Excitation Contraction Coupling

Question 1

What are the similarities and differences between skeletal and cardiac muscle?

Answer 1

Similarities-
both cardiac (extracellular and skeletal muscle: source of activating calcium is in Sarcoplasmic Reticulum
site of calcium regulation- is TROPONIN in both
differences, both has striations and t-tubules/sarcomeres
Skeletal muscle- no spontaneous electrical activity, NO gap junctions, no activity spreads between cells. extent of innervation- each cell (motor neuron), nerve stimulation leads to excite contraction, fast and slow speed of contractions, small effect of hormone on contraction

Cardiac muscle- spontaneous electrical activity (SA node), many gap junctions, activity spreads between cells, variable innervations (Autonomic nervous system). has excitation or inhibition effect: excitation of sympathetic nerves increase HR and contractility; parasympathetic decrease HR and decrease contractility, slow speed of contractions , large effect of hormones on contraction.

Question 2

Describe what twitch force is? What is the effect of adding drug Diltiazem on Cardiac AP and Twitch force?

Answer 2

Twitch- measure of the force of contraction
The drug Diltizem blocks Ca+ channel causing plateau phase (phase 2 of AP) to gets SHORTER.
Using Dialtezem drug inhibits contraction of muscle. The calcium that comes in during plateau phase of AP is important to causing contraction of cardiac muscle.
important in regulating activity and strength of contraction of cardiac muscle.

Question 3

What are t-tubules? Where is Calcium stored?

Answer 3

T-tubules- invaginations of the cell membrane where they communicate to extracellular space
AP travels down t-tubule, when cardiac membrane depolarizes, opening up Calcium channels along membrane
Sarcoplasmic reticulum- where calcium is stored in the cell
Ca+ very tightly regulated

Question 4

Why is there a rich supply of mitochondria in cardio myocytes. Distinguish systolic and diastolic.

Answer 4

rich supply of mitochondria because heart undergoes a lot of metabolic activity and uses a lot of ATP (oxidative actions)
systole- contraction of muscle (cardiac muscle contract and shortening), Ca+ must be made available
Diastole-relaxation phase (filling phase), Ca+ must be away from troponin (move Ca+ out of cell).

Question 5

What causes Ca+ channels in systolic?

Answer 5

change in voltage (-10 and +10), is when Ca+ channels open.
Fast Na+ channels change voltage from RMP (-90) to go up to -10 and +10. Once voltage gets to this range, Ca+ channels open and Ca+ moves extracellular to intracellular.
Ca+ that moves in during plateau phase (phase 2)
But for contraction to occur need more Ca+:
Calcium ions binds to channels on sarcopasmic retiuclum called Ryanodine (calcium induce ca+ release) opens up Ca+ channel allowing calcium to leave storage site (SR) and into cytoplasm and increase Ca+ [ ] in cell.
systolic phase caused by AP, depolarization of heart. Ca+ channels do not open unless membrane depolarizes due to SA nodal AP.

Question 6

What permits cardiac muscle to relax? What are the mechanisms involved? Why is relaxation important?

Answer 6

to get calcium back into storage site (SR) or back into extracellular space:
get calcium from cytosol back into SR:
1. use Ca+ ATPase on SR. it pumps calcium back into SR.
2. Na+ Ca+ exchanger: exchange 3 Na+ ions for Calcium to pump Calcium out into extracellular space
3. Ca+ pump on Sarcolemma- uses ATP to pump Ca+ ions from cytosol into extracellular space.
Relaxation is important because ventricle has to refill with blood between each heartbeat.
heart must be efficient in contracting and relaxing.

Question 7

How do you increase Cardiac Output during Exercise?

Answer 7

Increase Cardiac Output: increase both HR and Stroke Volume.
Stimulate Sympathetic Nervous system (release NE, bind B1 receptor, increase slope of prepotential, increase HR)
increase stroke volume during exercise
-each time heart contracts, empties 80% bloods ( efficient contraction). Do this by increasing Ca+ cycle
When NE and E binds to Beta 1 receptor causes activation of adenylate cyclase and increase in cAMP(2nd messenger)
High cAMP levels stimulate cAMP dependent protein kinase which phosphorylate Ca+ channel site
phosphorylate Ca+ channel, the channel stays open longer and conducts more Ca+ into the cell, more Ca+ ions bind to more ryanodine channel release Ca to SR, more Ca+ bind to troponin , more efficient contraction (empty 80% of blood), increasing SV and increasing CO.

