L25 – Control of the Heart

Question 1

How is cardiac output calculated?

Answer 1

Stroke volume x Heart rate = cardiac output

Question 2

Modify which two parameters can change cardiac output?

Answer 2

Stroke volume

Heart rate

Question 3

What is the one parameter that must increase for cardiac output to increase? Why?

Answer 3

Venous return must also increase

Because heart is closed system, can only output the input

Question 4

What is stroke volume a function of?

Answer 4

Filling and force of contraction

Question 5

How does contractility and rate of force development related?

Answer 5

rate of force development =contractility

Question 6

What are the 2 ways that the force of contraction can be increased?

Answer 6

1) Prolong time of contraction at same rate of force development
2) Increase rate of force development but keeping same time of contraction

Question 7

What ion does contractility depend on?

Answer 7

Intracellular Ca2+ concentration (relating to number of actin- myosin crossbridges formed)

Question 8

Total force of contraction of ventricles is influenced by intracellular Ca2+ concentration, how?

Answer 8

Increase intracellular Ca2+ conc. > more excitation-contraction coupling > Increase number of actin-myosin crossbridges form > Increase force of contraction

Question 9

What are the two mechanisms for controlling Force of Contraction in heart?

Answer 9

Homeometric

Heterometric

Question 10

What is the difference between homeometric and heterometric control of force of contraction in heart ventricles?

Answer 10

Homeometric = change in rate of force development, no change in muscle length, same duration of contraction

Heterometric = change in muscle length, same rate of force development, prolong duration of contraction

Question 11

What causes change in ventricular muscle length (heterometric control)?

Answer 11

When ventricle walls are more stretched

e.g. increase venous return fills and stretches ventricular wall

Question 12

What is the main role of heterometric control of contractility?

Answer 12

Protective, prevent overfilling

Question 13

Which of 2 controls of contractility is intrinsic, which is extrinsic?

Answer 13

Heterometric always INtrinsic - arise from within muscle itself/ autoregulation

Homeometric= INtrinsic OR EXtrinsic - induce by external agent on ventricular muscle

Question 14

Which mechanism is autoregulatory of venous return volume?

Answer 14

Heterometric control (intrinsic)

Question 15

Heterometric control changes contractility or not?

Answer 15

No, doesnt change rate of force development

Only prolongs duration of contraction

Question 16

Does homeometric control change contractility or not?

Answer 16

Yes- Change rate of force development

Same duration of contraction

Question 17

What do inotrophic and chronotropic refer to ?

Answer 17

Inotrophic = change in contractility 
Chronotrophic = change in HR

Question 18

Explain Inotrophic mechanism/cardiac excitation-contraction coupling, starting with cardiac AP, channels, ion movements… to contraction.

Answer 18

Cardiac AP > Open L-type channels in cell membrane and T-tubule during plateau of AP > Entry of extracellular Ca2+ through Ryanodine receptor by diffusion

> Induce Ca2+ release from sarcoplasmic reticulum > Ca2+ diffuses to contractile protein > Bind to troponin to expose tropomyosin for actin binding/ crossbridge > contraction

Question 19

Explain how Ca2+ moves out of cardiac cell in diastole.

Answer 19

Removal of AP > Uptake of Ca2+ back to SR by Sarcoplasmic Reticulum Ca-ATPase (SERCA) > detach cross bridge > Ca2+ pumped from SR to extracellular space

Question 20

Why is it necessary that Ca2+ exits cardiac cell in diastole?

Answer 20

Balances initial Ca2+ entry in AP

Question 21

What is the main channel used to pump Ca2+ to extracellular space during diastole apart from SERCA?

Answer 21

Ca2+ movement mostly by Na/Ca exchanger

Na+ moves down through concentration gradient

Question 22

How does inotropic mechanism depend on Ca2+ conc. intracellular?

Answer 22

Increased intracellular Ca = increased Ca in SR
More Ca released from SR for excitation- contraction coupling
Increase no. of actin-myosin cross bridges form
Increases force of contraction

Question 23

How is homeometric mechanism different from sympathetic nerve control on force of contraction?

Answer 23

Homeometric = Increase rate of force development but NO CHANGE in duration of contraction

Whereas Sympathetic nerve DECREASES the time of contraction

Not the same***

Question 24

How is cAMP important to the sympathetic nerve control of contractility of ventricles?

(think what causes release of cAMP, what channels, receptors and proteins are involved)

Answer 24

Sympathetic nerve release noradrenaline > bind to B1-receptor on ventricular cell membrane

> activate adenyl cyclase > convert intracellular ATP to cAMP > cAMP activates Protein Kinase A > Phosporylate Ca2+ channel in cell membrane

> Increased time in open-state > increased calcium permeability during AP plateau > increase extracellular Ca2+ enter cell > increase contractility

Question 25

What channels does Protein Kinase A phosphorylate after being activated by cAMP?

Answer 25

SERCA and L-type Ca2+ channels in cell membrane

Question 26

Sympathetic control of contractility is different from homeometric control because it decreases duration of contraction. How?

Answer 26

Increased rate of Ca uptake into SR because of Protein Kinase A phosphrylating SERCA > more Ca pump from SR to extracellular space during diastole allows faster relaxation, shortening overall duration of contraction

Question 27

Sympathetic nerves also produces a minor effect in addition to changing contractility and duration. What is it?

