Cardiac contractility and the events of the cardiac cycle Flashcards
Describe the molecular level of a cardiac muscle contraction.
- 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
- Release of Calcium activates troponin C. This takes tropomyosin away from the myosin binding sites on actin, enabling strong actin-myosin binding
Describe the molecular level of a cardiac muscle relaxation.
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
What is the difference in the diameter and volume of T tubules between those of skeletal and those of cardiac muscle ?
Cardiac muscle T-tubules 5x greater in diameter than sk. muscle (25x more volume)
Is Dihydropyridine to Ryanodine receptor linkage mechanical (such as is the case in sk. muscle) ?
No
Distinguish between cardiac and skeletal muscle with regards to whether they can achieve different forces of contraction ? Explain this difference on a molecular level.
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)
What is the effect of resting heart rate on force of contraction ?
At resting heart rates, ↑[Ca2+]i due to influx and sarcoplasmic release is insufficient to cause maximal contractile force.
Describe sympathetic innervation effect on cardiac muscle. Specifically, discuss the effects on Noradrenaline on cardiac muscle.
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
Describe how widespread in the heart the effects of the SNS and PSNS are respectively.
SNS: Throughout entire heart
PSNS: Mostly to SA Node (innervates atria)
Describe parasympathetic innervation effect on cardiac muscle
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
Graph a function of cardiac tension over time with sympathetic innervation, no innervation, and parasympathetic innervation. Explain the shapes of the different graphs.
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.
Rank sympathetic innervation, no innervation and PSNS innervation in increasing ionotropic state.
SNS > No innervation > PSNS
Why is it impossible to summate cardiac muscle contractions (tetanize cardiac muscle cells) ?
Because of refractory period
Define absolute refractory period, and relative refractory period. Why do they occur ?
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.
Define supranormal excitability.
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
How long is the period of contraction, and the refractory period in skeletal muscle ?
– Absolute refractory period 1-2ms
– Period of contraction 20-100ms
How long is the period of contraction, and the absolute refractory period in cardiac muscle ?
– Absolute refractory period (ARP) ~245ms
– Period of contraction 250ms
Draw a graph of an AP in cardiac muscle, clearly showing the ARP, RRP, and SNP.
Refer to slide 7 of the lecture on “Cardiac contractility and the events of the cardiac cycle”.
How far do muscle twitches spread in cardiac muscle ?
Cardiac twitches involve all fibers of the myocardium
What happens when another contraction begins during the relative refractory period ?
Early premature contraction (or late premature contraction, depending how close to resting membrane potential)
Draw graphs for the force generated by the heart in an early premature contraction, and in the late premature contraction.
Refer to slide 8 of lectures on “Cardiac contractility and the events of the cardiac cycle”.
What is the effect on force of contraction, and cardiac output, and BP of early premature contractions and late premature contractions respectively ?
Early premature contraction: Lower force of contraction, lower output, lower BP
Late premature contraction: Same force of contraction, same output, same BP
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.
Refer to slide 9 of lectures on “Cardiac contractility and the events of the cardiac cycle”.
How many fibers of the heart myocardium are used in heart beats for force production?
Force production in the heart involves all myocardial fibres in every beat
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.
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).
What are isovolumic contractions.
Volume doesn’t change but Pressure does
Explain when the QRS complex takes place relative to ventricular contraction.
QRS complex precedes ventricular contraction because electrical event precedes when the contractile event occurs
What are the “rebounds” in pressure of aorta, atria and ventricles due to ?
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.
How much of the left ventricular filling is passive and how much is due to atrial contraction ?
– ~80% of ventricular filling is passive due to normal blood flow
– Atrial contraction ‘tops up’ remaining ~20% volume
How quickly does the ventricle pump blood ?
– Period of rapid ejection (1/3) when 70% of stroke volume ejected
– Period of slow ejection (2/3) when remaining 30% ejected
What is the Systolic blood pressure in the aorta ?
120 mmHg
What is the Diastolic blood pressure in the aorta ?
80 mmHg
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 ?
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
What is the pulmonary systolic pressure ?
30 mmHg
What is the pulmonary diastolic pressure ?
12 mmHg
Define End systolic volume (ESV).
Volume in ventricle at the end of systole
Define End diastolic volume (EDV).
Volume in ventricle at the end of diastole
Define stroke volume. Give a formula for it.
Quantity of blood expelled per beat (L).
EDV - ESV
Define cardiac output. Give a formula for it.
Volume of blood pumped by the heart (L/min)
SV x HR
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.
Refer to slide 12 on lecture on “Cardiac Contractility”