Question 8

How can you enhance relaxation of cardiac muscle to support sustained contraction during exercise? what are the mechanisms used?

Answer 8

during exercise HR increases a lot (pump out more blood) and heart has to relax very efficiently, less time fill with blood.
enhance relaxation to support sustained increase of CO:
increase cAMP dependent protein kinase phosphorylate Phospholamban
Phospholamban- regulatory protein that normally inhibits Calcium channel.
When phosphorylate phospholamban you decrease inhibition of Calcium channel. Enhance Activity of Ca+ pump and pump Ca+ back into SR faster which helps get Calcium back into SR, and relax (ventricles refill with blood)
Troponin I- also gets phosphorylated by cAMP protein kinase
phosphorylate troponin I, reduces Ca+ affinity for troponin C (Ca+ won’t bind as tightly ), Ca+ released from troponin more quickly and enhance relaxation of cardiac muscle.
Both phosphorylating PHOSPHOLAMABAN and TROPININ I will enhance relaxation of cardiac muscle cell during exercise.

Question 9

What is the role of Cardiac Glycoside like digitalis? What is a negative effect of Digitalis?

Answer 9

Cardiac glycoside like Digitalis are given to patients who suffer from heart failure.
Digitalis- helps stimulate failing ventricles to contract more efficiently. enhances ability of cardiac muscles to contract.
Cardiac glycoside- blocks Na+ K+ pump. inhibiting this pump will increase contractile efficiency of heart: decrease Na [ ] outside cell, causing less Na+ gradient to exchange Na+ for Calcium and lead to increase in Ca+ inside cell and promote better contraction.
Negative effect of Digitalis: cardiac glycosides ONLY enhances contractile phase (no effect on relaxation) Not a problem for patient with heart failure.

Question 10

How can you inactivate the adenylate cyclase? How does this affect the cardiac cells?

Answer 10

muscarinic receptor that binds to Acetylcholine will activate inhibitory subunit of G protein, DECREASE cAMP levels.
ACh will decrease HR and force of contraction in the heart.
Norepinephrine increases HR and force of contraction.

Question 11

Define preload. Distinguish between preload in skeletal vs cardiac muscle. What is End-diastolic Volume?

Answer 11

Preload- force present in a RELAXED muscle
in vitro (lab)- preload- is weight attached to muscle to stretch it. length at which you get max contraction for skeletal muscle.
preload in Skeletal muscle- set at fixed length (initial stretching of cardiomyocyte before contraction)
preload in Cardiac muscle- determined by Venous pressure in End-diastolic volume sets the preload.
EDV- amount of blood in the ventricle at the end of filling phase
the Preload of Left and right ventricle based on amount of blood that fills the ventricle prior to being able to contract

Question 12

What are the positive and negative effects on cardiac output?

Answer 12

Preload and contractility have positive effects on Stroke Volume (increase SV)
increases Afterload has a negative effect: REDUCES SV and limits CO.
Heart rate increases Cardiac output

Question 13

What is Afterload? How does it differ in vitro vs in vivo? what determines the afterload of RV and LV?

Answer 13

Afterload- the force exerted by a SHORTENING muscle
in vitro- determined by applied load
in vivo (body)- determined by ARTERIAL pressure
(systemic arterial pressure for LV and pulmonary arterial pressure for RV)
- afterload- a force that opposes shortening of the muscle
afterload on RV and LV: determined by pressure of pulmonary artery on RV and pressure of aorta on LV.
RV will not be able to empty out blood until it generates more pressure than Pulmonic artery to open pulmonic valve (same for LV and aorta)
these pressures oppose emptying of ventricle.

Question 14

Define the Frank Starling relationship

Answer 14

Frank-starling relationship- as you increase the preload in the heart, it contracts more efficiently and ejects more blood out (since its getting closer to optimal length) . more blood delivered to ventricle, it will pump blood out into circulation.
Frank-starling- describes the length dependent changes (preload) in cardiac performance

Question 15

What is optimal length?

