Cardiac Physiology: Relaxation and Diastolic Function

The cardiac cycle is divided into two parts:

1.) diastole

2.) systole

diastole

filling of the ventricles and relaxation of the heart

Two principal features determining diastole:

1.) active processes

2.) passive processes

Active process determinining diastole

relaxation

Passive processes detemrining diastole

myocardial stiffness and distensibility

Myocardial relaxation is aka...

lusitropy

lusitropy

characteristizes the rate (velocity) and extent (magnitide) of fiber lengthening

Relaxation relates to period of cross bridge _________

detachment

Cross bridge detachment will relieve muscle ________

tension

Relaxation is followed by...

fillling of the ventricles

Five essential components of relaxation:

1.) SERCA

2.) phospholamban

3.) ATP

4.) Na/Ca pup

5.) Ca pump

SERCA

enzyme that pumps calcium back into SR following contraction

SERCA is inhibited by...

phospholamban

What removes phospholamban from SERCA?

phosphorylation by sympathetic activation

During a power stroke, what causes myosin to detach from actin?

removal of calcium from the tropomyosin binding site on actin

Main protein responsible for helping to remove Ca from actin

SERCA

Four other ways Ca is removed from the tropomyosin binding site:

1.) Na/Ca pump

2.) Ca pump

3.) mitochondiral storage

4.) modulating proteins

The Na/Ca pump and Ca pump move Ca where?

outside of the myocardial cell into the extracellular space

Relaxation is an ________ process

active (requires ATP)

Four things that affect relaxation:

1.) preload

2.) afterload

3.) prior systole

4.) chamber geometry

Relaxation begins when....

contraction is nearly complete

Relaxation ends after...

filling of the ventricles

Steps of cardiomyocyte relaxation:

1.) begins when contraction is complete

2.) Ca detaches from troponin C binding sites

3.) Free Ca is removed through several mechanisms including:

-SERCA pumping into the SR

-Na/Ca and Ca pumps expeling Ca out of cell

-Ca being stored in mitochondria

-modulating proteins binding to remaining Ca

4.) After Ca is removed, myocytes lengthen and passive filling begins

Two ways myocardial relaxation is controlled:

1.) Intracellular Ca concentration

2.) Autonomic control

Increase in sympathetic activation will _______ relaxation

Increase in parasympathetic ctivation will _______ relaxation

increase

decrease

Where are B1 receptors mostly found?

ventricles, but found everywhere in the heart

The autonomic signaling molecule for B1 receptor is...

norepinephrine and epinephrie (sympathetic)

Where are Muscarinic M2 receptors mostly found?

SA node, AV node, and ventricles

The autonomic signaling molecule for Muscarinic M2 receptors are...

acetylcholine (parasympathetic)

How does sympathetic signaling increase relaxation?

1.) norepinephrine or epinephrine bind to B1 receptor

2.) through a cascade of reactions, phospholamban is phosphorylated

3.) phophorylation of phospholamban frees SERCA protein

4.) SERCA protein helps pump Ca from the cytosol into the sarcoplasmic reticulum

5.) less Ca in cytosol = less Ca binding to actin = myosin cannot attach and relaxation occurs

The sympathetic nervous system will _________ Ca re-uptake, leading to ________ relaxation

The parasympathetic nervous sytem will _________ Ca re-uptake, leading to ________ relaxation

increase; faster

decrease; slower

Inotropy

rate of contraction

Lusitropy

rate of relaxation

Chronotropy

rate of heart rate

Dromotropy

rate of conduction velocity

Bathmotropy

Defines the excitability of cardiac muscle

Diastolic function

relates relaxation and passive tissue properties to preload (volume)

Normal diastolic function allows for ________ of ventricles without _________ in pressure

filling; increase

Diastolic function is not the same as...

lusitropy

Difference betwen diastolic function and lusitropy

diastolic function: overall process of ventricular filling

lusitropy: rate (velocity) and extent (magnitide) of fiber lengthening

Diastole is a _________ process

phasic

Two phases of diastole:

1. isovolumetric relaxation

2. filling phase

The isovolumetric relaxation phase of diastole immediately follows...

ventricular ejection

isovolumetric relaxation phase of diastole

All valves are closed and pressure in the ventricle decreases due to relaxation of myocytes

During isovolumetric relaxation, there is no change in ________ but _________ decreases significantly

volume; pressure

The isovolumetric relaxation phase is the period from all valves ________ to the ________ valve ________

closing; mitral; opening

cardiac cycle: filling

Mitral valve opens and blood rushes into the left ventricle from the left atrium

What causes ventricular filling to occur?

pressure in the left ventricle becomes less than that of the left atria

Two parts of ventricular filling

1.) passive

2.) active

passive filling

period during diastole in which blood flows through the atria into the ventricles under relatively low pressure

During passive filling, the atria are not __________

contracting

The passive filling phase can be further broken down into...

a rapid filling and slow filling phase

Rapid filling phase of passive filling

the mitral valve is completely open and blood rushes in

Slow filling phase of passive filling

The mitral valve begins to close as pressure in the ventricle increases, slowing blood flow into the ventricle

active filling

atria contracts and squeezes remaining blood into the ventricles

What causes active filling to occur?

