CS 2015
Cardiac Output as HR·SV and Introduction to Starling's Law
Christian StrickerAssociate Professor for Systems Physiology
ANUMS/JCSMR - ANU
[email protected] 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.
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• 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
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• 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)
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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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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
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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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“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↓).
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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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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
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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• 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.
Mod
ified
from
Sch
mid
t & T
hew
s, 1
977
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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