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Lecture 4

Physiological properties of
myocardium. Cardiac cycle
 LECTURE OUTLINE
1. General characteristic of functional system of circulation
2. Functional anatomy of cardiac muscle
3. Physiological properties of cardiac muscle
4. General characteristic of cardiac cycle
5. Analysis of cardiac cycle events
1) Atrial systole & diastole
2) Ventricular systole
3) Ventricular diastole
6. Dynamics of heart volumes
 Blood circulation system
is physiological system which accomplishes blood movement through the
vessels and supplies metabolic needs of all organs and tissues

Vascular
system Mechanisms
Heart vessels of lesser Blood of neural and
and greater humoral
circulation regulation

Pumps blood Direct blood Correspondence

providing flow and between
blood flow and provides circulating blood
pressure in pressure in volume and
the vascular vascular volume of
system system vascular bed

Lumen of
Volume of
CO = HR × SV vascular bed -
circulating blood 3
R
 FUNCTIONS OF CARDIOVASCULAR SYSTEM

Function explanation
1 To deliver blood  to the tissues, providing essential nutrients
to the cells for metabolism
 removing waste products from the cells.

2 Heart serves as the generates the pressure to drive blood through a

pump series of blood vessels
3 The vessels that carry under high pressure and contain a relatively
blood from the heart small percentage of the blood volume.
to the tissues are the
arteries
 FUNCTIONS OF CARDIOVASCULAR SYSTEM
Function explanation
4 The veins, which carry under low pressure and contain the largest
blood from the tissues percentage of the blood volume.
back to the heart
5 Thin-walled blood Exchange of nutrients, wastes, and fluid occurs
vessels, called across the capillary walls.
capillaries
6 Homeostatic functions regulation of arterial blood pressure;
it delivers regulatory hormones from the endocrine
glands to their sites of action in target tissues;
it participates in the regulation of body
temperature;
it is involved in the homeostatic adjustments to
altered physiologic states such as hemorrhage,
exercise, and changes in posture.
 Left and Right Sides of the Heart
Each side of the heart has two chambers, an atrium and a ventricle, connected by
one-way valves, called atrioventricular (AV) valves permitting blood to flow only in
one direction, from the atrium to the ventricle.
The left heart functions The right heart functions
The left heart and the systemic arteries, The right heart and the pulmonary arteries,
capillaries, and veins are collectively called capillaries, and veins are collectively called
the systemic circulation. the pulmonary circulation.
The left ventricle pumps blood to all organs The right ventricle pumps blood to the
of the body except the lungs. lungs.
The blood is pumped sequentially from the left heart to the systemic circulation,
to the right heart, to the pulmonary circulation, and then back to the left heart.
The rate at which blood is pumped from ventricle is called the cardiac output (CO).
The CO of the left ventricle equals the CO of the right ventricle in the steady state.
The rate at which blood is returned to the atria from the veins is called the venous
return (VR). VR to the left heart equals VR to the right heart in the steady state.

Finally, in the steady state, CO from the heart equals VR to the heart
Pulmonary and systemic circuits

7
 The steps in one complete circuit through the
cardiovascular system
1. Oxygenated blood flows from lungs via 4 pulmonary vein to the left atrium then
to the left ventricle through the mitral valve (the AV valve of the left heart).
2. Blood leaves the left ventricle through the semilunar aortic valve. Blood is ejected
forcefully into the aorta (cardiac output.)
3. Cardiac output is distributed among various organs. The total cardiac output
of the left heart is distributed among the organ systems via sets of parallel arteries.
• 15% - to the brain,
• 5% is delivered to the heart,
• 25% is delivered to the kidneys,
• GIT – 25%
• Skeletal muscles – 25%
• Skin – 5%
• Given this parallel arrangement of the organ systems, it follows that the
total systemic blood flow must equal the cardiac output.
 The steps in one complete circuit through
the cardiovascular system

