Cardiovascular mechanics 1 Flashcards
What shape do cardiomyocytes have
A rod shape
If we have a fluorescent dye that is sensitive to intracellular calcium, if the cell appears brighter, what does this show
That there is a higher concentration of calcium inside the cell
Describe the sequence of events that take place in a cardiomyocyte
Electrical event
Ca2+ influx, Ca2+ release
Contractile event
Describe the dimensions of cardiomyocytes
100 microns long
15 microns wide
What is calcium release also known as
The calcium transient, as it rises and falls over time.
Is the cell surface of cardiomyocytes smooth
No- as it is invaginated by T-tubules
What are the t-tubules and why are they important
T-tubules (transverse tubules) are finger-like invaginations from the cell surface
Carry surface depolarisation deep into the cell
What is the diameter of the t-tubule openings
About 200nm
What is the spacing of the T-tubules
Spaced (approx. 2 μm apart) so that a T-tubule lies alongside each Z-line of every myofibril
What is the major structure of the cardiomyocyte
The myofibrils
Why do cardiomyocytes have a large number of mitochondria
Because heart muscle requires a large and continuous supply of ATP to contract. They are located close to the functioning myofibrils.
Describe excitation-contraction coupling in the heart
Depolarisation sensed by L-type Ca2+ channel in the T-tubule. This causes the channel to open and Ca2+ enters the cardiomyocyte down its concentration gradient. Some calcium binds to Ryanodine receptors on SR- causing release of intracellular stores of calcium
Some calcium binds directly to troponin to cause contraction.
This is known as calcium induced-calcium release
Describe the key difference between cardiac muscle and skeletal muscle
Skeletal muscle would still contract even in the absence of extracellular calcium.
How do we transport Ca2+ out of the cell
The same amount of calcium that comes into the cell is effluxed out of the cell using the Na+/Ca2+ exchanger, which uses the downhill concentration of Na+ into the cell to drive the efflux of Ca2+. This occurs during relaxation. Important as you don’t want to lose conc gradients by loading all Ca2+ into the cell.
How else can we remove intracellular calcium
Ca2+ in the cytoplasm is taken up by the SR by the Ca2+ ATPase channels by active transport.
What is the relation between force production and intracellular calcium concentration
There is a complex relationship between intracellular calcium conc and force production. (S-shaped curve). It is a sigmoidal relationship. Around a 10 micromol intracellular concentration of calcium is enough to produce maximal force.
What is the role of a force transducer
To measure the amount of force
What happens as we stretch the muscle in
The amount of force produced increases- active force
The baseline level of force increases- passive force (baseline force at resting level).
Describe the relationship of muscle length with both active and passive force
As we increase the length of the muscle, active force production increases up to a point. Then the amount of active force produced starts to decrease as we continue to stretch the muscle beyond this point.
Proportional relationship with the amount of passive force produced.
What is meant by passive force
The passive force is the isometric contraction (no shortening) – just tension changes. It exists before the contraction.
Why does active force stop increasing after it has been stretched to a certain length.
As you keep stretching the muscle, a point is reached were stretching does NOT generate more force – due to not enough overlap between the filaments to produce force in contraction.
What type of muscle contractions occur in the cardiac cycle
Both isometric and isotonic.
What happens in a pulled/over-stretched muscle
The actin and myosin cannot overlap, hence no more force can be generated.
What are the key differences in the length-tension relation in cardiac and skeletal muscle cells
Cardiac muscle more resistant to stretch and less compliant than skeletal muscle- hence cardiac muscle cells have a larger passive force. This is due to properties of the extracellular matrix and cytoskeleton.
ONLY the ascending limb of the length-tension graph is important as the descending limb doesn’t happen in physiological conditions as the pericardium restricts the stretching
Describe isometric contraction in the heart
Muscle fibres do not change length but pressures increase in both ventricles- the fibres push against the blood- but cannot change length as the valves are closed.
Describe isotonic contraction in the heart
Shortening of fibres and blood is ejected from ventricles- valves open- can contract more than normal.
