Electrophysiology of myocardium.

Myocardial Mechanics. Assessment

of cardiac function

Dariusz Nowak

Heart

• Right heart – pumps blood through lungs
• Left heart – through peripheral organs
Atrium –weak primer pump, Ventricle – main pump
1 atrial muscle
2 ventricular muscle
3 excitatory and conductive muscle fibers – responsible for rhythmical

beating of the herat

Cardiac musccle
• Striated (like sceletal muscle)
• Myofibrils (like sceletal muscle)
• Intercalated discs – very low electrical resistance, fast diffusion of

ions

• Syncytium (of many heart muscle cells)

Heart

• Atrial syncytium – two atria
• Ventricular syncytium - two ventricles
Separated by fibrous tissue (electrical isolation)

– no conduction of potentials

Conduction only through A-V bundle –

specialized conductive system

Atria contract a short time ahead of ventricles

Heart

Sinoatrial node (SA) – pacemaker
↓ Electrical impulses
Spread rapidly to right and left atrium (contraction)
↓
Atrioventricular junction (AV) – delayed conductance
↓ allows atrial conduction to boost the filling

of the ventricles

prior to the onset of their contraction
Conducting fibers
↓ Bundle of His, right and left bundle branch,

Purkinje fibers

Left and right ventricles contraction (left slightly before

the right)

Cardiac muscle -Ions concentration

Outside of the cell inside the cell
Ca

2+

2 mM (→) 10

-7

M

Na

+

145 mM (→) 15 mM

K

+

4 mM (←) 160 mM

Cl

-

120 mM (→) 5 mM

Resting muscle cell of the ventricle

transmembrane potential

-90 mV (inside negative to the outside)

Resting transmembrane potential

Equilibrium potential for K

+

Veq = - 61.5 x Z

-1

x log ([C]

i

x [C]

o-1

)

Z – ion charge
C

i

– ion intracellular concentration

C

o

– ion extracellular concentration

Veq = - 61.5 x log ([K

+

]

i

x [K

+

]

o-1

)

Ideal membrane

Resting membrane potential of

pacemaker cells

SA (sino-atrial) node
AV junction
His-Purkinje network (specialized conduction system)
• Do not exhibit constant resting potentials
• Capable of spontaneous depolarization
• Gradual fall in the negative resting potential toward zero

(progressively less negative)

• Gradual decrease in K

+

permeability

• Less K

+

movement outward while Na

+

movement inward is

the same

• Automaticity
• Spontaneous depolarization

→

threshold potential

→

spontaneous action potential

Self excitation of SA cells

Threshold potential (voltage) = - 40 mV
↓
Activation of calcium and sodium channels
Rapid influx of Na

+

and Ca

2+

ions

↓
Action potential
Cesation of Na

+

and Ca

2+

influx , onset of large K

+

diffusion out of the cell

↓
Reduction of intracellular potential back to negative

resting value (end of action potential)

↓
Hyperpolarization and then gradual decrease in negative

resting potential

Impulse transmission through atria , AV node ,

ventricles

SA node fibers – direct connection with atrial muscle fibers

↓

Internodal pathways (anterior, middle, posterior)

↓

To AV node
AV node and AV-bundle delay transmission of the cardiac

impulse from atria into ventricles. Total delay is 0.16 s

What is a significance of this phenomenon ?
• atria pump their blood into ventricles before the onset of

their contraction

Why ?
Slow conduction (less gap junctions, intercalated discs) and

icreased electrical resistance.