4. The blood leaving the organs is venous blood and contains waste products from
metabolism, such as carbon dioxide (CO2). Venous blood is collected in vena cava
which carries blood to the right heart - Venous return to the right atrium equals
cardiac output from the left ventricle.
Venous blood flows from the right atrium to the right ventricle through the AV valve
in the right heart, the tricuspid valve.
5. Blood is ejected from the right ventricle into the pulmonary artery - blood is
ejected through the semilunar pulmonic valve into the pulmonary artery, which
carries blood to the lungs.
CO of RV = CO of LV
In the capillary beds of the lungs, gas exchange happens thus, the blood leaving
the lungs has more O2 and less CO2 than the blood that entered the lungs
6. Blood flow from the lungs is returned to the left atrium via the pulmonary
vein to begin a new cycle.
 Valvular apparatus

• The atrioventricular valves

regulate the openings between
the atria and ventricles
• Right AV – tricuspid
• Left AV – bicuspid (mitral)
• The semilunar valves regulate
the openings between the
ventricles and the great arteries:
• Pulmonary trunk – pulmonary
valve
• Aorta – aortic valve
Functions of valves:
1. Provide one-way direction of blood flow
2. Prevent backflow of blood
3. Create pressure gradient
10
 CARDIAC ELECTROPHYSIOLOGY

includes following processes involved in the electrical

activation of the heart:
• the cardiac action potentials;
• the conduction of action potentials along specialized
conducting tissues;
• excitability and the refractory periods;
• the modulating effects of the autonomic nervous system
on heart rate, conduction velocity, and excitability;
• the electrocardiogram (ECG).
 PROPERTIES OF CARDIAC TISSUE
Cells within the heart are specialized for different functional roles.
In general, these specializations are for automaticity, conduction, contraction
and endocrine function.

№ Property Type of cells Function

1 Automaticity Sinoatrial (SA) specialized for automaticity → spontaneously
node cells depolarize to threshold and have the highest
. intrinsic rhythm (rate), making them the
pacemaker in the normal heart.
Their intrinsic rate is ~100/min.

Atrioventricular have the second highest intrinsic rhythm (40-

(AV) node cells 60/min). Often, these cells become the
pacemaker if SA node cells are damaged

Although not But Do exhibit spontaneous depolarizations with

“specialized” for a rate of ~20/min
automaticity -
Purkinje cells
 PROPERTIES OF CARDIAC TISSUE

2 Conduction AV node: Specialized for slow conduction.

All cardiac tissue They have small diameter fibers, a low
conducts electrical density of gap junctions, and the rate of
impulses, but the depolarization (phase 0) is slow in
following are comparison to tissue that conducts fast.
particularly Purkinje Specialized for rapid conduction.
specialized for this cells: Their diameter is large, they express
function. many gap junctions, and the rate of
Conducting cells: the depolarization (phase 0) is rapid.
atrial internodal tracts, These cells constitute the HIS-Purkinje
the system of the ventricles.
AV node, the bundle of
His, and the Purkinje
system.
 PROPERTIES OF CARDIAC TISSUE

3 Contraction Contractile Constitute the majority of atrial and

cells ventricular tissues and are the working cells
of the heart.
Action potentials in contractile cells lead to
contraction and generation of force or
pressure.
4 Endocrine atrial natriuretic factor (ANF), brain
natriuretic peptide (BNP)
now designated cardiac natriuretic peptides
(cNPs)
 PHYSIOLOGICAL PROPERTIES OF CARDIAC MUSCLE

Automaticity Excitability Conductivity Contractility

Ability to Ability to Ability to

Ability to
generate AP in conduct AP change cell’s
generate AP
response to without length and/or
spontaneously
stimulation diminish tension

Declining
Law
gradient of Atrioventricular Law of
“all-or-none”
automaticity of delay Frank-Starling
of Bowditch
Gaskell

Supply pumping function of the heart 15

CONDUCTING SYSTEM OF THE HEART
 CONDUCTING SYSTEM OF THE HEART
Description Firing Velo-
Rate city
SA node is located at the junction of the superior vena cava with 60-100 -
SA node the right atrium imp/min

Atrial 3 bundles that connect the SA node to the AV node: - 1 m/sec

internodal the anterior (Bachmann bundle), middle (tract of Wenckebach),
tracts and posterior (tract of Thorel) tracts.

