Cardiac contractility and the events of the cardiac cycle

Question 1

Describe the molecular level of a cardiac muscle contraction.

Answer 1

1. Voltage gated Ca channels (L-type DHPR) sense change in membrane potential in T tubule and undergo conformational change 2. ~10% of the Ca2+ required for contraction enters from the outside though DHPR in the transverse tubular membrane 3. Calcium binds to RYR, opens it, and Ca2+ flows out (75% of Calcium required to trigger contraction) of the SR down its concentration gradient into the cytoplasm
2. Release of Calcium activates troponin C. This takes tropomyosin away from the myosin binding sites on actin, enabling strong actin-myosin binding

Question 2

Describe the molecular level of a cardiac muscle relaxation.

Answer 2

Requires a decrease in cytoplasmic Ca2+ concentration
-Ca2+ ATPase in sarcoplasmic reticulum is activated, pumping out some Calcium into the SR. Calsequestrin helps, given that calcium is transported against its concentration gradient (so that no free calcium, allowing calcium to get into the stores). -Some Calcium also transported out of the cell through Na+:Ca2+ exchange in the sarcolemmal membrane (3 Na+ in :1 Ca+2 out) -To prevent Sodium generating an AP, pumps sodiums out and potassium in

Question 3

What is the difference in the diameter and volume of T tubules between those of skeletal and those of cardiac muscle ?

Answer 3

Cardiac muscle T-tubules 5x greater in diameter than sk. muscle (25x more volume)

Question 4

Is Dihydropyridine to Ryanodine receptor linkage mechanical (such as is the case in sk. muscle) ?

Answer 4

No

Question 5

Distinguish between cardiac and skeletal muscle with regards to whether they can achieve different forces of contraction ? Explain this difference on a molecular level.

Answer 5

Sk: All or nothing
Cardiac: More Calcium released from sarcoplasmic reticulum, higher force of contraction generated

In skeletal muscle, 4 molecules of Calcium must bind to troponin in order for a contraction to take place. In cardiac muscle, troponin can accept less calcium (but this will result in a contraction which is not as strong as it can produce)

Question 6

What is the effect of resting heart rate on force of contraction ?

Answer 6

At resting heart rates, ↑[Ca2+]i due to influx and sarcoplasmic release is insufficient to cause maximal contractile force.

Question 7

Describe sympathetic innervation effect on cardiac muscle. Specifically, discuss the effects on Noradrenaline on cardiac muscle.

Answer 7

Overall positive inotropic effect (force of contraction) and increased heart rate.

Noradrenaline acts on β1 receptors:
– ↑[cAMP]i
– Enhances Ca2+ influx
– Promotes storage and release of Ca2+ from sarcoplasmic stores

This all results in ↑contractility (because higher amount of calcium in sarcoplasmic reticulum reticulum ) and ↑speed of relaxation

Question 8

Describe how widespread in the heart the effects of the SNS and PSNS are respectively.

Answer 8

SNS: Throughout entire heart
PSNS: Mostly to SA Node (innervates atria)

Question 9

Describe parasympathetic innervation effect on cardiac muscle

Answer 9

Indirect negative ionotropic effect (if you slow heart down, more time for Calcium to be pushed out into extracellular environment) but mainly just decreases heart rate

Question 10

Graph a function of cardiac tension over time with sympathetic innervation, no innervation, and parasympathetic innervation. Explain the shapes of the different graphs.

Answer 10

Refer to slide 6 of lecture on “Cardiac contractility and the events of the cardiac cycle”.
SNS innervation increases force you can generate (increased contractility), and causes quicker relaxation (increased speed of relaxation)
PSNS innervation decreases force you can generate.

Question 11

Rank sympathetic innervation, no innervation and PSNS innervation in increasing ionotropic state.

Answer 11

SNS > No innervation > PSNS

Question 12

Why is it impossible to summate cardiac muscle contractions (tetanize cardiac muscle cells) ?

Answer 12

Because of refractory period

Question 13

Define absolute refractory period, and relative refractory period. Why do they occur ?

Answer 13

ABSOLUTE REFRACTORY PERIOD: “another stimulus given to the neuron (no matter how strong) will not lead to a second action potential.” Because “fast sodium channels are inactivated and therefore cannot reopen to normal depolarizing stimuli”

RELATIVE REFRACTORY PERIOD: “a stronger than normal stimulus is needed in order to elicit an action potential.” Some Sodium and Calcium become activated and ready to be opened.

Question 14

Define supranormal excitability.

Answer 14

Majority of voltage gated Sodium channels have reset (ready to open again) and it just takes a lower than normal signal to cause that to occur

Question 15

How long is the period of contraction, and the refractory period in skeletal muscle ?

Answer 15

– Absolute refractory period 1-2ms

– Period of contraction 20-100ms

Question 16

How long is the period of contraction, and the absolute refractory period in cardiac muscle ?

Answer 16

– Absolute refractory period (ARP) ~245ms

– Period of contraction 250ms

Question 17

Draw a graph of an AP in cardiac muscle, clearly showing the ARP, RRP, and SNP.

Answer 17

Refer to slide 7 of the lecture on “Cardiac contractility and the events of the cardiac cycle”.

