the australian national university

CS 2015

Cardiac Output as HR·SV and Introduction to Starling's Law

Christian StrickerAssociate Professor for Systems Physiology

ANUMS/JCSMR - ANUChristian.Stricker@anu.edu.au

http://stricker.jcsmr.anu.edu.au/Cardiac_output.pptx

THE AUSTRALIAN NATIONAL UNIVERSITY

CS 2015

CS 2015

AimsAt the end of this lecture students should be able to

• estimate CO and EF;• outline how CO is determined by HR;• define the terms preload and afterload;• explain the functional properties of the pump in regard to

– contractility, – fibre thickness, – relationship between force production and sarcomere length,

and– relationship between shortening velocity and force production;

• outline how pre- and afterload affect CO;• discuss how Starling’s law affects CO; and• illustrate how afterload can influence preload.

CS 2015

• Measures of cardiac output (stroke volume, heart rate, cardiac index, ejection fraction)

• Heart rate and cardiac output• Preload

– Contractility (Starling’s law)– Fibre thickness

• Afterload– Ventricle size and wall tension

• How afterload can affect preload

Contents

CS 2015

• Cardiac output = ejected vol. per time [min-1]. Example: Heart rate (HR) = 70 min-1 (bpm)Stroke volume (SV) = 80 mL

• Cardiac index (CI) = CO normalised per unit body surface area (BSA, normally 1.6 m2). Example:

• Ejection fraction = ratio of SV to end-diastolic volume (EDV, ~120 ml) in %. Typically > 55%. Example:

Cardiac Output (CO)

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Factors Determining CO

• Heart rate (HR): Electrical properties• Stroke volume (SV):

– Force of contraction: Muscular properties• End-diastolic fibre length (Starling’s law):

pre-“stress”, pre-“tension”, preload, compliance

• Contractility: force generation of cardiac fibre• Trophic state of cardiac fibre (thick, thin)

– “Afterload”: Circulatory properties• Ventricular radius (Laplace’ law)• Systolic pressure (Resistance)

CS 2015

Factors Determining CO• Heart rate (HR): Electrical properties• Stroke volume (SV):

– Force of contraction: Muscular properties• End-diastolic fibre length (Starling’s law):

pre-“stress”, pre-“tension”, preload, compliance

• Contractility: force generation of cardiac fibre• Trophic state of cardiac fibre (thick, thin)

– “Afterload”: Circulatory properties• Ventricular radius (Laplace’ law)• Systolic pressure (Resistance)

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HR, SV and CO

• HR determined by autonomic innervation:– Sympathetic: HR↑– Parasympathetic: HR↓

• SV & HR linearly related.– Mechanism: pulse rate↑ →

ventricular filling↓.

• CO maximal at ~130 bpm; drops with higher HR.– Explanation: above optimal

frequency, HR↑ insufficient to compensate for SV↓.

Corrected from Patton et al., 1989

CS 2015

Factors Determining CO• Heart rate (HR): Electrical properties• Stroke volume (SV):

– Force of contraction: Muscular properties• End-diastolic fibre length (Starling’s law):

pre-“stress”, pre-“tension”, preload, compliance

• Contractility: force generation of cardiac fibre• Trophic state of cardiac fibre (thick, thin)

– “Afterload”: Circulatory properties• Ventricular radius (Laplace’ law)• Systolic pressure (Resistance)

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“Preload”

Preload = pressure (or volume) at end of diastole → sets end-diastolic ventricular fibre length.

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Preload and SV (Frank-Starling)

O. Frank 1895 (frog heart); E.H. Starling 1914 (dog)

• End-diastolic filling pressure (~15 torr) expands ventricle to particular volume: sets cardiac fibre length.

• Within a certain limit, SV↑ for larger volumes/pressures.• Put simply: Bigger preload → larger SV (within about a ~2

fold range): homeostatic mechanism.

Pat

ton

et a

l., 1

989

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How Preload Determines SV

• Steep relationship between force/pressure production and sarcomere length (see also muscle physiology).

• Increased cardiac force translates into increased SV: force ↑ →

effective load↓ → shortening vel↑ → ejection↑ → SV↑ (see below).• Homeostatic mechanism to match RV with LV output.

– If -1% LV mismatch, within 2 h, total blood volume in pulmonary circulation → pulmonary oedema.

Pat

ton

et a

l., 1

989

CS 2015

Preload Determinant: Compliance

• If ventricular filling causes a small change in ventricular pressure, then the ventricle is compliant - otherwise stiff:

+ Dilated cardiomyopathy– Impaired ventricular muscle relaxation (myocardial hypertrophy, myopathy).– Fibrosis (for example after lots of small local infarcts).

• Decreased compliance results in SV↓ (filling↓).

CS 2015

Factors Determining CO• Heart rate (HR): Electrical properties• Stroke volume (SV):

– Force of contraction: Muscular properties• End-diastolic fibre length (Starling’s law):

pre-“stress”, pre-“tension”, preload, compliance

• Contractility: force generation of cardiac fibre• Trophic state of cardiac fibre (thick, thin)

– “Afterload”: Circulatory properties• Ventricular radius (Laplace’ law)• Systolic pressure (Resistance)

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Patton et al., 1989

Modulation of Contractility: Ca2+

• Contractility depends on– [Ca2+]i reached for EC-coupling:

high [Ca2+]i → larger isometric

force (Sarnoff & Mitchell, 1961).– Fibre length at beginning of

contraction: stretched fibres → larger force.