is located in the right posterior portion of the interatrial septum 40-60 0.01–
AV node slow velocity ensures that the ventricles have sufficient time to fill imp/min 0.05
with blood before they contract. m/sec

From the AV node, the AP enters the specialized conducting system His bundle – 2–4
Bundle of which is bundle of His. 30-40 m/sec
His, It then invades the left and right bundle branches and then the Purkinje
Purkinje smaller bundles of the Purkinje system. fibers
system Conduction through the His-Purkinje system is extremely fast, and – 15–20
it rapidly distributes the action potential to the ventricles. imp/min
The action potential also spreads from one ventricular muscle cell 1 m/sec
Ventricles to the next, via low resistance pathways between the cells.
 Action Potentials of Ventricles, Atria, and the
Purkinje System

The AP in these tissues shares the following characteristics:

1. Long duration:
150 msec in atria,
250 msec in ventricles,
300 msec in Purkinje fibers
(skeletal muscle - 1 to 2 msec).
The longer the AP, the longer the cell is refractory to firing another AP.
Thus, atrial, ventricular, and Purkinje cells have long refractory periods
compared with other excitable tissues.
2. Stable resting membrane potential – these cells exhibit a stable, or constant,
RMP.
3. Plateau - is a sustained period of depolarization, which accounts for the long
duration of the AP and, consequently, the long refractory periods.
Action potential in a ventricular muscle fiber
and an atrial muscle fiber
 The phases of the action potential
Phase Membrane conductance Type of Relation
channels to ECG
Phase 0, high Na+ conductance voltage-gated, QRS
upstroke - fast Na+ complex
rapid channels
depolarization
Phase 1, initial inactivation gates on the Na+ channels -----
repolarization close, → inward Na+ current ceases
the K+ conductance is high → K+ flows voltage-gated -----
out of the cell K+ channels

Phase 2, ↑ in Ca2+ conductance → slow inward Ca2+ L-type ST

plateau Ca2+ current, also initiates the release channels segment
relatively of more Ca2+ from intracellular stores for (slow)
stable, excitation-contraction coupling - Ca2+-
depolarized induced Ca2+release
membrane an outward K+ current voltage-gated
potential inward Ca2+ current is balanced by the K+ channels
outward K+ current (delayed
rectifier)
 The phases of the action potential
Phase Membrane conductance Type of Relation
channels to ECG
Phase 3, ↓ in Ca2+ and an ↑ in K+ (higher than • L-type channels T wave
repolarization at rest) begin closing,
an increase in the outward K+ but rectifying K+
current (IK) currents still exist

Phase 4, membrane potential is stable again, Fast Na+, L-type

resting and inward and outward currents are Ca2+, and
membrane equal. rectifying K+
potential, or The high conductance to K+ channels close,
electrical produces an outward K+ current but K+
diastole channels remain
open.
Action Potential of SA node
 Action Potential of SA node

The following features of the AP of the SA node are different

from those in atria, ventricles, and Purkinje fibers:
 The SA node exhibits automaticity - it can spontaneously
generate action potentials without neural input;
 It has an unstable resting membrane potential, in direct
contrast to cells in atrial, ventricular, and Purkinje fibers;
 It has no sustained plateau.
Phases of an Action Potential of SA
node

Find the difference between:

A and B
A and C
 Phases of an Action Potential of SA node
Phase Events
Phase 0, is the result of an increase in gCa and an inward Ca2+ current
upstroke carried primarily by L-type Ca2+ channels.
(also T-type Ca2+ channels in SA node, which carry part of the
inward Ca2+ current of the upstroke)
Phases 1 and 2 are absent
Phase 3, due to an increase in gK, there is an outward K+ current
repolarization
Phase 4, maximum diastolic potential (most negative) is about −65 (-60)
spontaneous mV, produced by the opening of Na+ channels and an inward
depolarization or Na+ current, which is turned on by repolarization from the
pacemaker preceding action potential, thus when slow depolarization bring
potential the membrane potential to threshold, the T-type Ca2+ channels
are opened for the upstroke.
If the rate of phase 4 depolarization increases (threshold is reached more
quickly), the SA node will fire more AP per time, and heart rate will increase.
Conversely, if the rate of phase 4 depolarization decreases, threshold is reached
more slowly, the SA node will fire fewer AP per time, and heart rate will decrease.
 Excitability and Refractory Periods
Excitability is the capacity of
myocardial cells to generate
action potentials in response
to inward, depolarizing current

