cardiac mechanics

Question 1

• What does a ventricular cell require for contraction?

- Outline the basic process leading up to the contraction of a ventricular cell

Answer 1

Calcium and excitation of cell.

    Electrical event (AP) 
    Calcium transient (amount of calcium in sarcoplasm has ^ for short period of time). 
    Contractile event

Question 2

• Can the hearts contractility be sustained by saline solution with bicarbonate of soda and potassium chloride?
• Does skeletal muscle need external calcium for contraction?

Answer 2

No; the addition of lime or a calcium salt will restore good contractility.

no

Question 3

• What component of a ventricular cell takes up the largest volume?
• What are the other percentages for the components of a ventricular cell?

Answer 3

Myofibrils (46%)

mitochondria (36%), sarcoplasmic reticulum (4%) nucleus (2%) other (12%)

Question 4

• What are T-tubules?

- Outline the dimensions of a ventricular cells (i.e. length, width etc.)

Answer 4

Finger-like invaginations of the cell surface.

Ventricular cell length is 100micrometers and width is 15micrometers. 
T-tubule 200nm in diameter. T-tubules are separated by 2micrometers, intermediate between each Z-line of myofibril, transmitting surface depolarisation deep into the cell

Question 5

• Explain the process of excitation-contraction coupling (first three steps)

Answer 5

1. L-type Ca2+ channel, upon excitation, the depolarisation is sensed by the ion channel in the cardiomyocyte, consequently this opens the channel in response to AP.
   
   2. Extracellular Ca2+ moves across concentration gradient intracellularly by diffusion.
   3. Minor proportion of Ca2+ activates actin filaments and directly causes contraction.

Question 6

Explain the process of excitation-contraction coupling ( steps 4,5 6)

Answer 6

4. Majority of Ca2+ binds to RyR (ryanodine receptors) on SR (SR Ca2+ release channel); receptor undergoes conformational change (Ligand gated); opening RyR (aka SR calcium release channel) → Enables from SR.
   
   5. Ca2+ binds to Troponin C on actin filaments to stimulate shortening of sarcomere (sliding filament theory)
   6. Relaxation period: Ca2+ actively pumped into a stored position by Ca2+ ATPase channels of SR. Same amount of Ca2+ that came into the cell is effluxed by a Na-Ca exchange.

Question 7

Sketch a graph of the relationship between force production and intracellular signalling and then explain it

Answer 7

Sigmoidal graph

Explanation: Force-Ca2+ relationship sigmoidal. Intracellular cytoplasmic Ca2+ ^ will subsequently result in a greater force exerted by the muscle. (10 micromoles intracellular concentration sufficient to produce maximum force.)

Question 8

• Explain the length-tension relation (LTR) in cardiac muscle
• What are active and passive force?

Answer 8

As we increase length the active force produced also increases provided we stimulate the cardiac muscle

Active - Dependent on sarcomere shortening, forces act in the direction of point of muscular attachment towards centre.
Passive - Based on the resistance to stretch of the muscle

Question 9

• What is the total force?

- Which type of muscle is more resistant to stretch and less compliant and why?

Answer 9

Passive force + Active force

Cardiac muscle because of the properties of its extracellular matrix and cytoskeleton.

Question 10

• Which limb (ascending or descending) for cardiac muscle is important for the LTR?
• What is isometric and isotonic contraction?

Answer 10

only ascending

Isometric - Sarcomeres and muscle fibres don't change length, but pressures increase in both ventricles. 

E.g. plank

Isotonic - Shortening of fibres and blood is ejected from ventricles. 

E.g. Bicep curls, bench press etc.

Question 11

• Define preload

- Define afterload

Answer 11

Degree to which cardiac muscle cells are stretched from filling of the ventricles prior to contraction

Refers to tension/force that ventricle must develop to pump blood effectively against the resistance in the vascular system

Question 12

• What does increased preload do to contractility?
• What is preload dependent on?
• What do measures in preload involve?

Answer 12

Increased preload → Increased stretching → Increased force therefore increased contractility.

Venous return 

End-diastolic volume (EDV) 
End-diastolic pressure (EDP) 
Right atrial pressure

Question 13

• What effect does increased afterload have on isotonic contraction?
• What do measures in afterload involve?

Answer 13

Increased afterload leads to decreased amount of isotonic shortening and decreases the velocity of shortening.

Diastolic blood pressure

Question 14

• Define the Frank-Starling relationship and what the consequence is

Answer 14

Definition - Increased diastolic fibre length increases ventricular contraction

Consequence - Ventricles pump greater stroke volume so that, at equilibrium, cardiac output exactly balances the augmented venous return

**Diastolic fibre length^ → Ventricular stretching^ → Greater SV → Increased cardiac output
(So if we get more venous return we get more stretch on ventricular muscle therefore producing a more powerful contraction)

Question 15

What are the 2 factors that are thought to cause the Frank-Starling relationship and then explain each one?

• Changes in the number of myofilament cross-bridges that interact

Answer 15

Ventricular stretching subsequently increases contact between the myosin heads with the myosin binding sites presented by the thin actin filaments,

as actin filaments don’t overlap on themselves as much

Question 16

Explain factors that affect frank starling relationship

• Changes in calcium sensitivity of the myofilaments (first hypothesis- conformational change )

Answer 16

Ca2+ required for myofilament activation, troponin C (Troponin C), is thin filament protein that binds Ca2+, subsequently causing tropomyosin to expose myosin binding sites, regulating formation of cross-bridges between actin and myosin.

At longer sarcomere lengths, the affinity of Troponin C for Ca2+ is increased due to conformational change in protein; thereby less Ca2+ is required for equivalent amount of force.

Question 17

• What is stroke work (include equation)?

- What 3 primary factors affect stroke work?

Answer 17

Work done by heart to eject blood under pressure into aorta and pulmonary artery.
Stroke work = SV x pressure at which blood is ejected

Preload, contractility and afterload.

Question 18

• Define the Law of Laplace.

Answer 18

When the pressure within a cylinder is held constant, the tension on its wall increases with increasing radius.

Wall tension = Pressure in vessel x Radius of vessel 

T = P x R 

(Incorporating wall thickness: T = (P x R)/h)

Question 19

Explain factors that affect frank starling relationship

• Changes in calcium sensitivity of the myofilaments (2nd hypothesis- lattice spacing )

Answer 19

lattice-spacing decreases as myofibrils are stretched

Decreasing myofilament lattice spacing, increasing the probability of forming strong-binding-cross-bridges; providing more force for the same amount of activating calcium

Question 20

• Which ventricle of the heart generates greater pressure and why?

Answer 20

Radius of curvature of walls of left ventricle lower than that of right ventricle hence it can generate higher pressures with similar stress.

LV: Lower R therefore greater P; T is constant.

Question 21

• What happens to the structure a failing heart?

Answer 21

Becomes dilated and spherical which increases wall stress