Conductance

• Purkinje fibers – rapid transmission, 0.03 s

(left and right bundle branches)

Normal state
• one-way conduction through A-V bundle
• Conduction is only from atria to ventricles
• Ensures that ventricular muscle fibers begin

to contract at almost the same time

Peacemaker of the heart
S-A node 110/min ? Pulse 70-80/ min
A-V node 40-60/min (intrinsic rhythm)
Purkinje fibers 15-40/min
S-A node is the normal pacemaker of the heart

Pacemaker

Abnormal pacemakers
Ectopic pacemaker – abnormal sequence of contraction

Blockade of impulses transmission from S-A node to other

parts of heart

↓
New pacemaker – with highest intrinsic rhythm e.g. A-V node

or other

part of A-V bundle

Sudden A-V bundle block
• 5-20 s delay in emission of impulses by a new pacemaker
• Lack of blood in the brain
• Stokes-Adams syndrome
• New heart rate is lower

Conductance

Cardiac nerves
Sympathetic – distributed to all parts of the heart also to

ventricular muscle

Parasympathetic (the vagi) – mainly to S-A node, A-V node ,

less to atria, traces to ventricle

Vagal (parasympathetic) stimulation , acetylocholine
• Decreases the heart rate
• Slows (even block) impulses conduction – mainly in A-V

junction

• Ventricular escape phenomenon

How can we do vagal stimulation ?

Conductance

Vagal stimulation
• Induces leakage of K

+

out of the

fibers

• Membrane hyperpolarization
• Longer time is required to reach

the threshold potential

Conductance

Sympathetic stimulation

• Acts via norepinephrine
• Increases the heart rate
• Increases the rate of conduction
• Increases the force of contraction
• Increases membrane permeability for Na

+

(faster depolarization) accelerates self
excitation

Conductance

S-A node – intrinsic rhythm ≈ 110/min
Pulse 70-80/min
Heart after transplantation - pulse ≈ 110 /min
Polyneuropathy in patient with diabetes – pulse

110/min

vagal activity
↓ -
S-A node - resultant frequency 70-80/min
↑ +
Sympathetic activity

Fast-response action potentials

• Cells in the atrial and ventricular muscle
• Parts of the conduction system
• Relatively high (more negative) resting membrane

potential –85 to –95 mV

• Relatively stable resting membrane potential
• Very rapid onset of action potential

Composed of the follwing phases
0 – rapid upstroke (spike)
1- recovery of the initial overshoot to a positive membrane

potential phase

2- plateau period phase
3- repolarization phase
4 – resting membrane potential phase

Fast-response action potentials

Phase 0
• Threshold potential ≈ -70 mV
• Very rapid (voltage dependent) increase in membrane

permeability for Na

+

• Inward Na

+

current

• Can be inhibited by blockers of Na

+

fast channels

• Positive overshoot = +20 mV
Phase 1
• Starts of the repolarization process of the membrane
• Closing of the fast Na

+

channels – it is not possible to

initiate another action potential - refraction

• Inward movement of Cl

-

Fast-response action potentials

Phase 2 – Plateau phase
• Slow inward Ca

2+

current

• Slow inward Na

2+

current

• Movement of K

+

out of the cell

Verapamil (blocker of slow Ca

2+

channels) causes

abbreviation of the plateau phase

Phase 3
• Raid repolarization of the cell membrane
• Inactivation of slow Ca

2+

and Na

+

channels

• Rapid outward movement of K

+

• Lidokaine shortes this phase

Refractoriness

Absolute refractory period – period during which the

membrane cannot be reexcited by an outside
stimulus regardless of the level of voltage applied.

Effective refractory period - only local response, no

propagation of action potential.

Relative refractory period – action potential can be

propagated but larger stimulus should be used
than normal

Supernormal period – short period during which the

cell is more excitable than normal. Weaker
stimulus can initiate a propagated potential.

Full recovery time – time from the onset action

potential to the end of the supernormal potential

Refractoriness

Majority of drugs used to treat

cardiac rhythm disturbances
affects the refractory periods of
heart cells

e.g. Increase the action potential

duration and the effective
refractory period

Cardiac pump

Cardiac cycle – from one heart beat to the next one
• Systole – period of contraction
• Diastole – period of relaxation, heart fills with blood
Increase in heart rate causes shortening of cardiac cycle due

to shortening of diastole

Pathology – „fast arrhythmias” – high shortening of diastole

impairs heart filling with blood and causes the decrease in
cardiac output

Atria contribute to 20-30% (25%) of ventricle filling with blood
Atrial fibrillation – no effective contraction of atria – maximal

cardiac output decreases by 20-30% , decreased tolerance
of exercise

Cardiac pump

Function of valves
Atrioventricular (A-V) valves ; tricuspid and

mitral valves, prevent the blood backflow from
ventricles to the atria during systole

