6.3 - Cardiac Mechanics Flashcards
1
Q
What is excitation-contraction coupling?
A
- excitatory event (AP) at myocyte –> influx of Ca2+ –> Ca2+ release –> contraction
- contraction is very dependent on the influx of external Ca2+ - heart cell will not contract unless this happens
- cardiac APs are longer - important as length of AP dictates strength of contraction
2
Q
What is the length and width of myocytes?
A
- ventricular cells are 100um long and 15um wide
3
Q
What are T-tubules
A
- transverse tubules are finger-like invaginations of the cell surface
- spaced so that a T-tubule lies alongside each Z-line of every myofibril
- T-tubule openings are up to 200nm in diameter
- carry surface depolarisation deep into the cell
4
Q
What is the composition of a myocyte?
A
- 46% myofibrils
- 36% mitochondria - high energy requirement
- 4% sarcoplasmic reticulum
- 2% nucleus
- 12% other
5
Q
How does AP travel from cell surface into cell?
A
- AP produced along cell surface
- depolarisation carried deep into cell down T-tubule and sensed by many L-type Ca2+ channels (LTCCs) in T-tubules
- alters LTCC conformation and opens it so Ca2+ from outside of cell flows down its concentration gradient into the cytosol
- this Ca2+ binds to sarcoplasmic reticulum release channels (ligand operated) on SR that then open
- Ca2+ stored in SR released into cytosol - this Ca2+ binds to troponin in myofilaments and activates contraction
- to relax, Ca2+ is actively pumped against concentration gradient by SR Ca2+ ATPase into SR where it is ready to be released by next wave of depolarisation
- the Ca2+ that came into cell to trigger release of Ca2+ is removed from cell during diastolic interval by Na+/Ca2+ exchanger in T-tubule which uses downhill movement energy of Na+ into cell to pump Ca2+ out of cell
- myocyte now in Ca2+ balance
6
Q
What is the relationship between force production and intracellular Ca2+?
A
- we can increase Ca2+ in SR with e.g. sympathetic stimulation
- can increase phosphorylation of some proteins and increase Ca2+ influx into cell
- looks like sigmoid curve
7
Q
How does force produced change with muscle length?
A
- as you increase muscle length and stimulate it, you increase active force production due to cross bridge formation happening in response to Ca2+ being released from SR
- cardiac cells also have some elasticity so have a tendency to recoil as they are stretched - meaning as you increase muscle length, base force produced increases too (called passive force)
8
Q
What is length-tension relation in cardiac vs skeletal muscle?
A
- initially as length increases, total force increases
- after a certain length, active force and total force decreases in both
- passive force increases as muscle length increases
- total force = active + passive
9
Q
Why does cardiac muscle produce more passive force?
A
- cardiac muscle is more resistant to stretch and less compliant than skeletal muscle
- due to properties of the ECM and cytoskeleton
10
Q
What does it mean that the cardiac muscle only works on the ascending limb of the length-tension relationship?
A
- you cannot overstretch cardiac muscle - you can with skeletal muscle (where you pull myofibrils apart)
- heart is contained in pericardial sac so you can only stretch a certain amount
11
Q
What is isometric contraction?
A
- muscle fibres do not change length but exert force so pressure increases in both ventricles
- when ventricles fill with blood we get isometric contraction and valves are closed so blood does not go anywhere = builds up ventricular pressure
- happens in planks
12
Q
What is isotonic contraction?
A
- shortening of fibres and blood is ejected from ventricles
- when pressure in ventricles from isometric contraction overcomes backpressure in aorta, blood is expelled from ventricle, ventricular cells shorten and blood is pushed out
- happens in bench press
13
Q
What is preload?
A
Weight that stretches muscle before it is stimulated to contract
14
Q
What happens to force as preload increases?
A
As force preload (stretch) increases, force increases up to a point then decreases
15
Q
What can preload be thought of in terms of the heart?
A
- ventricular filling
- as blood fills 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
- measures include end-diastolic volume, end-diastolic pressure and right atrial pressure
16
Q
What is afterload?
A
Weight not apparent to muscle in resting state; only encountered when muscle has started to contract
17
Q
What happens to shortening of muscle as afterload increases?
A
- as afterload increases, amount of shortening of muscle reduces
- larger the weight, the more difficulty the muscle has to shorten so amount and velocity of shortening decreases
- to change this, change the preload:
- small preload = shorter muscle lengths so less force can be produced
- large preload = longer muscle lengths so more force can be produced
18
Q
What can afterload be thought of in terms of the heart?
A
- pressure in aorta that ventricle has to overcome once it can generate enough pressure to pump blood out of 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
19
Q
What is the Frank-Starling relationship (Starling law)?
A
- as filling of the heart increased, force of ventricular muscle also increased
- law: 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
- if more blood comes into heart, heart filled more, ventricles contract more and vice versa
20
Q
What are two factors that cause the Frank-Starling relationship?
A
- changes in the number of myofilament cross bridges that interact - as you stretch muscle, you increase number of myofilament cross bridges so more myosin and actin interactions - at shorter lengths than optimal the actin filaments overlap on themselves, reducing number of cross bridges that can be made
- changes in the Ca2+ sensitivity of the myofilaments - precise mechanism unclear but two hypotheses
21
Q
What is hypothesis 1 of mechanism of changes in Ca2+ sensitivity of myofilaments?
A
- Ca2+ required for myofilament activation
- troponin C is thin filament protein that binds actin and myosin
- troponin C regulates formation of cross-bridges between actin and myosin
- at longer sarcomere lengths, the affinity of troponin C for Ca2+ is increased due to conformational change in protein
- less Ca2+ therefore required for same amount of force
22
Q
What is hypothesis 2 of mechanism of changes in Ca2+ sensitivity of myofilaments?
A
- with stretch the spacing between myosin and actin filaments (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 Ca2+
23
Q
What is stroke work?
A
- work done by heart to eject blood under pressure into aorta and pulmonary artery
- stroke work = volume of blood ejected during each stroke (SV) x pressure at which blood is ejected (P)
- stroke work = SV x P
- preload and afterload greatly influence SV
- cardiac structure greatly affects P
24
Q
What is the law of LaPlace?
A
- when the pressure within a cylinder is held constant, the tension on its walls increases with increasing radius
- wall tension = pressure in vessel x radius of vessel
- T = P x R
- incorporating wall thickness (h) amends this to:
- T = (P x R)/h
- in the heart, the RV and LV have blood of different pressure but we want tension to remain the same = we can have them have different radii