Answer 15

L0 (optimal or resting) length: sarcomere length where you get the maximum force development.
Skeletal muscle always set at its optimal length
Cardiac muscle- set at LESS than its optimal length.
more you fill the ventricle, the better it contracts.
at optimal length get maximum shortening.
preload- measure of how close you are to optimal length (fill ventricle to optimal length, you will get max CO).

Question 16

What is contracitlity? How is related to preload and afterload. What can increase contractility?

Answer 16

Contracitlity- variable state of muscle performance(force, velocity) at a given muscle length.
Contractility is INDEPENDENT of length and preload
related to Maximum velocity of shortening.
no matter what length the muscle is stretched to, if you increase contractility, you can make muscle contract more efficiently.
increase calcium availability, you can increase contraction at any resting length.

Question 17

How does Frank-starling theory and Contractility differ?

Answer 17

Frank starling- change length/stretch it more, it contract better
contractility- we can keep muscle at same length, and if more calcium available, still contract more efficiently at any length.

Question 18

What increases contractility?

Answer 18

Contractility- is the performance at a given preload and afterload
An increase in contractility occurs when myocardial fiber length (preload) remains Constant and developed Pressure and velocity of Shortening (increased cross bridge cycling) are INCREASED
NOT dependent on LENGTH.

Question 19

What is a positive inotropic effect

Answer 19

Positive inotrope effect- increase in contractility.
Exercise: increase CO:
increase HR by increasing sympathetic stimulation, increase rate of depolarization
increase stroke volume using Frank-starling: (by returning more volume to heart and stretching it more, for greater SV (amount of blood pumped out)
Also if we increase contractility by releasing more calcium increase CO.
Combine frank starling mech and contractility leads to even greater increase SV and hence CO.,

Question 20

What are the two ways you can increase Cardiac output during exercise using contractility and Frank-Starling?

Answer 20

increase HR by increasing sympathetic stimulation, increase rate of depolarization
increase stroke volume using Frank-starling: (by returning more volume to heart and stretching it more, for greater SV (amount of blood pumped out)
Also if we increase contractility by releasing more calcium increase CO.
Combine frank starling mech and contractility leads to even greater increase SV and hence CO.,

Question 21

How do you measure Contractility?

Answer 21

Contractility measured by( DP/dt) rate at which pressure increases
add positive inotrope (E/NE): INCREASE pressure at FASTER rate, and increase contractility (slope of prepotential steeper)

Answer 22

diastole- relaxation, filling phase; blood is refilling ventricles, calcium sequestered in storage sites or Ca pumped out into extracellular space
Chronotrope- anything that affects Heart rate
positive chronotrope- increases heart rate
ex: Sympathetic stimulation (Norepinephrine release), and Epinephrine
negative chronotrope- decreases heart rate
ex: Acetylcholine (bind to muscarinic, decreases slope)

Question 23

What is the Cardiac Cycle? What are the different phase of the cycle?

Answer 23

Cardiac cycle- phases of cardiac function that occur between each heart beat (70 x per min)
Phases:
1. Atrial Systole- contraction of the atria
2. Isovolumic contraction- contraction of ventricle, NO change in volume
3. Rapid ejection- ejection of blood volume
4. reduced ejection
5.Isovolumic relaxation
6. rapid filling
7. reduced filling
1 cardiac cycle= 1 circuit around the loop
both LV and RV experience 7 phases at the same time.(RV generates left pressure though)

Question 24

What is a Wigger’s Diagram

Answer 24

Wigger’s Diagram- puts all the sequential events of cardiac cycle of LV in place
Electrical activity proceed mechanical activity.
membranes depolarize before muscle shortens
Cardiac cycle starts from left to right