Semilunar valves; aortic and pulmonary –

prevent blood backflow from aorta and
pulmonary arteries into ventricles during
diastole

Cardiac Pump

Pv – pressure in the ventricle , Pat – pressure in the atria,
Par – pressure i aorta , Ppa – pressure in pulmonary artery

Diastole (filling of ventricles)
Pv – decreases
When Pv < Par and Ppa semilunar valves are closed
When Pv < Pat A-V valves are open
• Period of rapid filling of the ventricles (lasts ≈ 1/3 of

diastole)

• Period of slow filling (next 1/3 of diastole)
• Atria cotraction – additional flow into the ventricle (last 1/3

of diastole)

Cardiac pump

Ventricular contraction begins
• Isovolumic (isometric) contraction
Rapid increase in Pv
When Pv > Pat – A-V valves are closed
but Pv < Par and Ppa – semilunar valves are still closed
No ventricle emptying, no blood flow into aorta and

pulmonary artery.

• Period of ejection
When Pv>Par (80 mmHg) and Pv> Ppa (8mmHg) –semilunar

valves are open

• Period of rapid ejection 70% of blood, 1/3 of period
• Period of slow ejection 30% of blood , 2/3 of period

Cardiac pump

End of systole
Relaxation begins suddenly
Rapid decrease in intraventricular pressure (Pv)
Pv> Pat A-V valves are closed
When Pv< Par and Ppa semilunar valves start to be

closed

Period of isovolumic (isometric) relaxation
Further decrease in Pv , (Pv<Pat), A-V valves start to be

open

↓

Period of rapid filling of the ventricles

Cardiac pump

End-diastolic volume ≈ 110-120 ml
End-systolic volume

≈

40-50 ml

Stroke volume output = EdV – EsV = 120ml-50ml =70

ml

Ejection fraction = (stroke volume/ EdV) x 100% > 60%

Stroke volume x heart rate = ?

Cardiac pump

Four major factors that influence ventricular performance;

preload, afterload, inotropic sate, heart rate

Preload
• Tension of the wall at the end of diastole – determines

resting fibers length

• Practically this is ventricular end-diastolic volume or

ventricular end-diastolic pressure

• Affects the performance of the heart through „Starlings

law of the heart

• Increase in the end-diastolic volume of the ventricle

causes increase in stroke volume and velocity of ejection.

Peak pressure in the isovolumetric beat is augmented.

• Significance of atria contraction for ventricle function

Cardiac pump

Afterload
Major determinant of afterload – systolic aortic

pressure or systolic left ventricle pressure.

Lowering the aortic pressure (while aortic valve

is shut) → left stroke volume is higher and
blood is ejected with higher velocity

Rise in the aortic pressure causes the decrease

in stroke volume

Cardiac pump

Inotropic state
Experimental conditions : preload and afterload are

constant

Positive intotropic agent - digitalis
Negative inotropic agent - beta-blocker
They cause changes inventricle contractility
Rise in contracility increases:
• Peak pressure isovolumetric systole
• Stroke volume
• Velocity of ejection

Cardiac pump

Heart rate
Frequency of cardiac contraction influences myocardial

inotropic state – force-frequency (staircase) relation.

Increase in heart rate increases myocardial contractility
This effect for one beat is small
For cardiac output (CO – cardiac performance per minute) is

significant

Heart rate 70/min , stroke voume 67 ml
CO=70 x 67 = 4690 ml/min
Heart rate 140/min, stroke volume 74 ml (increase by 7 ml)
CO=140 x 74 = 10360 ml/min
CO at stroke volume 67 ml = 140 x 67 = 9380 ml/min
Effect of staircase = 10360-9380 = 980 ml/min ≈ 1l/min