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Nabavian, O.; M.D.

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10/25/2012
CARDIAC
PHYSIOLOGY
Miller’s Anesthesia
Chapter 16
Nabavian, O.; M.D.
Assistant Professor of Anesthesiology
TUMS
Vali-Asr Hospital

Nabavian, O.; M.D.

10/25/2012
 There

is difference between :
“ Intact heart” &
“ Isolated” heart muscle
Flash player Active-X
Macro’s enabled

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Ventricular structure

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Cardiac Vocabulary
 Preload: 

Preload is the muscle length prior
to contractility, and it is dependent of
ventricular filling (or end diastolic volume…
EDV) 

 The

most important determining factor for
preload is venous return.

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PReLOAD

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Cardiac Vocabulary
 Afterload:

is the tension (or the arterial
pressure) against which the ventricle must
contract.
 If arterial pressure increases, afterload also
increases.
 Afterload

for the left ventricle is determined by
aortic pressure.

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Afterload

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Law of Laplace




σ= P*R/2h
h = wall thickness

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Heart Rate and
Force-Frequency Relationship
 an

increase in the frequency of
stimulation induces an increase in the
force of contraction.
 This relationship is termed the “treppe”
phenomenon or
the force-frequency relationship

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Nabavian, O.; M.D.

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 EF=(

LVEDV-LVESV)/LVEDV

 Stroke

Nabavian, O.; M.D.

(External) work=SV * P

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Cardiac work

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External

work is expended to eject
blood under pressure, whereas
internal work is expended within
the ventricle to change the shape of
the heart and prepare it for
ejection.

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Diastolic Function
 (1)

Isovolumic relaxation
 (2) the rapid filling phase (80%)
 (3) slow filling, or diastasis;5%
 (4) final filling during atrial systole.
15%

 The

isovolumic relaxation phase is
energy dependent

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Assessing diastolic function
 (-dP/dt)
 Aortic

closing–mitral opening interval
 the isovolumic relaxation time
 peak rate of LV wall thinning as
determined by echocardiography

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CO=

SV * HR
Cardiac output in a living organism
can be measured with the
“Fick principle”
The Fick principle is based on the
concept of

conservation of mass

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Fick’s Principle
q1 =

× CpaO2

q3 =

× CpvO2

Because q1 + q2 = q3 ,
× (CpaO2 ) + q2 =

×(CpvO2

q2 =

× (CpvO2 ) −

× (CpaO2

q2 =

×(CpvO2 − CpaO2 )
= q2 /(CpvO2 − CpaO2 )

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Nabavian, O.; M.D.

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Cellular Cardiac Physiology
Cellular

anatomy:

Cardiac

muscle tissue
 Conduction tissue
 Extracellular connective tissue

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Sarcoplasmic Reticulum (SR)

Nabavian, O.; M.D.

Figure 9.526

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CARDIOMYOCYTE

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gap

junctions>>electrical
coupling
 “spot” desmosomes>>
mechanical linkage >>
cytoskeleton
 “sheet” desmosomes (or
fasciae adherens)>>
contractile apparatus
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 Cardiomyocytes

can be functionally

separated into:
 (1) the excitation system,
 (2) the ECC system,
 (3) the contractile system.

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Excitation System
Fast-response

action potentials>>
His-Purkinje system
atrial/ventricular
cardiomyocytes
 Slow-response action potentials,
pacemaker cells in the
SA and AV nodes
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phase

0:
much less steep,
phase 1: absent,
phase 2 :
indistinct from
phase 3 in the
slow-response
action potential

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ECC
Ca channel
phosphorylation
Faster contraction

Phospholamban
Faster relaxation
Pictorial E-C Coupling
Na+
Ca++

Sarcolemma

Na+ +
Na

Na+/Ca++ Exchanger

Ca++
Ca++

L-Type Ca++
Channel

Ca++

Ca++ Ca++
Ca++

Plb

SERCA

Ca++

Ca++
Ca++
Ca++
Ca++
++
Ca Ca++
Ca++
Ca++ Ca++ Ca++
++
Ca Ca++
++
Ca++
++
SR Ca++Ca
Ca Ca++ Ca++
RyR
Ca++
Ca++
Ca++
Ca++ Ca++
Ca
++
++

Ca +
+
Ca + C
++
+ a+
C+a ++
Ca ++
+
+
Ca Ca

Ca ++

Nabavian, O.; M.D.