Question 25

What

Answer 25

start with SA node depolarizes and AP moves next to Atria.
then, atrial contraction occurs (forcing blood into left ventricle).
This is beginning of isovolumic contraction: where pressure in left ventricle begins to rise (Cardiomyocytes depolarize, Calcium comes in, and binds troponin) causing ventricles to shorten and contract, leading to increase in pressure
Once pressure rises in LV, blood will try and get back into LA, so mitral valve closes.
Isovolumic- aortic valves closed, so blood cannot go anywhere, but ventricular muscle is still shortening and compressing blood (decreasing chamber size), leading to pressure rising (80 mm Hg) pressure in left ventricle exceeds pressure of aorta, which causes aortic valve to open and blood flow from LV to Aorta.
During rapid ejection phase- aortic valve open and now volume is leaving ventricle (Ejecting blood out of aorta); pressure in LV and pressure in aorta are almost equal during rapid ejection and reduced ejection
Reduced ejection- aorta valve closes, at end of reduced ejection because pressure in aorta is slightly higher than pressure in ventricle snapping aortic valve close. The pressure in left ventricle drops during isovolumic relaxation due to Calcium being pumped back into SR, get calcium out of cytosol so muscle relax.
As muscle relaxes, pressure drops in left ventricle (aortic and mitral valve closed)
pressure in left ventricle drops to pressure lower than left atrium, causing mitral valve to open again, allows blood to fill ventricle
rapid ventricular filling
reduced filling
come back to atrial systole
changes in ventricular pressure tied to what occurs in AP and SA node in ventricle.
pressure in aorta fluctuates between 120/80.
pressure in aorta only drops to 80: due to arterioles that are offering resistance to flow and keep pressure in aorta to drop to only 80
if peripheral arteriole, dilates more, pressure drops even more.
pressure in aorta dependent on how constricted arterioles are.

Afterload of ventricle= aortic pressure (pressure keeping aortic valve closed)
patient with hypertension- patient was 150/110
patient’s aortic valve open at 110, so for every heart beat heart generate 30 mm Hg more pressure to open valve. (increasing the work of heart for each heartbeat). Why hypertension causes hypertrophy (heart thicker), lead to heart failure.
Pressure to change from 80 mm Hg to 120 mm Hg: force volume into aorta, cause pressure to increase
transfer volume from LV to aorta: cause
increase stroke volume- increase in pressure
aortic pressure is dependent on stroke volume

Left atrial pressure is always low, when atrial contracts, pressure in atria increases, then pressure low during isovolumic contraction
rapid ejection: LA pressure increases while ventricles contracting, atria are accumulating volume and increasing pressure and relaxing

Question 26

When is aortic blood flow highest?

Answer 26

During rapid ejection (when ventricle is forcing blood out into aorta) and reduced ejection

Question 27

Describe what happens in each phase of the cardiac cycle, including the changes in pressure.

Answer 27

Initially, SA node depolarizes and sends AP moves across atria
1. Atrial Systole- atrial contraction - atria contracts and forces blood into LV. (left ventricular pressure and right atrial pressure are the same
2. Isovolumic contraction- Left ventricular pressure rises (b/c ventricle starts to contract/shorten) at beginning of this stage. As the pressure rises, the mitral valve closes (prevent blood from flowing into atria). blood cannot go anywhere, but ventricle muscle still shortening causing pressure to rise.
3. Rapid ejection- at 80 mm Hg, pressure in LV, becomes higher than pressure of aorta, and aortic valve opens, allowing blood flow out from left Ventricle to aorta (volume leaves ventricle, eject blood to aorta). pressure in LV and pressure in aorta are equal
4. reduced ejection- blood ejected out into aorta, now at end of reduced ejection phase, aortic valve closes due to pressure in aorta being higher than pressure in ventricle, so direction of blood flow reverses (change in pressure and direction of blood flow cause aortic valve close)
5.Isovolumic relaxation- pressure in left ventricle drops because calcium is being pumped back into SR, or exchanged for Na into extracellular space. Calcium is out of cytosol, so muscle relaxes.
as muscle relaxes, pressure drops in left ventricle (aortic and mitral valve closed)
6. rapid filling- pressure in left ventricle drops to pressure lower than left atrial pressure, so mitral valve opens (allow blood fill ventricle)
7. reduced filling- ventricle refills with blood and you go back to atrial systole, start all over again.

Question 28

What would happen in the cardiac cycle of a patient with hypertension of blood pressure of 150/110? How does this affect the heart?

Answer 28

normal aortic pressure fluctuates between 120 and 80 mm Hg.
patient with hypertension (Bp; 150/110): aortic valve would open at a pressure of 110. so for every heart beat, heart would have generate 30 mm more pressure (than normal) before, aortic valve would open.
The heart has to work harder for each heartbeat.
Hypertension causes heart to hypertrophy (heart get thicker, set up pathological changes) that may lead to heart failure.