Answer 27

Rate-induced regulation called Treppe effect | Increase in HR causes increase in Force of contraction

Question 28

Explain Treppe effect as a result of sympathetic nerve control of contractility.

Answer 28

Minor effect of raising HR > less time for diastole > less time for Ca to be pumped from SR to extracellular space > more intracellular Ca > increase force of contraction

Question 29

Does sympathetic or parasympathetic DIRECTLY affect heart contractility?

Answer 29

ONLY sympathetic can DIRECTLY affect contractility Parasympathetic can INdirectly affect

Question 30

How can parasympathetic innervation indirectly change contractility?

Answer 30

Vagus only innervates atria and nodal tissues (not ventricles) > cannot influence force but can change heart rate > change force indirectly by rate-induced regulation, Treppe effect

Question 31

What does heterometric autoregulation of heart/ Starling's law of the heart concern?

Answer 31

Effect of venous return on force of contraction of the ventricles

Question 32

How does venous return and contraction of ventricles relate?

Answer 32

Increase venous return = increase preload = increase ventricle filling = increase force of contraction (same contractility/ rate of force development)

Question 33

What two parameters can cause force of contraction to increase whilst keeping same contractility?

Answer 33

Increase venous return/ preload | Increase arterial pressure/ afterload

Question 34

How can increase in afterload increase force of contraction but maintain same contractility?

Answer 34

Increase arterial pressure/ afterload > Increase pressure to pump against (higher peripheral resistance > initial drop in stroke volume > increase end-systolic/ residue volume > increase end-diastolic volume > Increase force of contraction

Question 35

Why is there an optimum length to striated muscle? Remember that force of contraction depends on number of crossbridges formed.

Answer 35

Too long= reduce actin-myosin overlap Too short = distort filaments, reduce actin- myosin overlap Optimum = maximum actin- myosin overlap

Question 36

What length is cardiac muscle usually at in relation to its optimum length? Why?

Answer 36

Slightly shorter than optimum length Any stretching of cardiac muscle > closer to optimum length > more crossbridges form > Increase force

Question 37

How is congestive heart failure a result of cardiac muscle fiber property?

Answer 37

Overstretch of cardiac muscle > stretch beyond optimum length > reduce actin- myosin overlap > less force generated > cannot pump out over-filled ventricles > congestive heart failure

Question 38

Optimum length of muscle and its mechanism is related to which control mechanism?

Answer 38

Heterometric- since there is change in muscle length

Question 39

What is Cardiac function curve a graphical representation of?

Answer 39

graphical representation of cardiac force of contraction against length of ventricular muscle for the intact heart

Question 40

What can the cardiac function curve have on its x -axis? (3)

Answer 40

1) Ventricular muscle fiber length Since length increases with pressure and volume: 2) Left ventricular end-diastolic volume/ pressure 3) Right atrial pressure (indirectly measure ventricular muscle fibre length) (common)

Question 41

What can the cardiac function curve have on its y-axis? (4)

Answer 41

1) Force of contraction 2) Stroke work 2) Stroke volume 3) Cardiac output (proportional to force) (common)

Question 42

How can right atrial pressure be measured to produce cardiac function curve?

Answer 42

Right heart catheterization

Question 43

How does homeometric increase in force compare to heterometric increase in force on cardiac function graph?

Answer 43

Homeometric has steeper and higher curve

Question 44

Why does homeometric increase in force have higher and steeper curve in cardiac function graph? (remember properties of homeometric - extrinsic or intrinsic, and no filling)

Answer 44

Homeometric = same duration of contraction, increase rate of force development/ contractility, no change in muscle length Increase intracellular Ca2+ > change contractility > change slope of cardiac function curve (steeper, higher) > increase force

Question 45

Explain heterometric increase in force on cardiac function graph. (Heteormetric is always intrinsic)

Answer 45

Not higher and steeper curve like homeometric Increase muscle length due to more filling > reach optimal muscle length > increase force of contraction

Question 46

How does the heterometric and homeometric curve compare to normal ?

Answer 46

Heterotrometric : Position of cardiac function curve does not change, but shifted to the right due to higher right atrial pressure, same cardiac output Homeometric: same right atrial pressure associated with DIFFERENT cardiac output, steeper and higher curve than normal due to increased contractility

Question 47

Why do both homeometric and heterometric curves dip at high muscle length on the cardiac function graph?

Answer 47

Over-stretch = reduce actin-myosin overlap = reduce cross bridge formation = decrease force

Question 48

What heart structure resists overstretching of heart to prevent congestive heart failure?

Answer 48

Tough Fibrous pericardium is indistendable

Question 49

What is the position of the cardiac function curve for a congestive heart failure patient vs normal?

Answer 49

Curve shift to right, higher right atrial pressure

Question 50

What happens to cardiac function curve if patient has poor contractility e.g. ischaemic scar tissue?

Answer 50

Curve slope becomes shallower

Question 51

What pathological conditions can likely lead to congestive heart failure?

Answer 51

Heart unable to compensate heart failure by enabling heterometric effect and increasing force of contraction In hearts with poor contractility e.g. ischaemic scar tissue from MI

Question 52

What is the difference between compensated heart failure and decompensated?

Answer 52

Compensated = kick in heterometric effect, stretching > operate at maximal force to maintain normal stroke volume (a function of force and filling) Decompensated means over-stretching beyond optimum length and cannot recover, right atrial pressure at peak, heart gives up, congestive heart failure