Cardiovascular mechanics Flashcards
What is excitation-contraction coupling?
Process whereby the excitatory event turns into the contractile event via a series of processes
Describe a single ventricular event
Electrical event
Ca2+ influx
Ca2+ release
Contractile event
How was the importance of calcium for the heart beat discovered?
Sydney Ringer
Saline solution with pipe water allowed the heart to contract
How big are ventricular cells?
100 μm long and 15 μm wide
What are t-tubules?
Finger-like invaginations from the cell surface
Carry surface level depolarisation into the heart of the cell
How big are t-tubules?
T-tubule openings up to 200 nm in diameter
Spaced (approx. 2 μm apart) so that a T-tubule lies alongside each Z-line of every myofibril
What percentage of cell volume do myofibrils occupy?
46%
Why are there so many mitochondria in muscle cells?
Provide ATP for muscle contraction
What key calcium handling proteins are in the t-tubules?
L-type calcium channel
What causes the L-type calcium channels to open?
Response to the action potential arriving
Calcium moves into cell down concentration gradient
Where does calcium go after entering the cell?
Binds to SR Ca2+ (ryanodine receptor) release channel
What does Ca2+ binding result in?
Conformational change
Allows calcium to flow from the sarcoplasmic reticulum into the cytosol
How is relaxation induced?
ATP is used to restore calcium into the sarcoplasmic reticulum
What is the sodium/calcium exchange system?
Doesn’t use ATP
Uses the downhill energy gradient of Sodium to expel calcium out of the cell
What happens as more and more calcium enters the cell?
More force produced
Activation of more myofilaments
Sigmoidalish relationship
What happens when you lengthen a muscle?
More force produced with increasing length
Baseline force also increases
‘Active force production line”
What happens to elastic component when lengthened?
Elastic components stretch
Passive force produced
What is isometric contraction?
Non-shortening force production
Muscle fibres do not change length but pressures increase in both ventricles
How is cardiac and skeletal muscle different?
Cardiac muscle more resistant to stretch and less compliant than skeletal muscle
Less passive force in skeletal muscle
What causes this difference in skeletal and cardiac properties?
Due to properties of the extracellular matrix and cytoskeleton
What is unique about cardiac muscle?
It cannot be overstretched as the heart is contained in the pericardial sac that does not allow it to overstretch
Therefore Only ascending limb of the relation is important for cardiac muscle
What is isotonic contraction?
Shortening of fibres and blood is ejected from ventricles
What contraction is involved in the cardiac cycle?
Under normal circumstances: both isometric and isotonic
Define preload
Weight that stretches muscle before it is stimulated to contract
Define after load
Weight not apparent to muscle in resting state; only encountered when muscle has started to contract
What is the relationship between shortening and load in isotonic contraction?
If load is great the shortening the muscle can do is very small
What is the relationship between muscle length (preloaded) and stretch?
More interdigitation of the fibres occur, more stretch with length
What is the in vivo correlate of preload?
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
What are measures of preload?
End-diastolic volume
End-diastolic pressure
Right atrial pressure
What are the in vivo correlates of after load?
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.
What is the measure of after load?
Diastolic blood pressure
Why is it important to keep diastolic pressure low?
That is the pressure against the heart to work to eject blood
If diastolic blood pressure is high then the heart has to do more work
What happens as filling of the heart increases?
Force of contraction increases
Define the frank-starling relationship?
Increased diastolic fibre length increases ventricular contraction
What is the consequence of the F-S relationship?
Ventricles pump greater stroke volume so that, at equilibrium, cardiac output exactly balances the augmented venous return
What are the factors causing the F-S relationship?
Changes in the number of myofilament cross bridges that interact
Changes in the Ca2+ sensitivity of the myofilaments
How does the number of cross bridges interacting affect force?
As the muscle stretches
Allow for more cross bridges to form
Causes greater force
What happens at shorter lengths?
At shorter lengths than optimal the actin filaments overlap on themselves so reducing the number of myosin cross bridges that can be made
How does Ca2+ sensitivity affect force?
Hypothesis 1
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
How does Ca2+ sensitivity affect force?
Hypothesis 2
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
Define stroke work
Work done by heart to eject blood under pressure into aorta and pulmonary artery
What is stroke work equal to?
volume of blood ejected during each stroke (SV) multiplied by the pressure at which the blood is ejected (P)
SV x P
What affects stroke volume?
Preload and afterload
What affects pressure?
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
What is law tension equal to?
Pressure in vessel x Radius in vessel
T= P x R
Incorporating wall thickness (h), this can be amended to:
T= (PxR)/h
What is the significance of radius of curvature?
Radius of curvature of walls of LV less than that of RV allowing LV to generate higher pressures with similar wall stress