What is meant by preload
Weight that stretches muscle before it is stimulated to contract
What is meant by afterload
Weight not apparent to muscle in resting state; only encountered when muscle has started to contract
Afterload is the weight/mass/pressure that the muscle tries to overcome
In an isometric contraction, how is the force related to the preload
As preload (stretch) increases, the force produced increases. This occurs up to a point. Once this point has been exceeded, any further increases in preload will result in the muscle producing less force.
In an isotonic contraction, what is the relationship between the afterload and the amount of shortening
More afterload results in less shortening
What is the difference in the amount of shortening between different muscle lengths with the same afterload
Longer muscle lengths shorten more, hence larger preloads result in more shortening with the same afterload, and thus more force produced.
What governs the amount of force the muscle is capable of producing
The preload
What is the relationship between the afterload and the velocity of shortening
A larger afterload results in a lower velocity of shortening.
Describe the in vivo correlates of preload
As blood fills the heart during diastole, it stretches the resting ventricular walls- due to the pressure increasing
This stretch (filling) determines the preload on the ventricles before ejection
Preload is dependent on venous return
Measures of preload include end-diastolic volume, end-diastolic pressure and right atrial pressure
Describe the in vivo correlates of afterload
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 preload include diastolic blood pressure
Essentially, The afterload is the force that the heart must overcome to eject blood from the ventricles – resistance to flow of blood.
What happens if you are hypertensive
If you are hypertensive, the afterload is increased as there is a greater pressure in the heart. The ventricle has to work harder to open the semi-lunar valves and expel blood from the heart.
Describe the relationship between ventricular filling and the force produced in isometric contraction
More ventricular filling- more preload- more force produced
Describe the relationship between aortic pressure and shortening of the muscle fibres
Higher aortic pressure, more afterload, less shortening of the fibres. For increased ventricular filling, more shortening for the same aortic pressure.
What did the observations made by Frank and Starling show
Observations by Frank (1895) and later by Starling (1914) showed that as filling of the heart increased, the force of contraction also increased
Define the Frank-Starling relationship
Increased diastolic fibre length increases ventricular contraction. In other words, an increase in stretching (or preload) leads to an increase in shortening and speed of shortening.
Do longer or shorter fibres have a higher velocity of shortening for the same afterload
Longer
What is the consequence of the Frank-Starling relationship
Ventricles pump greater stroke volume so that, at equilibrium, cardiac output exactly balances the augmented venous return. In other words, blood coming in determines strength of ventricular contraction and hence determines volume of blood leaving the ventricles. This means the heart can ALWAYS pump out any volume of blood pumped in, it can adapt!
Describe the two factors that result in the Frank-starling relationship
o 1) Changes in the number of myofilament cross-bridges that interact. o 2) Changes in the calcium sensitivity of the myofilaments.
Explain how changes in the number of myofilament cross-bridges that interact leads to the Frank-Starling relationship.
At shorter lengths than optimal the actin filaments overlap on themselves so reducing the number of myosin cross bridges that can be made.
Explain how changes in the calcium sensitivity of the myofilaments leads to the Frank-Starling relationship
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
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 the equation for stroke work
Stoke volume (greatly influenced by afterload and preload) Pressure (influenced by the structure of the heart)
What is the stroke volume
The volume of blood ejected in each stroke
Define the law of LaPlace
When the pressure within a cylinder is held constant, the tension on its walls increases with increasing radius
What are the two equations for LaPlace
Wall Tension = Pressure in vessel x radius of vessel
Wall Tension = Pressure in vessel x radius of vessel divided by the thickness
Describe the consequences in the differences in the radius of curvature of the left and right ventricles
The radius of curvature of the walls of the LEFT ventricle is less of that of the RIGHT ventricle. o This allows the LV to generate high pressures with similar wall tension as T = PR.
How is wall tension kept low in the neck of giraffes
In giraffes, wall stress is kept low by the long, narrow, thick-walled ventricle which has a SMALL radius to generate HIGH pressure (blood to the head).
In frogs, how is pressure kept lower
In frogs, pressures are kept lower so the ventricles are almost spherical which makes a LARGE radius so a LOW pressure
Describe what happens in failing hearts
Failing hearts (dilated cardiomyopathy) display an enlarged radius which increases wall stress.
What is the law of LaPlace responsible for explaining
It describes why the heart doesn’t rip given the high internal pressures it creates
