Regulation of Cardiac Contractility

Length-Tension Relationship

• If there is too much overlap there is not enough space for the sarcomere to contract

  • Minimal force tension is produce and therefore minimal tension

• If sarcomere stretch too much, there won't be any overlap and myosin won't be able to bind to actin

  • No tension is produce, no force produce

  • Sarcomere will break

• Optimal lengh is at 2.4 micrometer where there is some/minimal overlap which optimizes the most walkable distance for myosin

  • Produces the more forceful contraction

• Normal resting sarcomere length is 2.2 micrometer

• The shape is also due to calcium sensitivity

How does stretching the Cardiac Sarcromere produce more force (How does Frank-Starling law make sense)

• Stretching a sarcomere will increase calcium sensitivity

  • Less Ca2+ is needed to produce force

  • TnC conformation changes and increase TnC Ca2+ affinity

• As the sarcromere is stretched, Titin decreases the space between myofilaments

  • Brings them into closer proximity, increase probability of cross bridge at a given level of calcium

  • Increase the cross-bdrige formation

• Stretch actvated Ca2+ channels are activated and SR Ca2+ release

  • More calcium released = higher force production

Cardiac vs Skeletal LT relaitonship

• Cardiac

  • Titin increase the sarcomere stiffness

    • Will increase resistance to passive stretch and increase passive tension/force

    • Decrease active force generation

  • Skeletal

    • Has more distensible non-contractile components (different isoform of titin)

    • Active tension regulated by myosin filament overlap

      • Can generate higher active force at longer lengths

      • Generates less passive force

      • Has different length at which passive force is generated

Frank Starling Mechanism

All blood returned to the heart must be ejected out. Increase in EDV = Increase in Force (systolic pressure

x axis: EDV proportional to length y axis: Systolic or diastolic pressure is proportional to force

Diastole

• As heart is being passively filled with blood it causes the stretching of ventricles

  • More stretched = higher force of contraction

  • Diastolic curve is equivalent to passive tension

  • EDV is proportional to sarcomere length

  • Increasing ventricular filling will increase force of contraction

Systole

• Higher amount of blood in the volume, higher the force produce during a heart contraction is

• Hearts pumps all blood returned to the heart

 

Factors that increase EDV

• Higher venous return (exercise and venous constriction)

•  lower heart rate (more filling time)

Preload

• the strength of the ventricular myocytes at the end of diastole just before contraction

  •  is proportional to sarcomere length which is proportional to EDV

  • Higher preload means greater EDV

  • As preload increases the heart contracts more forcefully and ejects more blood

Afterload

•  resistance the ventricles must overcome to eject blood

  • Approximated by aortic pressure

  • It is the "load" or pressure the heart must work against to push blood into circulation, to open the semilunar valve

  • The force required to open semilunar valve, we are working against blood int eh aorta

  • AL is proportional to blood pressure

    • If person has hypertension the heart must work harder to eject blood

  •  different between max tension and rest

 

Preload and Afterload together

• Higher preload allows heart to better tolerate a given afterload

  • Start at a longer length to generate greater active force

  • Increase pre load, large SV, greater cardiac output, can raise arterial pressure and increase afterload

Isometric phase

Length remains the same but tension/force increases

Isotonic phase

Force is constant but muscle shortens

Increase in Preload

Increase force generation

Increase in afterload

• Decrease velocity of contraction

  • Takes a longer time to build tension

• Increase isometric contraction

  • Isovolumetic contraction is longer when we increase AL

  • Muscle is producing tension/pressure but no blood has been ejected yet

• Decrease time of shortening

  • Due to the long time in isometric phase it does not have enough time to shorten all the way until it must refill again

  • It will decrease the length to which it shortens

Force Velocity graph

 

• Decrease in preload = decrease force generation

  • Graph shift left

• Increase in pre load, = increase force generation

  • Graph shifts right

• Muscle contraction can be forceful or fast, not both

Types of myosin isoforms and Force velocity graph

• alphas the fastest rate of cross bridge cycling

  • Higher velocity of muscle contraction

  • "shorter life span"

Beta-beta myosin

• Decrease force production for a given velocity

  • Most efficient "longer lifespan"

Max Velocity and Max force Factors

Max force is independent of the rate of cross-bridge

cycle

Max velocity is adapted to match max HR

• Higher velocity allows for faster Hr

• determined by rate of cross-bridge cycling