Cardiovascular mechanics Flashcards
How can you view a heart?
via magnetic resonance imaging (MRI)
How would you describe the structure of musle?
muscle-> muscle bundle-> muscle fibres-> myofibrils
What are cardiac myocytes?
Contain the smallest functional units of the cardiac muscle= sarcomeres (their contraction determines the contraction of the muscle)
What happens to a sarcomere during cardiac myocyte contraction?
Z lines= come closer together (sarcomere shrinks)
A band= remains the same length
H zone= disappears
I band= shrinks
What is the I band?
actin filaments only
What is the H band?
Myosin filaments only
What are in cardiac myocytes?
sarcolemma
T tubules (line up with the length of the sarcomere= in line with the Z lines)
Sarcoplasmic reticulum (Ca2+ store)
Mitochondria
Nucleus (single nucleus, striated muscle)
What is the process of excitation-contraction coupling?
- L-type Ca2+ channel senses depolarisation + opens in response to AP
- Ca ions move down conc. gradient into cell
- Most of Ca binds to SR Ca release channel (ryanodine receptor ->ligand binding) which causes release of Ca from SR Ca stores (calcium induced calcium release)
- Ca released from SR goes to myofilaments to trigger contraction (Ca2+/troponin complex)
- To trigger relaxation Ca is taken up again by SR via Ca ATPase which uses ATP to restore Ca levels in SR until next beat/contraction
- Ca levels inside cell restored by Na+/Ca2+ exchanger -> uses downhill energy gradient of Na rather than ATP to release Ca2+ outside of cell
How is Force (%max) linked to cytoplasmic Ca2+ concentration (microM)?
Where are L type receptors found?
Invaginations of T-tubules
What happens in a sarcomere during relaxation?
- Ca2+ ATPase into sarcoplasmic reticulum
- Na+/ Ca2+ exchanger into T tubule
What is the preload?
Weight that stretches the muscle before it is stimulated to contract
The initial stretch on the heart muscle as blood fills the chambers during diastole
What does preload depend on?
venous return
What is stretch determined on?
venous return and end diastolic volume
What is afterload?
Weight not apparent to muscle in resting state; only encountered when muscle has started to contract
Pressure against which the heart must eject blood during systole e.g., diastolic blood pressure
What does more afterload lead to?
more shortening
In vivo correlates preload and afterload with what?
As blood fills the heart during diastole, it stretches the resting ventricular walls
This stretch (filling) determines the preload on the ventricles before ejection
Preload is dependent on venous return (rate of blood flow back to the heart)
Afterload is the load against which the left ventricle ejects blood after opening of the aortic valve
Any increase in afterload decreases the amount of isotonic shortening that occurs and decreases the velocity of shortening
Measures of afterload include diastolic blood pressure
What are the factors that affect shortening?
Ventricular filling for isometric contraction
Pressure in the aorta for isotonic contraction
What is isotonic contraction?
increase in force with a shortening of muscle
what is isometric contraction?
increase in force without a change in length of myocyte
When does isometric contraction occur in the cardiac cycle?
No shortening of ventricles, during ISOVOLUMETRIC CONTRACTION
When does isotonic contraction occur in the cardiac cycle?
shortening of ventricles to eject blood, during RAPID EJECTION
This is a length-tension graph for which muscle?
This is a length-tension graph for which muscle?
What is total force?
passive force + active force
What is total force?
passive force + active force
How do you calculate passive force?
from recoil/ elastic energy
Why can the passive force only go to 100%?
Due to pericardium
What is total force?
passive force + active force
What is the correlation between force and preload in isometric contraction?
What is the correlation between shortening and afterload/ and velocity of shortening and afterload in isotonic contraction?
What happens if you have longer muscles/ sarcomeres?
They are more sensitive to Ca2+
What are the clinical measures of preload?
end-diastolic volume
end-diastolic pressure
right atrial pressure
What is the clinical measure of afterload?
diastolic blood pressure
How does an electrical event occur?
Ca2+ influx and Ca2+ release–> contractile event
How did we find out calcium is important for the heart beat?