Ca ++
Ca ++ C
Ca ++
a+

+

Ca
Ca++

Ca++
Ca++

Ca +
Ca ++

Ca++
Ca++
+

a+ ++
+ C
Ca
++
Ca
++
Ca
++
Ca 36

10/25/2012
Contractile System
 The

basic working unit of contraction is
the sarcomere.
 A sarcomere is defined as the distance
between Z lines

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Sarcomere

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Structure of Actin and Myosin

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Nabavian, O.; M.D.

Figure 9.4 (a)42
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(b)
Actin

Nabavian, O.; M.D.

Figure 9.4 (c)43

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Troponin

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(+)

(−)

actin

myosin
(−)

actin

(+)

processive movement of
myosin V along F-actin
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actin
actin

troponin
tropomyosin

actin

troponin
tropomyosin

actin

troponin
myosin binding site
tropomyosin

actin

troponin
Ca2+

Ca

2+

Ca2+

Ca2+
Ca2+

Ca

2+

Ca2+

Ca2+

Calcium ions are released from the sarcolemma after stimulation from the T
system
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Ca

2+

Nabavian, O.; M.D.

Ca2+

Ca2+
Ca2+

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Ca

2+

Ca2+

Ca2+
Ca2+

the calcium ions bind to the troponin and changes its shape
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Ca

2+

Ca2+

Ca2+
Ca2+

the calcium ions bind to the troponin and changes its shape
Nabavian, O.; M.D.

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Ca

2+

Nabavian, O.; M.D.

Ca2+

Ca2+
Ca2+

58
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Ca

2+

Nabavian, O.; M.D.

Ca2+

Ca2+
Ca2+

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Ca

2+

Ca2+

Ca2+
Ca2+

the troponin displaces the tropomyosin and exposes the myosin binding sites

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Ca

2+

Nabavian, O.; M.D.

Ca2+

Ca2+
Ca2+

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Ca

2+

Nabavian, O.; M.D.

Ca2+

Ca2+
Ca2+

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Ca

2+

Ca2+

Ca2+
Ca2+

the bulbous heads of the myosin attach to the binding sites on the actin
filaments

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Ca

Ca2+

2+

Nabavian, O.; M.D.

Ca2+
Ca2+

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Ca2+

Nabavian, O.; M.D.

Ca2+
Ca2+

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Ca2+

Ca2+
Ca2+

the myosin heads change position to achieve a lower energy state and
slide the actin filaments past the stationary myosin

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Ca2+

P i Pi P i A

Nabavian, O.; M.D.

Ca2+
Ca2+

P i Pi Pi A

P i Pi P i A

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Pi Pi Pi A

Pi Pi Pi Ca2+
A

Nabavian, O.; M.D.

Ca2+

P i Pi P i A

Ca2+

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Pi Pi Pi A

Pi Pi Pi Ca2+
A

Ca2+

P i Pi P i A

Ca2+

ATP binds to the bulbous heads and causes it to become detached
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Pi Pi Pi A
P i Pi P i A

P i Pi P i A

Ca2+

Ca2+
Ca2+

ATP binds to the bulbous heads and causes it to become detached
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Pi
Pi Pi A
Pi

Pi
Pi Pi A

Pi Pi A

Ca2+

Ca2+
Ca2+

hydrolysis of ATP provides the energy to “re-cock” the heads
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Pi
Pi Pi A
Pi

Pi
Pi Pi A

Pi Pi A

Ca2+

Ca2+
Ca2+

hydrolysis of ATP provides the energy to “re-cock” the heads
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Pi
Pi Pi A
Pi

Pi
Pi Pi A

Pi Pi A

Ca2+

Nabavian, O.; M.D.

Ca2+

Ca2+

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Pi
Pi Pi A
Pi

Pi
Pi Pi A

Pi Pi A

Ca2+

Ca2+

Ca2+

calcium ions are re-absorbed back into the T system
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Pi
Pi Pi A
Pi

Pi
Pi Pi A

Pi Pi A

calcium ions are re-absorbed back into the T system
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Pi
Pi Pi A
Pi

Pi
Pi Pi A

Pi Pi A

the troponin reverts to its normal shape and the tropomyosin move back to block
the myosin binding sites
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Pi
Pi Pi A
Pi

Pi
Pi Pi A

Pi Pi A

the troponin reverts to its normal shape and the tropomyosin move back to block
the myosin binding sites
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Pi
Pi Pi A
Pi

Pi
Pi Pi A

Pi Pi A

the troponin reverts to its normal shape and the tropomyosin move back to block
the myosin binding sites
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Pi
Pi Pi A
Pi

Pi
Pi Pi A

Pi Pi A

phosphocreatine regenerates ATP
Nabavian, O.; M.D.

