Myocardial relaxation and diastolic function

Diastole (filling)

Systole (pumping)

What are the 2 divisions of the cardiac cycle

Relaxation (active)

Myocardial stiffness/ distensibility (passive)

What are the 2 principal determinants of diastole

Lusitropy

Term referring to the relaxation property of myocytes

Myocardial relaxation

Term used to characterize rate (velocity) and extent (magnitude) of fiber lengthening

Relaxation property of myocytes

What is lusitropy

Period of cross-bridge detachment associated with active relieve of muscle tension followed by filling of the ventricles

What is myocardial relaxation

SERCA

Phospholamban

ATP (O2)

Na+ - Ca++ pump

Ca++ pump

What are the essential components of relaxation

Preload

Afterload

Prior systole

Chamber geometry

What factors impact relaxation

Increases Ca++ entry and re-uptake

Increases both contraction and relaxation

What is the effect of sympathetic stimulation on relaxation

Decreases Ca++ entry and re-uptake

Decreases both contraction and relaxation

What is the effect of parasympathetic stimulation on relaxation

SERCA controls cytosolic Ca++ concentrations

When unphosphorylated, phospholamban inhibits SERCA

This prevents re-uptake of Ca++

Prevents relaxation

What is the interaction between SERCA and PLB

When phospholamban (PLB) is unphosphorylated, it inhibits SERCA, preventing re-uptake of Ca++

Sympathetic stimulation on beta-receptors causes phosphorylation of PLB

PLB phosphorylation prevents inhibition of SERCA

SERCA pumps Ca++ back into SR, causing relaxation

How does sympathetic stimulation increase myocardial relaxation

Heart rate

What is chronotropy

Chronotropy

Fancy word for heart rate

Bathmotropy

Increased spontaneous polarization in ventricles leading to arrhythmias

Increased spontaneous polarization in ventricles leading to arrhythmias

What is bathmotropy

Dromotropy

Conduction velocity

Conduction velocity

What is dromotropy

Inotropy

Contraction property of myocytes

Contraction property of myocytes

What is inotropy

Contraction nearly completed

Ca++ detaches from binding site

Na+-Ca++ exchanger expels some Ca++ out of cell

SERCA pumps most into SR where it is bound to calsequestrin

Some Ca++ temporarily stored in mitochondria

Some modulating proteins bind remaining Ca++

Myocytes relax and lengthen

Heart recoils and untwists from stored systolic forces

Active blood suction and passive filling (following LA-LV pressure gradient) occur. Ventricle starts filling

What is the process of cardiomyocyte relaxation

Adequate filling of ventricles at rest and during exercise without pathologic elevation of filling pressures

What is considered normal diastolic function

Diastolic function relates relaxation and passive tissue properties to preload

Lusitropy= rate and extent of cell lengthening (relaxation) at 0 load- inherent property of the muscle

Diastolic function= chamber filling

What is the difference between lusitropy and diastolic function

Isovolumic relaxation

Rapid filling

Slow filling

Atrial contraction

What are the phases of diastole

Diastole. Period of time from aortic valve closure to mitral valve opening

All valves closed

Atrium and ventricle are relaxed

What is isovolumic relaxation

Rapid filling

-AV valves are open. Semilunars closed

-both atria and ventricles relaxed

-passive inflow into ventricles

Slow filling: diastasis

-mitral valve partially open

What are the filling phases of diastole

Diastole

-AV valves are open

-semilunars closed

-atria contract to push blood into ventricles before AV closures (20% of filling volume in normal conditions)

What is atrial contraction

LA fills during ventricular systole

Active LV relaxation= dec LVP

LVP < LAP: mitral opens. Blood flows LA-> LV

LAP falls, LVP increases: Early filling wave (E). 80% of filling volume

LVP inc, filling dec but continues in mid-diastole (diastasis). LA functions as a channel (conduit)

Atrial kick at end-diastole. Inc LA pressure and late filling wave (A). 20% of filling volume (up to 60% in exercise)

What are the ventricular fluid dynamics during diastole

Suction (active)

Untwisting (passive)

LA/LV pressure differences (passive

Relaxation (passive)

What factors influence early diastole

Atrial kick (active)

What factors influence late diastole

Function properties: active relaxation

Tissue properties: passive compliance/ stiffness

What are the 2 main mechanical characteristics that determine diastole

Rate of fall of pressure (dP/dtmin) during isovolumic relaxation (mmHg/s)

Pressure-volume loops (mmHg/mL)- determine end-diastolic P-V relationship= variable of chamber stiffness

What are the catheter-based (invasive) variables of diastolic function

Plot between diastolic pressure and diastolic volume of the LV over the course of diastole

Slope of a tangent at any end-diastolic volume shows overall LV compliance

If the myocardium is compliant, the curve is flat (good)

If myocardium is not compliant, curve is steep (bad)

-if the wall is stiff and is still bringing in the same amount of blood, then the pressure is higher due to the decreased size of the lumen

How is compliance of the myocardium measured via catheter-based (invasive) techniques

Relaxation: isovolumic relaxation time (ms)

Filling: ratio of early (E) to late (A) filling velocities

What are the echocardiography-based (non-invasive) variables of diastolic function

Increased preload (end-diastolic fiber stretch) improves diastolic function (within physiological limits)

Inc volume= inc preload

How does preload impact diastolic function

Increased HR improves relaxation and ventricular suction BUT can decrease filling time and coronary perfusion

Extremely high HR (over 160 bpm) makes relaxation worse

-filling reduced. No time for relaxation to allow filling

-constant firing means Ca++ is not pumped away and overloads the muscle. Poor relaxation= muscle becomes stiff (decreased compliance)

How does heart rate impact diastolic function