Excitability is the amount of

inward current required to
bring a myocardial cell to the
threshold potential

The excitability of a myocardial cell varies over the course of the action
potential, and these changes in excitability are reflected in the refractory
periods
 Excitability and Refractory Periods
Period Events
Absolute most of the duration of the AP, most of the Na+ channels are closed.
refractory Includes: upstroke, the entire plateau, and a portion of the
period repolarization. Ends when the cell has repolarized to about −50 mV

Effective The ERP is slightly longer than, the ARP. At the end of the ERP, the Na+
refractory channels start to recover.
period The distinction between the ARP and ERP is that absolute means
absolutely no stimulus is large enough to generate another AP; effective
means that a conducted AP cannot be generated
Relative The RRP begins at the end of the ARP and continues until the cell mem-
refractory brane has almost fully repolarized. More Na+ channels have recovered
period and it is possible to generate a second action potential, although a
greater-than-normal stimulus is required.
Supra- follows the RRP and begins when the membrane potential is −70 mV
normal and continues until the membrane is fully repolarized back to −85 mV.
period less inward current is required to depolarize the cell to the threshold
potential (the Na+ channels are recovered)
 CARDIAC CYCLE

The cardiac events that occur from the beginning of one

heartbeat to the beginning of the next one
VC = VS+VD or AC = AS+AD
CC lasts 0.8 sec if HR is 75 bpm
CC= 60 sec/75 bpm=0.8
VC = 0.8 = VS 0.33 + VD 0.47
AC = 0.8 = AS 0.1 + AD 0.7
 To characterize events happening
in each period of cardiac cycle we
need to know:

• 1. Direction of blood flow throughout the

heart chambers
• 2. State of Valves (closed or opened)
• 3. Value of pressure in each chamber
 Analysis of cardiac cycle events

SYSTOLE sec DIASTOLE sec

Atrial systole 0.1 Atrial diastole 0.7
Ventricular systole 0.33 Ventricular diastole 0.47

I. Period of tension 0.08 I. Protodiastolic period 0.04

1) phase of asynchronous 0.05 II. Period of isometric 0.08
contraction relaxation
2) phase of isometric 0.03 III. Period of filling 0.25
contraction
II. Period of ejection 0.25 1) phase of maximal filling 0.08
1) phase of maximal ejection 0.12 2) phase of reduced filling 0.17
2) phase of reduced ejection 0.13 IV. Presystolic period 0.1

30
 Total pause or total diastole of the heart
precedes atrial systole – 0,37 sec

1. Atria and ventricles are relaxed

2. Sphincters of veins are relaxed
3. Blood flows from veins to atria
4. AV valves are opened
5. From atria to ventricles
6. SL valves are closed
7. Pressure about 0
8. Ventricles get about 80 % of EDV before atria
contract
Atrial systole - 0.1 sec
• Both atria contract
• Pressure: RA - 5-8 mm Hg;
• LA - 10-12 mm Hg
• Sphincters of veins are closed
• Blood is not entering atria
• AV valves are opened
• SL valves are closed
• Blood flows from atria to ventricles
(active filling of ventricles – 20 % of EDV) – “atrial kick”
• S4 – is not audible in normal adults
• Ventricles get complete EDV ( about 135 ml)
• Amount of blood in the ventricle at the end of diastole
is known as end diastolic volume (EDV)
 Atrial diastole
• 1. Duration – 0.7 sec
• 2. Relaxation of atrial myocardium
• 3. Relaxation of sphincters of veins
• 4. Blood flows from veins to atrial
• 5. AV valves will become closed
 Ventricular systole = 0.33 s
I. Period of tension = 0.08 s
1) Phase of asynchronous contraction = 0.05 s
• Depolarization and following contraction of ventricles starts from the apex
toward the basis of the heart
2) Phase of isovolumetric contraction (IVC) = 0.03 s
• Pressure:
• RV - 10-15 mm Hg → RV - 25 mmHg > 8 mmHg (PA)
• LV – 70-80 mm Hg → LV - 120 mmHg > 80 mmHg (Aorta)
• ∆ P forces AV valves to close thus preventing backflow of blood
into atria (Ventricular P > Atrial P) producing S1 (systolic) –
lub - low-pitched, muffled (unvoiced) and prolonged
• AV valves just got closed
• SL valves still closed
• 1st phase of all valves closed
 Ventricular systole - Period of ejection = 0.25 s

