Diastolic function of the heart, Phases, Enddiastolic volume &

pressure, Factors affecting

Diastole

• time period during which the myocardium loses its ability to generate force and shorten and returns to an unstressed length and force

• Begins with the closure of aortic/pulmonic valves

• 2/3rd of cardiac cycle

• Total duration : 0.53 sec at HR of 72/min

• Active & passive components

Active Relaxation• occurs in a series of energy-

consuming steps

• Release of calcium from troponin C,

• detachment of the actin-myosincross-bridge,

• phosphorylation of phospholamban,

• Sarcoplasmic reticulum calcium ATPase–induced calcium sequestration into the sarcoplasmic reticulum,

• sodium/calcium exchanger–induced extrusion of calcium from the cytoplasm,

• extension of the sarcomere to its rest length

Phospholambanmembrane proteinthemuscle

. Phospholambancontractility and modulates SR Ca2+ sequestration by inhibiting the SR Ca2+(SERCA) in its dephosphorylated state. Upon phosphorylation, which is mediated through betaeffect of SERCA is relieved. This review summarizes recent advances that have been made towards understanding the modulation of SR Ca2+sequestration by generation and characterization of genetically altered animal models. It also discusses the role of and recent attempts to restore SR function in experimentally induced and human heart failure, which may be translated into future therapeutic approaches in the treatment of this disease.

Phases of diastole

• Protodiastole

• Isovolumic relaxation

• Rapid filling

• Diastasis

• Atrial kick

• The isovolumic relaxation phase is energy dependent

• does not contribute to ventricular filling

• Auxotonic relaxation phases (phases 2 through 4), ventricular filling occurs against pressure gradient (passive)

• Encompasses a period during which the myocardium is unable to generate force and filling of the ventricular chambers takes place

Protodiastole

– Once the ventricular muscle is fully contracted, the already falling ventricular pressures drop more rapidly

– 0.04sec

– ends when the momentum of the ejected blood is overcome and the aortic and pulmonary valves close

Isovolumic relaxation

– from closure of the aortic valve to opening of the mitral valve

– 0.03-0.06sec

– Energy dependent

– Left ventricular volume constant (no filling)

– left ventricularpressure decreases

Rapid filling stage

– Starts with opening of mitral valve

– transmitral pressure gradient drives LV filling

– 70-80% of filling

– Early filling correlates with the

E-wave of transmitral flow doppler

Diastasis

– period of low flow in mid-diastole

– Lt.Atrial Pressure=Lt.Ventricular Pressure

– Little oR NO flow <5%

– correlates with the interval between

E- and the A-wave of the transmitral

Doppler signal

Atrial kick

– Atrial contraction leads to late rapid filling

– Contributes 15-25% of LVEDV

– correlates with the A-wave of the mitral inflow signal

– Becomes important in AF, high ventricular rate, stiff ventricle

Diastolic time

Factors affecting diastolic function

• passive chamber stiffness (remodelling)

• elastic recoil of the ventricle

• the diastolic interaction between the two ventricular chambers

• systolic volume load

• atrial properties (rhythm,contractn)

• Drugs (catecholamines)

Effects of beta stimulation

• Increases both ionotropy and lusitropy(relaxation)

• Ionotropic state regulated by Ca concentration in cytoplasm, increased by beta stimulation (cAMP mediated)

• Lusitropy governed by phosphorylation of phospholamban and Troponin I, which is partially regulated by beta stimulation.

Invasive assessment

• Done by measurement of LV pressure with a high-fidelity micromanometer catheter

• Calculates the peak instantaneous rate of LV pressure decline, peak dP/dt, and the time constant

Non-invasive Assessment

Via Doppler echocardiographyFlow velocities are measured acrossthe mitral valve during diastole

End-diastolic Volume &

Pressure

End Diastolic Volume (EDV)Volume at the end of diastole (end of ventricular filling). In

a healthy heart this is directly proportional to venous

return

End Systolic Volume (ESV)Volume at the end of systole end of ventricular

contraction

Stroke Volume (SV) = EDV - ESV

Ejection Fraction (EF) = SV/EDV

Left Ventricular Volumes - Definitions

Left ventricular norm for EF at Rest: approximately 62%

Left Ventricular norms for Max Exercise: approximately 80%

End-diastolic volume

• Normally 110-120 ml can increase to 180 ml

Preload

• The initial length of the cardiac muscle fibrebefore contraction begins

• can be equated to the end-diastolic volume

• Clinically equated to the CVP when studying the RV or the PAOP when studying the LV

Starlings Law of the Heart and Contractility

SV

(left ventricular performance)

Preload

(venous return or EDV)

u Contractility

Normal

Contractility

d Contractility

(heart failure)

Preload X

SV at Preload X - u contractility

SV at Preload X – Normal cont.

SV at Preload X - d contractility

Starling’s Law:

The greater the EDV (blood going in the heart), the more blood comes out of the heart

The State of Myocardial

Contractility determines the

amount of blood (SV) that comes

out of the heart at a given preload

Factors affecting preload

• Venous return

• Blood volume

• Posture

• Intra-thoracic pressure

• Pericardial pressure

• Venous tone

• Heart rate & rhythm

Left

Ventricular

Pressure

(mmHg)

Volume

(ml)

Aortic Valve Closes

ESV

ESP

Mitral Valve Closes

EDV

EDP

Mitral Valve Opens

Ventricular Filling Begins

Aortic Valve Opens

120

6

40 140

Left Ventricular Pressure Volume Loop

Isovolumic

contraction

SV

Slope of dashed line:

ventricular contractility

Left

Ventricular

Pressure

(mmHg)

Volume

(ml)

120

6

40 140

Effects of an Increase in Preload on

Left Ventricular Pressure Volume Loop

u EDV

u EDP

u Ejection Pressure

u SV

Left

Ventricular

Pressure

(mmHg)

Volume

(ml)

120

6

40 140

Effects of an Increase in Afterload on Left

Ventricular Pressure Volume Loop

u ESV

u ESP

d SV

Diastolic dysfunction

Diastolic heart failure

• Heart failure accompanied by predominant or isolated abnormality in diastolic function, this clinical syndrome is called.

• symptoms and signs of heart failure, a preserved ejection fraction (EF), and abnormal diastolic function

Diastolic failure

• predominantly occurs in patients over the age of 65 and

• for unclear reasons is more common in women

• Hypertension the most common underlyingetiology. Other risk factors include diabetes mellitus, obesity, and bilateral renal artery stenosis

• Diastolic failure may also appear in elderly patients without any known predisposing

• factors, possibly as an exaggeration of the normal stiffening of the heart with age,

Diastolic failure criteria

• European society of cardiology

1. Signs/symptoms of CHF

2. Normal ?EF

3. Evidence of abnormal LV relaxation,filling,distensibility or stiffness

Left ventricular hypertrophy with and without dilation, viewed in transverse heartsections. Compared with a normal heart (center), the pressure-hypertrophied hearts (left) have increased mass and a thick left ventricular wall, while the hypertrophied,dilated heart (right) has increased mass and a normal wall thickness

normal

pressure-hypertrophied

Volume hypertrophied,dilated

• Textbook of physiology Guyton & Hall

• Ganong’s review of med. Physiology

• Miller’s anesthesia 7th edn

• Clinical anesthesiology Morgan & mikhail

• http://123sonography.com/node/939

• http://circ.ahajournals.org/content/105/11/1387.full

• http://www.aafp.org/afp/2006/0301/p841.html