Cardiovascular Mechanics Flashcards
What does a ventricular cell require for contraction?
External Ca2+
Outline the process of contraction in a single ventricular cell.
Electrical event (AP)
Calcium transient (amount of calcium in sarcoplasm has ^ for short period of time).
Contractile
Will the heart beat without external Ca2+?
Heart WON’T beat without external Ca2+, different to skeletal muscle which can contract.
What type of indicator is activated upon Ca2+ binding?
Fluorescent indicator activated upon Ca2+ binding, transient rises in Ca2+ concordant with contraction.
Can the hearts contractility be sustained by saline solution with bicarbonate of soda and KCL?
No
The addition of lime or a calcium salt will restore good contractility.
What are T-tubules?
Finger-like invaginations of the cell surface.
What is the length and width of ventricular cells?
Length: 100 micrometers; Width: 15 micrometers.
Dimensions of T-tubules?
200nm, T-tubules are separated by 2micrometers, intermediate between each Z-line of myofibril, transmitting surface depolarisation deep into the cell.
Proportion of myofibrils, MC and SR in single ventricular cell?
Myofibrils - 46%
MC - 36% - High proportion of MC to provide ATP for contractility (ATP for sliding filament theory).
SR - 4%
Outline the process of excitation-contraction coupling in the heart.
- L-type Ca2+ channel, upon excitation, the depolarisation is sensed by the ion channel in the cardiomyocyte, consequently this opens the channel in response to AP.
- Extracellular Ca2+ moves across concentration gradient intracellularly by diffusion.
- Minor proportion of Ca2+ activates actin filaments and directly causes contraction.
- Majority of Ca2+ binds to RyR on SR (SR Ca2+ release channel); receptor undergoes conformational change (Ligand gated); opening RyR → Efflux from SR.
- Ca2+ binds to TnC on actin filaments to stimulate shortening of sarcomere (sliding filament theory)
- Relaxation period: Ca2+ actively pumped into a stored position by Ca2+ ATPase channels of SR. Same amount of Ca2+ that came into the cell is effluxed by a Na-Ca exchange.
Does excitation-contraction coupling in heart require energy?
Doesn’t require energy; energy is transferred via the concentration gradient of Na+ to expel Ca2+ from cell.
Explain the relationship between the force production and intracellular Ca2+.
Force-Ca2+ relationship sigmoidal. Intracellular cytoplasmic Ca2+ ^ will subsequently result in a greater force exerted by the muscle.
10 micrometers intracellular concentration sufficient to produce maximum force.
How can we add Ca2+ in SR?
Sympathetic stimulation
Increased phosphorylation of some proteins and increase Ca2+ influx into cell.
What is the Length-tension relationship?
Increase in muscle length causes an increase in force.
Active force production line.
Cardiac preparation increase, muscular force increase (Tension system).
Elastic components (Elastin) stretch, passive tension is produced; cytoskeletal components of cells stretching, EPE is stored, this occurs during no shortening of the muscle → Isometric contraction.
Muscle length increases, passive force increases.
What is an isometric contraction?
Tension provided does’t cause muscular shortening; exerts pulling force on transducer.
LTR cardiac vs. skeletal muscle
Overstretch the muscle beyond the actin and myosin filament overlap will result in a decrease in force; behaviour is exhibited in skeletal muscles.
What is active and passive force?
Passive - Based on the resistance to stretch of the muscle.
Active - Dependent on sarcomere shortening, forces act in the direction of point of muscular attachment towards centre.
What is the total force?
Passive + Active
What type of muscle is less compliant?
Cardiac muscle → less compliant, and resilient to stretch in comparison to skeletal muscle, thus exerts more passive force.
What are the 2 forms of contraction the heart uses?
Isometric
Isotonic
What is isometric contraction?
Muscle fibres don’t change length but pressure increases in both ventricles.
What is isotonic contraction?
Shortening of fibre and blood is ejected from ventricles.
Examples of isometric and isotonic contractions?
Isometric - Planque,
Isotonic - Bicep curls, bench press.
What is preload?
Degree to which cardiac muscle cells are stretched from filling of the ventricles prior to contraction. Therefore, preload is a way of expressing end-diastolic volume. Increasing ventricular filling → increases EDV and cardiac muscle is stretched to a greater degree.
What is the difference between force produced with a small preload and a large preload?
Small preload - shorter muscle lengths > less force can be produced.
Large preload - longer muscle lengths > more force can be produced.
What is EDV?
End-diastolic volume → Volume of blood present in the ventricles before ventricular systole.
What factors effect EDV?
Filling time - Duration of ventricular diastole during filling.
HR - Greater the contraction rate, the shorter the filling time, thus lowers EDV and preload.
How does preload affect contractility?
Increased preload → Increases contractility
What is cardiac contractility?
Tension developed and velocity of shortening (Strength of contraction) of myocardial fibres at a given preload, and afterload.
How does sympathetic stimulation affect preload?
Increases venous return to the heart, contributes ventricular filling, EDV + preload. Atria and ventricles in diastole, majority of ventricular filling and atrial kick.
In vivo correlates of preload.
As blood fills the heart during diastole, it stretches the resting ventricular cells. This stretch (filling) determines the preload on the ventricles before ejection. Preload is dependent on venous return.
What do preload measure include?
EDV, end-diastolic pressure and right atrial pressure.
What is afterload?
Load against which left ventricle ejects blood after opening aortic valve.
What does any increase in afterload do to the amount of isotonic shortening?
Decreases the amount of isotonic shortening that occurs and decreases the velocity of shortening.
What decreases afterload?
Vasodilators and factors decreasing resistance.
What does more afterload do to the velocity of shortening?
More afterload = Less sarcomere shortening
More afterload = Decreases velocity of shortening.
What do measures of afterload include?
Diastolic arterial BP.
What does increased afterload do?
Decrease shortening + decrease velocity of shortening.
Definition of F-S relationship.
Increased diastolic fibre length increases ventricular contraction.
What is the consequence of the F-S relationship?
Ventricles pump greater SV so that, at equilibrium CO exactly balances that augmented venous return.
Name the 2 factors that are thought to have caused the Frank-Starling Relationship.
Change in the number of myofilament cross-bridges that interact.
Changes in the Ca2+ sensitivity of the myofilaments.
Explain how changes in the number of myofilament cross-bridges that interact causes the F-S relationship.
Ventricular stretching ^ contact between the myosin heads with the myosin binding sites, lattice-spacing decreases.
Decreasing myofilament lattice spacing, increasing the probability of forming strong-binding-cross-bridges; providing more force for the same amount of activating calcium.
Explain how changes in Ca2+ sensitivity of myofilaments causes the F-S relationship.
Ca2+ required for myofilament activation, troponin C (TnC), is thin filament protein that binds Ca2+, subsequently causing tropomyosin to expose myosin binding sites, regulating 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; thereby less Ca2+ is required for equivalent amount of force.
Define SW + equation.
Work done by heart to eject blood under pressure into aorta and pulmonary artery.
SW = SV x P
What factors affect SW?
SV affected by PRELOAD and AFTERLOAD
Pressure affected by CONTRACTILITY
Define the Law of Laplace + equation.
When the pressure within a cylinder is held constant, the tension on its wall increases with increasing radius.
Wall tension = Pressure in vessel x Radius of vessel
T=PR
T=PR/h
Which ventricle lower radius?
LV allowing it to generate higher pressures than the RV with similar wall stress/