If you use saline solution you don’t get the same effects as using pipe water (due to inorganic constituents of the pipe water)
Addition of lime or a calcium salt will restore good contractility
What is the structure of a single ventricular cell?
- Ventricular cells 100 micrometres long and 15 micrometres wide
- T-tubules are finger-like invaginations of the cell surface
- T-tubule openings up to 200nm in diameter
- Spaced (approximately 2 micrometres apart) so that a T-tubule lies alongside each Z line of every myofibril
What is the role of T-tubules?
They carry surface depolarisation deep into the cell
Why do cardiac cells have lots of mitcohndria?
they are v metabolically active
How much of the cardiac cell is made of myofibrils and mitchondria?
46% myofibril
36% mitochondria
What does an action potential lead to?
Calcium influx
What cell structure facilitates the transmission of an action potential to the centre of a cell?
T tutbules
What are sarcoplasmic reticulum Ca release channels known as?
ryanodine receptors (RyR)
What is the main intracellular calcium store?
Sarcoplasmic reticulum
What is muscle length proportional to?
Force produced
What leads to passive force?
elasticity component
Explain the differences between these graphs.
Cardiac muscle is more resistant to stretch and less compliant than skeletal muscle
- Due to properties of the extracellular matrix and cytoskeleton
- Only ascending limb of the relation is important for cardiac muscle
Increase in passive force in cardiac muscle compared to skeletal muscle
- This is because the elastic components in the ECM are more resistant to stretch and less compliant than in skeletal muscles
What are the types of contraction?
Isometric=> muscle fibres do not change length but exert force so pressures increase in both ventricles
Isotonic=> shortening of fibres and blood is ejected from ventricles
What does concentric mean?
the muscle tension rises to meet the resistance, then remains stable as the muscle shortens
What is the Frank-starling relationship?
Observation by frank (1895) and later by starling (1914) showed that as filling of the heart increased, the force of contraction also increased
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
What is the frank-starling relationship though to be caused by what 2 factors?
- changes in the number of myofilament cross bridges that interact
- changes in the Ca2+ sensitivity of the myofilaments
Describe the factor of “changes in the number of myofilament cross bridges that interact”.
At shorter lengths than optimal actin filaments overlap on themselves so reducing the number of myosin cross bridges that can be made.
How many hypothesis are there for “changes in the Ca2+ sensitivity of the myofilaments”?
2, precise mechanism is still unclear
What is the first hypothesis regarding “changes in the Ca2+ sensitivity of the myofilaments”?
hint: TnC
Ca2+ required for myofilament activation
Troponin C (TnC) is thin filament protein that binds
Ca2+
TnC regulates formation of cross-bridges between actin and myosin
At longer sarcomere lengths the affinity of TnC for Ca2+ is increased due to conformational change in protein
Less Ca2+ required for same amount of force
What is the second hypothesis regarding “changes in the Ca2+ sensitivity of the myofilaments”?
With stretch the spacing between myosin and actin filaments (so-called “lattice spacing”) decreases
With decreasing myofilament lattice spacing, the probability of forming strong binding cross-bridges increases
This produces more force for the same amount of activating calcium
What is stroke work?
Work done by the heart to eject blood under pressure into aorta and pulmonary artery
How do you calculate stroke work?
volume of blood ejected during each stroke (SV) x the pressure at which the blood is ejected (P)
SV x P
What influences stroke volume?
preload and afterload
What influences pressure (at which the blood is ejected)?
cardiac structure
What is the Law of LaPlace?
When the pressure within a cylinder is held constant, the tension on its walls increases with increasing radius
How do you calculate wall tension?
T= P x R
pressure in vessel x radius of vessel
How can you amend the equation T= P x R?
incorporating wall thickness (h)
T= (P x R)/ h
When can the Law of LaPlace be applied in the human heart?
- Radius of curvature of walls of LV less than that of RV allowing LV to generate higher pressures with similar wall stress
What happens in failing hearts regarding the Law of LaPlace?
often become dilated, which increases wall stress
What are non-human examples of application of Law of LaPlace?