Question 29

What would represent afterload in cardiac cycle?

Answer 29

Afterload on ventricle- force that opposes emptying or contraction of ventricle
afterload - aortic pressure (keeps aortic valve closed)

Question 30

What would represent afterload in ventricle cardiac cycle?

Answer 30

Afterload on ventricle- force that opposes emptying or contraction of ventricle
afterload - aortic pressure (keeps aortic valve closed)

Question 31

What causes the pressure in aorta to increase from 80 mm Hg to 120 mm Hg?

Answer 31

aortic pressure increases from 80 to 120 because of transferring blood volume from LV to aorta, forcing blood volume into aorta, and causes aortic pressure to increase. r

Question 32

What happens to aortic pressure change , if you increase stroke volume?

Answer 32

the aortic pressure will increase(may double).

hence change in aortic pressure is dependent on stroke volume

Question 33

Why is Left atrial pressure increasing when ventricles relax and contract?

Answer 33

During rapid ejection and isovolumic relaxation- pressure in atria is gradually increasing.
LA pressure increases while ventricle is contracting and relaxing, because blood always come back from venous side to right and left atria.
while the ventricle is contracting, the atria is accumulating volume, which leads to pressure increase, so when LV pressure drops below atrial pressure, mitral valve open.

Question 34

Does volume increase or stay the same during atrial contraction? what about isovolumic contraction?
Distinguish between EDV and ESV in left ventricle. How do they relate to preload?

Answer 34

ventricular volume- during contraction of atria the volume increases, because you are forcing some blood into ventricle.
during isovolumic contraction- volume in ventricle stays the same (Left ventricular end diastolic volume or LVEDV)
LVEDV- volume in ventricle at the end of filling phase (max volume prior to contraction)
LVESV- volume in ventricle at end of contraction
SV= EDV- ESV
EDV= PRELOAD (volume in ventricle, set initial stretch)

Question 35

When does the first heart sound occur? When does second heart sound occur? What do third and fourth sounds represent in the heart and when do they occur?

Answer 35

First heart sound occurs at isovolumic contraction and when mitral valve closes (normal) Second heart sound- when aortic valve closes (normal)
The 3rd and 4th heart sounds are ABNORMAL.
3rd sound-occurs during rapid filling phase (heard in patients with congested heart failure) due to large volume in ventricle, and ventricle not contracting very well, compliance reduced.
4th heart sound- heard during atrial systole; in patients who have long standing hypertension, hypertrophied ventricle (ventricle less compliant) atrial contract and force blood into ventricle, hear sound.

Question 36

What is venous pressure pulse?

Answer 36

Venous pressure pulse- central venous pulse; low pressure (< 5 mm Hg); A C and D wave forms
venous pressure pulse follows Left atrial pressure signal
P, QRS and T wave. P wave starts before atrial contracts,
QRS complex- ventricular depolarization occurs before isovolumic contraction, and ventricles begin to contract

Question 37

How long does heart spend in diastole vs systole?

Answer 37

Heart spends 2/3 of its time in diastole and 1/3 of its time in systole.

Question 38

How do you determine Cardiac output by looking at Wigger’s Diagram? How would you calculate Ejection Fraction?

Answer 38

CO= HR x SV
to find HR: look at time value on graph from 1st p wave to next p wave (0 to 0.8). Divide 60 secs by the time for p wave. ex: (60/0.8 = 75 beats per minute)
To find SV: EDV- ESV = 40 -20 to get 20 for SV
then CO= 75 x 20 = 1500 mL (or 1.5 L/min)
Dog has smaller heart (pumps less volume).
EF= SV/EDV= 20/40 = 50%.

Question 39

What are the pressure values for RA, LA, peak systolic RV, peak systolic LV, and Pulmonary wedge pressure?

Answer 39

Mean RA pressure- 3 mm Hg
peak systolic RV pressure- 25 mm Hg
LA pressure- 8 mm Hg
Peak systolic LV pressure- 130 mm Hg
Pulmonary capillary wedge pressure (index of LA pressure)- 9 mm Hg.