SA node firing

Active filling is aka....

"atrial kick"

Early diastolic filling provides _____% of left ventricle filling volume, and the "atrial kick" provides ___%

80%; 20%

When will the atrial kick contribute more towards left ventricle filling volume?

during exercise; increases to 60%

Diastole can be measured through what variable?

filling

Two ways to measure diastolic function:

1.) catheter based (invasive)

2.) echogardiography (non-invasive)

catheter based (invasive) method measures two things:

1.) rate of fall of pressure during isovolumetric relaxation

2.) pressure volume loops

rate of fall of pressure during isovolumetric relaxation

measuring the rate of fall of pressure from the closure of all of the valves to when the mitral valve opens

pressure volume loops

measures compliance; plots the relationship of pressure and volume in the heart during one cardiac cycle

compliance

how easily the ventricle expands (fills) when blood enters it; aka is it able to stretch or is it stiff

Pressure volume loops measure ventricular _________ diastolic properties

passive (stiffness/compliance)

The higher compliance is, the _______ the pressure loop curve

flatter (this is ideal)

The lower compliance is, the _______ the pressure loop curve

steeper (this is bad)

What does echocardiography measure (2)?:

1.) relaxation

2.) filling

How is relaxation measured using echocardiography?

the isovolumetric relaxation time is measured

How is filling measured using echocardiography?

the ratio of early to late filling velocites is calculated

*velocity is measured using doppler function

Increased ________ and ________ will improve diastolic function

preload; heart rate

*within physiological limits

How does increased preload improve diastolic function?

the more the fibers are able to stretch, the more the ventricles are able to fill, improving relaxation

How does increased heart rate improve diastolic function?

increasing the heart rate will enhance lusitropy; there is faster Ca reuptake, faster relaxation, earlier valve opening, and stronger diastolic function

What happens if heart rate increases too much beyond physiological limits?

The Ca pumps cannot keep up, which leads to stiffness and decreased compliance; the heart fibers cannot stretch and fill with blood

Which statement about myocardial relaxation is CORRECT?

a. It is a passive process related to the early diastolic LA-LV pressure difference.

b. It does improve with increased Ca 2+ binding to the tropomyosin complex.

c. It is facilitated by binding of phospholamban to SERCA.

d. It gets faster and stronger with parasympathetic activation.

e. It is a process mainly confined to the isovolumic period in early diastole

e. It is a process mainly confined to the isovolumic period in early diastole

Which of the following sequence of events during cardiac excitation-contraction-relaxation is CORRECT?

1... Ca 2+ binding to cardiac troponin C

2... Ca 2+ entry via the L-type Ca 2+ channel

3... Power stroke

4... Ca 2+ extrusion out of the cytoplasm via the Ca 2+ pump

5... Temporary Ca 2+ storage in the mitochondria

6... Electrical cardiomyocyte activation

7... Ca 2+ triggered Ca 2+ release

8... Ca 2+ flux into the sarcoendoplasmatic reticulum via SERCA

a. 6-->7-->2-->5-->8-->1-->3-->4

b. 6-->2-->7-->1-->3-->8-->4-->5

c. 3-->6-->5-->8-->2-->7-->4-->1

d. 1-->2-->3-->4-->5-->6-->7-->8

e. 8-->7-->6-->5-->4-->3-->2-->1

b. 6-->2-->7-->1-->3-->8-->4-->5

All of the statements about ventricular diastolic function are correct, EXCEPT?

a. Diastolic function is an overarching term to describe ventricular filling.

b. Diastolic function can conceptionally be divided into 4 phases occurring in the following sequence: Isovolumic contraction, early filling, late filling, and finally diastasis.

c. Rapid ventricular filling occurs in early diastole and is caused by myocardial relaxation associated with suction of blood into the ventricle reducing LV pressure and thus the early diastolic LV-LA pressure gradient.

d. Normal diastolic function allows adequate filling of the ventricles withouta pathologic elevation of filling pressure.

e. Stiffness (or its reciprocal, compliance) describes the passive diastolic properties of the myocardium (ventricle). The stiffer, the worse is diastolic filling

b. Diastolic function can conceptionally be divided into 4 phases occurring in the following sequence: Isovolumic contraction, early filling, late filling, and finally diastasis.

A cat with severe, idiopathic thickening of the LV walls and a heart rate of 260 bpm (N: 120-220) is diagnosed with hypertrophic cardiomyopathy in your practice via cardiac ultrasound (we will talk about this common feline condition later in the course). Which of the following statements regarding LV diastolic function in this cat is NOT correct?

a. LV compliance will be decreased and thus LV filling reduced.

b. Relaxation of the LV will be abnormal due to increased myocardial mass.

c. High heart rate will make LV filling worse.

d. LV stiffness will be increased affecting LV diastolic (filling)properties.

e. LV stroke volume will be increased due to increased heart rate and better relaxation and thus, better filling, of this thickened heart.

e. LV stroke volume will be increased due to increased heart rate and better relaxation and thus, better filling, of this thickened heart.