1) phase of maximal ejection = 0.12 s

2) phase of reduced ejection = 0.13 s
• ∆ P forces the semilunar valves to open → ejection begins
• Blood is ejected from LV to aorta and from RV to pulmonary artery through
opened SL valves
• Ejection is provided by pressure gradient between ventricles and arteries –
peak of ventricular pressure – rapid ejection
• In LV – 120 mm Hg but in aorta – 80 mm Hg
• In RV – 25 mm Hg but in pulmonary artery – 8 mm Hg
• Amount of blood ejected from ventricle to artery in 1 heart beat is called stroke
volume (SV) - 60-80 ml
• Amount of blood remaining in the ventricle after ejection is called end systolic
volume (ESV) – 50-65 ml
• ESV=EDV-SV; SV=EDV-ESV; EDV=ESV+SV
• At the end of this phase the strength of contraction reduces →pressure
starts to decrease → reduced ejection
 Ventricular diastole = 0.47 s

• Isovolumetric relaxation begins with protodiastolic

period
• the ventricles relax and ejection comes to an end
• LVP and RVP is below aortic (120 mm Hg) and pulmonary artery (25 mm
Hg)
• This ∆ P forces SL valves to close
• Producing the S2 (diastolic), a louder dub
• (protodiastolic) - high-pitched, voiced and short
• SL valves just got closed
• AV valves still closed
• 2nd phase of all valves closed
 Ventricular diastole

Period of ventricular filling = 0.25 s

1)Phase of maximal filling = 0.08 s
2)Phase of reduced filling = 0.17 s
•Pressure in the ventricles rapidly decreases
below atrial pressure → opening of AV valves
→blood that accumulated in atria (since AV valves
closed) flows rapidly into ventricles (passive VF)
•Heart sound S3 (rapid VF) – normal in
children but not in adults
The most ventricular filling is completed during
early diastole (great importance)
37
•That’s why in case of tachycardia (duration of
diastole and VF decreases) the filling is not
seriously impaired
•But with HR 200 bpm and more the
inadequate filling (insufficient) will occur
Events of the Cardiac Cycle
 Ventricular Volumes
• End-diastolic volume (EDV): volume of blood in the ventricle at the end of
diastole
• End-systolic volume (ESV): volume of blood in the ventricle at the end of
systole
• Stroke volume (SV): volume of blood ejected by the ventricle per beat
• SV = EDV − ESV
• Cardiac output (CO): the total volume of blood ejected per unit time is the.
• Thus, CO depends on SV and HR.
• Cardiac output is approximately 5000 mL/min in a 70-kg man (based on a
stroke volume of 70 mL and a heart rate of 72 beats/min).
• CO = SV× HR
• Ejection Fraction (EF): is the fraction of the end-diastolic volume that is
ejected in one stroke volume (describing the effectiveness of the ventricles
in ejecting blood)
• EF = SV/EDV
• (should be >55% in a normal heart)
Pressure differential

41
 Pressure-volume loops and cardiac cycle

Phases—left ventricle:
1. IVC - period between mitral valve closing and aortic valve opening;
2. Systolic ejection - period between aortic valve opening and closing
3. IVR - period between aortic valve closing and mitral valve opening
4. Rapid filling- period just after mitral valve opening
5. Reduced filling- period just before mitral valve closing