– Sympathetic activity (see earlier – no parasympathetic effect!).

• Also dependent on HR and afterload.

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Modulation of Contractility: Drugs• NA (diffusely released on myocytes):

contractility↑– L-type Ca2+ channels,– Cytosolic Ca2+ concentration,– Store refilling via SERCA/PLB, and– Contractile proteins (troponin 1).

• Hormones and drugs+ Digitalis, β-adrenomimetics

(isoproterenol), glucagon– Anaesthetics, toxins

• Disease states:– Alterations in electrolytes, acid-base

balance– Coronary artery disease / hypoxia– Myocarditis– Bacterial endotoxaemia

Rhoades & Tanner, 2003

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Factors Determining CO• Heart rate (HR): Electrical properties• Stroke volume (SV):

– Force of contraction: Muscular properties• End-diastolic fibre length (Starling’s law):

pre-“stress”, pre-“tension”, preload, compliance

• Contractility: force generation of cardiac fibre• Trophic state of cardiac fibre (thick, thin)

– “Afterload”: Circulatory properties• Ventricular radius (Laplace’ law)• Systolic pressure (Resistance)

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Contractility and Fibre Thickness

• Force increases with hypertrophy (athletes).– Mechanism: more contractile proteins (myofilaments) per myocyte produce

bigger force.– Changes reversible (can be exploited after infarction).

• In hypertrophic cardiomyopathy, changes can lead to force production↓.– Ventricular remodelling is under β-adrenergic control.

CS 2015

Factors Determining CO• Heart rate (HR): Electrical properties• Stroke volume (SV):

– Force of contraction: Muscular properties• End-diastolic fibre length (Starling’s law):

pre-“stress”, pre-“tension”, preload, compliance

• Contractility: force generation of cardiac fibre• Trophic state of cardiac fibre (thick, thin)

– “Afterload”: Circulatory properties• Systolic pressure (Resistance)• Ventricular radius / volume (Laplace’ law)

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“Afterload”

Afterload = pressure (or volume) at end of systole.

– End-systolic pressure/volume– ≠ Psyst

– ≠ Pdiast

– ~ average pressure (MAP, see later) against which ventricle must contract to eject blood into aorta (“load” given by total peripheral resistance, TPR).

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Systolic Pressure & Afterload

• End-systolic pressure at aortic valve closure (>100 torr).• Put simply: Afterload↑ → SV↓ (flow velocity during ejection↓).• Afterload depends on aortic elasticity (later).

Pat

ton

et a

l., 1

989

CS 2015

How Afterload Determines SV

• Shortening velocity – force/afterload - relationship (see muscle).

• Afterload↑ decreases shortening velocity of cardiac fibres → smaller SV ejected; i.e. SV↓.

Patton et al., 1989

CS 2015

Factors Determining CO• Heart rate (HR): Electrical properties• Stroke volume (SV):

– Force of contraction: Muscular properties• End-diastolic fibre length (Starling’s law):

pre-“stress”, pre-“tension”, preload, compliance

• Contractility: force generation of cardiac fibre• Trophic state of cardiac fibre (thick, thin)

– “Afterload”: Circulatory properties• Systolic pressure (Resistance)• Ventricular radius / volume (Laplace’ law)

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Determinants of Afterload

• Laplace’ law: T ~ ri (Tension force proportional to radius).

• For same afterload and myocardial thickness, a small ventricle/volume requires less tension than a big one; i.e.

a large ventricle/volume requires more force to contract. • Clinical implications in dilated heart failure.

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Pre- and Afterload Interactions

• Shortening velocity of fibre↓ → SV↓ → atrial filling pressure↑: afterload↑ → preload↑.

• Important implications in heart failure.

Pat

ton

et a

l., 1

989

CS 2015

Take-Home Messages• SV decreases linearly with HR.• CO is determined by SV and HR.

– HR can be modulated by sympathetic and parasympathetic influences.

– SV can be increased by• preload ↑ (end-diastolic filling pressure - Starling),• contractility ↑ (sympathomimetics, digitalis, etc.),• fibre thickness ↑, and• afterload ↓ (Psyst, ultimately Rperiph).

• A large ventricle requires more tension force.• Ultimately, afterload↑ causes preload↑.

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MCQ

Which of the following statements best describes the increased cardiac output that occurs with increased sympathetic stimulation of the heart?

a) Decreased heart rate and increased contractility

b) Decreased diastolic filling time and increased heart rate

c) Increased contractility and increased heart rate

d) Decreased ventricular relaxation and increased ejection fraction

e) Increased ventricular relaxation and decreased ejection fraction

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That’s it folks…

CS 2015

MCQ

Which of the following statements best describes the increased cardiac output that occurs with increased sympathetic stimulation of the heart?

a) Decreased heart rate and increased contractility

b) Decreased diastolic filling time and increased heart rate

c) Increased contractility and increased heart rate

d) Decreased ventricular relaxation and increased ejection fraction

e) Increased ventricular relaxation and decreased ejection fraction