Question 18

How far do muscle twitches spread in cardiac muscle ?

Answer 18

Cardiac twitches involve all fibers of the myocardium

Question 19

What happens when another contraction begins during the relative refractory period ?

Answer 19

Early premature contraction (or late premature contraction, depending how close to resting membrane potential)

Question 20

Draw graphs for the force generated by the heart in an early premature contraction, and in the late premature contraction.

Answer 20

Refer to slide 8 of lectures on “Cardiac contractility and the events of the cardiac cycle”.

Question 21

What is the effect on force of contraction, and cardiac output, and BP of early premature contractions and late premature contractions respectively ?

Answer 21

Early premature contraction: Lower force of contraction, lower output, lower BP
Late premature contraction: Same force of contraction, same output, same BP

Question 22

Draw a graph showing: 
1. Aortic P
2. Atrial P 
3. Ventricular P 
4. ventricular V
5. electrocardiogram 
6. phonocardiogram
as a function of time, showing the main events in the cardiac cycle.

Answer 22

Refer to slide 9 of lectures on “Cardiac contractility and the events of the cardiac cycle”.

Question 23

How many fibers of the heart myocardium are used in heart beats for force production?

Answer 23

Force production in the heart involves all myocardial fibres in every beat

Question 24

Describe the events of the cardiac cycle (with a focus on the left side of the heart), including explanations on changes in pressure in the different chambers of the heart.

Answer 24

DIASTOLE: As ventricle is relaxed and atria is relaxed, getting a passive filling of the ventricle.

ATRIAL SYSTOLE: Atria contracts, pushing last bit of blood into ventricle

VENTRICULAR SYSTOLE: Pressure is pretty low inside ventricle despite filling by blood (because quite compliant). When atria contracts, get a bit of increase in P (because some force of atria pushing more blood in over small period of time). This also causes an increase in atrial P (because contracting and pushing blood forwards). Ventricular contraction occurs and ventricular pressure therefore increases (initially, isovolumetric contraction during which only pressure changes in ventricle, not volume). However, aorta is elastic so lot of recoil (not v compliant), so P inside aorta is high whereas in ventricle it’s about 0, which is keeping aortic valve closed. Ventricular P builds, until it finally gets above that of the aorta, then blood gets ejected out as the valve opens. At that point, ventricle is still contracting (still generating a pressure) to push blood forward. As ventricle relaxes, pressure of aorta starts to exceed that of the ventricle and so aortic valve snaps shut.Then, eventually, P of ventricle is lower than that of the atria, and that AV valve can open and start the process of filling again. Period between aortic valve closure and AV valve opening is isovolumetric relaxation (drop in pressure of ventricle without change in volume).

Question 25

What are isovolumic contractions.

Answer 25

Volume doesn’t change but Pressure does

Question 26

Explain when the QRS complex takes place relative to ventricular contraction.

Answer 26

QRS complex precedes ventricular contraction because electrical event precedes when the contractile event occurs

Question 27

What are the “rebounds” in pressure of aorta, atria and ventricles due to ?

Answer 27

When you have valves closing, you either have the ventricles contracting and pushing blood against atria, causing transient increase in P OR rebound of blood against aortic valve that’s closed due to the elasticity of the aorta.

Question 28

How much of the left ventricular filling is passive and how much is due to atrial contraction ?

Answer 28

– ~80% of ventricular filling is passive due to normal blood flow
– Atrial contraction ‘tops up’ remaining ~20% volume

Question 29

How quickly does the ventricle pump blood ?

Answer 29

– Period of rapid ejection (1/3) when 70% of stroke volume ejected
– Period of slow ejection (2/3) when remaining 30% ejected

Question 30

What is the Systolic blood pressure in the aorta ?

Answer 30

120 mmHg

Question 31

What is the Diastolic blood pressure in the aorta ?

Answer 31

80 mmHg

Question 32

What are the main differences between systemic and pulmonary circulations, wrt pressure ? Why ? What are the consequences of this on the right side of the heart ?

Answer 32

Pressure in pulmonary circulation is much lower (but cycle works in the same way) because much less resistance to flow.
Hence, right side of heart needs to do less work and therefore right ventricle walls contain less muscle mass

Question 33

What is the pulmonary systolic pressure ?

Answer 33

30 mmHg

Question 34

What is the pulmonary diastolic pressure ?

Answer 34

12 mmHg

Question 35

Define End systolic volume (ESV).

Answer 35

Volume in ventricle at the end of systole

Question 36

Define End diastolic volume (EDV).

Answer 36

Volume in ventricle at the end of diastole

Question 37

Define stroke volume. Give a formula for it.

Answer 37

Quantity of blood expelled per beat (L).

EDV - ESV

Question 38

Define cardiac output. Give a formula for it.

Answer 38

Volume of blood pumped by the heart (L/min)

SV x HR

Question 39

Graph left ventricular P as a function of left ventricular volume, showing a full cardiac cycle including valve closing and opening, isovolumetric contraction and relaxation, EDV, ESV, and stroke volume.

Answer 39

Refer to slide 12 on lecture on “Cardiac Contractility”