 3

What is the action of calcium?

Answer 3

1. Excitation at surface (of cardiomyocyte) causes depolarisation to be carried deep inside cell
2. Depolarisation is sensed by LTCCs- these change shape of the channel and allow Ca2+ in
3. Ca2+ binds to SR Ca2+ release channel (ryanodine receptor) causing it to open- allows Ca2+ to be released from SR into cytosol
4. Ca2+ binds to troponin in myofilament and causes contraction
5. For relaxation Ca2+ is pumped into SR by SR-calcium-ATPase
6. Same amount of Ca2+ that enters cell needs to be effluxed- its removed by sodium-calcium exchange system (uses energy gradient of Na)

Question 4

What is preload?

Answer 4

Degree of stretch at the end of ventricular filling in diastole

Question 5

What is afterload?

Answer 5

The pressure against which the heart ejects blood during systole

Question 6

What happens as we increase preload and afterload?

Answer 6

As we increase preload we increase force

As we increase afterload, amount of shortening is decreased (we want more shortening ideally)

Question 7

What occurs in preload?

Answer 7

Blood fills during diastole and stretches ventricular walls
This stretch determines preload on ventricles
Preload is depended on venous return
Measures of preload include end diastolic volume, end diastolic pressure, right atrial pressure

Question 8

What occurs in afterload?

Answer 8

Afterload is the load which the left ventricle has to overcome to eject blood after opening the aortic valve
Any increase in afterload decreases the amount of isotonic contraction and velocity of shortening
Measures of afterload is diastolic blood pressure

Question 9

What are the 2 types of muscle contraction?

Answer 9

Isotonic- shortening of muscle fibre to allow blood ejection

Isometric- no shortening of muscle fibre but pressure increases in ventricles as they fill

Question 10

What is the length-tension relationship?

Answer 10

Focuses on isometric contraction
Longer the muscle, greater the force produced by the muscle- this is formed by cross bridge formation in response to Ca2+ release from SR:
- Decreased sarcomere length means less preload and less stretch potential so less tension and less actin-myosin cross bridges so lower contraction potential
- Increase in preload leads to increase in active tension

Question 11

How does cardiac muscle compare to skeletal muscle?

Answer 11

1. Skeletal muscle is more stretchy whereas cardiac muscle is more resistant to stretch and is less complaint- this is due to properties of the ECM and cytoskeleton
2. For cardiac muscle, only the ascending limb is important for length-tension relationship
3. You can’t overstretch cardiac muscle but you can overstretch skeletal muscle (tear of myofibrils or pulled muscle)

Question 12

What is the frank-starling relationship?

Answer 12

Increase in diastolic fibre length increases ventricular contraction
With a large diastolic fibre length, ventricles pump a greater stroke volume- at equilibrium, cardiac output equals venous return

Question 13

What are explanations for frank-starling law?

Answer 13

1. change in no. of cross bridges formed:
   - Too much overall = very few cross bridges (Actin filament overlap)
   - Too little overlap = very few corss bridges
   - Optimum overlap = maximal cross bridges
2. Change in sensitivity of troponin-c to Ca2+
   - Troponin-C (TnC) regulates formation of cross-bridges between actin and myosin
   - Longer the sarcomere, the greater the affinity of Ca2+ by TnC due to conformational change in TnC
3. Change in lattice spacing
   - With stretch, space between actin and myosin decreases (lattice spacing decreases)
   - Smaller the lattice spacing the greater the probability of cross bridges to form between actin and myosin

Question 14

What is stroke work?

Answer 14

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

Question 15

What is the calculation for stroke work?

Answer 15

Volume of blood ejected with each stroke x pressure at which blood is ejected

Stroke work = SV X P

Question 16

What factors affect pressure?

Answer 16

Cardiomyopathy (thickening of heart walls)

Dilation of myocytes

Question 17

What factors affect stroke volume?

Answer 17

Contractility
Preload
Afterload

Question 18

What’s the Law of LaPlace?

Answer 18

When pressure within a wall is kept constant, tension in the walls will increase with increasing radius
This can be represents by T= P x r
However we need to account for wall thickness so we get:

T (Pa) = Pr/h
Where h = wall thickness is m
radius in m

Question 19

How is wall tension balanced across the heart?

Answer 19

Wall tension in right and left ventricles needs to be the same however they have different pressures
To ensure a balanced wall tension ventricles have different radii:
- radius of curvature of Lv is less than radius of Rv to generate the same stress in both
- Failing hearts become dilated which increases wall tension