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Pi
Pi
Pi Pi A

Pi Pi A
Pi Pi Pi A

phosphocreatine regenerates ATP
Nabavian, O.; M.D.

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Pi Pi Pi A

P i Pi Pi A

P i Pi Pi A

phosphocreatine regenerates ATP
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Mechanism of muscle
contraction

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Nabavian, O.; M.D.
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All Things Science - Heart excitation contraction coupling.flv - YouTube.FLV

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NEURAL REGULATION OF
HEART

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 At

rest the heart has a tonic level of PNS
 Atria have more PNS innervation than
ventricles
 M1-M5, M2 most one
 M1,3,5, G proteine
 M2,4 pertussis toxin

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 SNS

more prominent in ventricles
 α receptors >> G protein>> phospholipase
C,D,A
 β receptors >> G protein>> cAMP
 β1,2,3
 β1, both atria ventricle, 80% β2 atria 20%
ventricles
 β2>> β1
 α1,2>>α1A,B,D
 α1 : cardiac hypertrophy

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Adrenoreceptors

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Hormones affecting cardiac
function
Hormone

source

Cardiac action

Increase with CHF

Adrenomedullin

Cardiomyocyte

+ inotropy/
+chronotropy

+

Aldosterone

Cardiomyocyte

?

+

Angiotensin II

Cardiomyocyte

+ inotropy/
+chronotropy

+

Endothelin

Cardiomyocyte

?

+

Natriuritic peptide
ANP

Atria

BNP

Ventricles

Neuropeptide Y
Vasopressin
Nabavian, O.; M.D.

+
+

- Inotropy
Post pituitary

+ inotropy/
+chronotropy

+

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10/25/2012

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Chemoreceptor Reflex
 Mediated

by

– Chemosensitive cells in the carotid bodies and
the aortic body.
– Sinus nerve of Hering and vagus nerves
 At

PaO2 <50 mm Hg or in acidosis

– respiratory centers stimulated and increasing
ventilatory drive.
 Activation

of the parasympathetic system

– reduction in heart rate and myocardial
contractility.
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Bainbridge Reflex
 Bainbridge

(atrial) reflex –
a sympathetic reflex initiated by
increased blood in the atria

 Causes

Nabavian, O.; M.D.

stimulation of the SA node

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Bezold-Jarisch reflex






Elicited by
– chemoreceptors and mechanoreceptors within the
LV wall
– ↑ parasympathetic tone
Noxious ventricular stimuli induces the triad of
hypotension, bradycardia, and coronary artery
dilatation.
Less pronounced in patients with
– Cardiac hypertrophy
– Atrial fibrillation

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Valsalva Maneuver
 Valsalva

maneuver → ↓CO and BP.
 Sensed by baroreceptors → sympathetic
stimulation
 ↑heart rate and myocardial contractility.
 When

the glottis opens, venous return ↑
→↑BP.
 Sensed by baroreceptors → stimulate
parasympathetic efferent pathways to the
heart.
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Cushing Reflex
Cerebral ischemia at the medullary
vasomotor center
↓
Activation of the sympathetic nervous
system
↓
↑ HR, BP, and myocardial contractility
↓
Improve cerebral perfusion
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Oculocardiac Reflex
Stretch receptors
↓
Short and long ciliary nerves
↓
Ophthalmic division of the trigeminal nerve
↓
Gasserian ganglion
↓
Increased parasympathetic tone
↓
Bradycardia.

 Incidence

during ophthalmic surgery30% to 90%.

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Cardiac physiology

Editor's Notes

  1. The L-Type (“long lasting”) Ca Channel is a voltage controlled gate located in the T-tubules of the sarcolemma. Ca enters the cell through this channel during phase 2 of the action potential. This Ca stimulates further Ca release from the SR via the RyR. This process is referred to as calcium induced calcium release (CICR). Once contraction is complete, Ca is dissociates from TN-C and is reabsorbed by the SR via the SERCA pump. Phosphorlyation of phospholamban (Plb) increases the activity of SERCA. Phosphorylation occurs when a phosphate group binds to a molecule. Ca is also removed through the Na/Ca exchanger in a ratio of 3 Na ions for each Ca ion. An ATP dependent Ca pump also helps remove Ca from the cell.