Question 40

What is another way to represent cardiac cycle?

Answer 40

Pressure volume loop- another way represent cardiac cycle (LV pressure on y axis and LV volume on x-axis).
1 cardiac cycle= 1 circuit around volume loop.

Question 41

Where would you find preload in the pressure volume loop? Where would afterload start?

Answer 41

Preload would be bottom right of graph (around 150). since preload is the maximum volume in ventricle prior to contraction.
afterload would start around 80mm Hg (when aortic valve open), and then be between 80 and 120 mm Hg.
since afterload is the force ventricle has to overcome to empty)

Question 42

What phases of cardiac cycle determine preload? What do you notice in isovolumic contraction on volume loop?

Answer 42

rapid filling, slow filling and atrial contraction determine preload.
Isovolumic contraction phase- pressure increases, but volume stays the same.
at 80 mm Hg, aortic valve opens because ventricular pressure exceeds aortic pressure causing rapid ejection and reduced ejection of blood into aorta.
The rise in pressure during ejection then causes aortic valve to close.
This leads to isovolumic relaxation- where pressure drops, but volume stays the same.

Question 43

What is seen at the value of 150 in pressure-volume loop? What about 50? What would be the stroke volume? What would be ejection fraction?

Answer 43

at 150 you see End diastolic Volume (another term for preload). At 50 you are seeing End Systolic Volume)
SV: EDV- ESV= 150 -50; so SV= 100.
EF: SV/EDV= 100/150 = 67%.

Question 44

What happens when you change preload, afterload and contractility? What is the effect on pressure-volume loop?

Answer 44

change preload- if you INCREASE preload, INCREASE SV (putting more blood in ventricle, stretching to optimal length, so when it contracts, you will pump out extra volume). Here ESV stays the same, but you increase EDV to increase SV.
change afterload- INCREASE Afterload DECREASE SV.
since you will have to increase the pressure ventricle has to achieve to open aortic valve (heart has to use more energy to generate higher pressure, so it will shorten/contract less and eject less blood.
change contractility-INCREASE Contractility, INCREASE SV.
with increasing contractility, length stays the same (preload not affected), but release more calcium, and shorten/contract more efficiently and empty more volume. You are reducing ESV, to increase SV.

Question 45

How is the ventricle able to maintain a constant SV in the time of Increased Afterload? How can this be a problem?

Answer 45

It increases preload (more volume left in ventricle), during next venous return, fill ventricle to a larger volume, streach it more (increase preload), and ventricle will deliver the same stroke volume at higher pressure.
Problem: heart has to do more work to deliver the same stroke volume with higher pressure. so wall stress on the heart is elevated. > wall stress on heart than normal.
hence patient with hypertension may deliver a normal SV, it is more metabolically expensive for heart, increase wall stress, can lead to hypertrophy and then lead to failure of ventricle.

Question 46

What occurs in pressure volume loop with patient who has heart failure?

Answer 46

patient’s ventricle is failing: Stroke volume look the same in patient vs normal. However, pressure volume loop has shifted to the RIGHT(more volume in ventricle) so it operates at its maximal length, high volume.
so if you increase afterload with a person who has failing ventricle, will not be able to increase preload because it already reached maximum preload.
pressure volume loop narrow, and stroke volume drops.
Failing ventricle- very afterload-dependent, so one way to help patient failing ventricle, and increase afterload, is give patient vasodilator (reduce peripheral resistance and lower afterload, allow ventricle function more efficiently.

Question 47

Describe what occurs in a patient with hypertension untreated

Answer 47

hypertrophic -efficient pressure pump, NOT very efficient volume pump. (pressure-volume loop shifts left); they can generate high pressure to overcome high afterload, but volume in ventricle is reduced (due to wall stress, and hypertrophy) Hypertrophic graph (has thickened walls, small chamber size)

Dilated cardiomyopathy, in stage congested heart failure: patients pressure volume loop shift right; a lot of volume in ventricle, but when ventricle stimulated to contract, it does not empty a lot of volume because it has systolic failure (not ejecting much volume, during contraction). dilated cardiomyo has lowest stroke volume/Ejection fraction (thickened chamber, deliver low stroke volume when contracts)
Diuretic- decrease preload; vasodilator decreases afterload.