Unit Four
Circulation
The cardiovascular system
consists of the heart and blood vessels
Vena cava
Right Atrium
Right Ventricle
Pulmonary Artery
Pulmonary
capillary
Systemic
capillary
Left ventricle
Left atrium
Aorta
Pulmonary
vein
Tissue fluid circulation
Blood circulation
(Power)
Lymph circulation
Cerebral fluid circulation
人体淋巴系统
人体脑室系统
人体脑脊液循环
The valves ensure one-way flow of the
blood in the cardiovascular system
AV valves
Bicuspid valve (Mitral valve)
Tricuspid valve
Arterial valves
Venous valves
Lymphatic valves
Aorta semilunar valve
Pulmonary semilunar valve
The function of circulatory system
 Transports materials throughout the body
Nutrients, water, gases (O2, CO2), hormones, etc
 Keeps homeostasis of internal environment
 Regulates body temperature
 Endocrines
atrial diuretic peptide, vascular active substances
Excitation & conduction
（Electrical activity）
Cardiac Physiology
Pumping function
(mechanic activity）
Chapter 9
Cardiac
Electrophysiology
The importance of cardiac EP
1. Basis of cardiac contraction and pumping activity
2. Target of drugs
3. Arrhythmia: diagnosis, treatment
4. Research
Section 1
The electrical activity of
the cardiomyocyte
Transmembrane potential
of the cardiomyocyte
 Resting potential:
varies with different cells
 Maximal diastolic potential:
shown only in cells with
autorhythmicity
Types of the cardiomyocytes
 Fast response cells:
1. Contractile (working) cells:
ventricular myocytes
atrial myocytes
2. Autorhythmic cells: His bundle, Purkinje fibers
Internodal pathways
 Slow response cells:
1. Autorhythmic cells: pacemaker cells in sinus node,
atrial-nodal zone and nodal-His zone of the AV node
2. Non-autorhythmic cells: cells in AV nodal zone
The structure of AV node
internodal pathways
atrial-nodal zone
AV node
nodal zone
nodal-His zone
His bundle
窦房结
心房肌
房室结
希氏束
浦氏纤维
心室肌
1. Transmembrane potential of the
cardiac working (contractile) cells
 Resting potential:
80  90 mV, IK1 channel (Kir channel)
 Action potential:
fast response, 4 phases
AP of atrial myocyte
AP of ventricular
myocyte
Ionic basis of the AP of cardiac contractile cells
 Phase 0 (depolarizing phase): INa
 Phase 1 (fast repolarizing phase 1): Ito
 Phase 2 (plateau phase): IK, ICal
 Phase 3 (fast repolarizing phase 2) : IK, IK1
 Phase 4 (resting potential): IK1, Na+ pump, etc
I Kr
I Ks
Figure 9-6 ICal in
ventricular cell
Figure 9-7 IKr and IKs in
dog ventricular cell
2. Diastolic depolarization in cardiac
autorhythmic cells
 Purkinje fiber:
If, IK
 P cell in the sinus node:
If, ICaT, IKr
Ionic basis of the AP of Purkinje fibers
 Phases 0-3 : similar with contractile cell
 Phase 4 (diastolic depolarization): If, IK
Different names of If:
Ih (hyperpolarization activated
cation channel)
Pacemaker current
Ionic basis of If:
Na+ K+
Ionic basis of the pacemaker cell in sinus node
 Phases 0: ICal
 Phase 3: IK
 Phase 4: If, ICaT
A rightward shift of the curve
means a greater If at the same
membrane potential
Early afterdepolarization
Delayed afterdepolarization
Section 2
The electrical characteristics
of the cardiomyocyte
Physiological characteristics of cardiomyocyte
 Excitability （兴奋性）
 Conductivity （传导性）
 Autothythmicity (or pacemaker activity)
（自律性）
 Contractility （收缩性）
1. Excitability
Factors that determine the excitability:
(1) Na+ (or Ca2+) channel properties:
resting
activation
excitable
excitated
inactivation
non-excitable
ARP, ERP
(2) The distance between resting potential (maximal
diastolic potential) and threshold potential
Periodic changes of the excitability
of LV cardiomyocyte after excitation
absolute refractory period (ARP) (0-55mV)
effective refractory period (ERP) (0-60mV)
relative refractory period (RRP) (60-80mV)
supranormal period (SNP) (80-90mV)
Normal excitability (90mV)
Postrepolarization refractoriness
1. Normal: slow response cell, the recovery of ICal is
slow, such that the membrane is still refractory
after full repolarization.
2. Abnormal: myocardial infarction/reperfusion
PVC
Compensatory pause
♣ Factors that affect the excitability
 Ions:
 [K+]o:
slight high [K+]o increases excitabilty
serious high [K+]o decreases excitabilty
low [K+]o increases excitabilty
 [Ca2+]o:
high [Ca2+]o slightly decreases excitabilty
via affecting Na+ channel
low [Ca2+]o increases excitabilty
 pH:
low extracellular pH (acidosis)
2. Autorhythmicity (自动节律性）
 Sinus node is the dominant pacemaker of the heart
 Sinus rhythm（窦性节律）
 Latent pacemaker (潜在起搏点）
 Ectopic pacemaker （异位起搏点）
 Ways by which sinus node controls the heart:
 Capture (抢先占领）
 Overdrive suppression (超速驱动抑制）
 Factors that affect the autorhythmicity:
 Velocity of diastolic depolarization
 Maximal diastolic potential
 Threshold potential
 Autonomic nerve control of the autorhythmicity:
 Sympathetic discharge increases the autorhythmicity
 Vagal nerve discharge decreases the autorhythmicity
Key point
Question: Why cardiocyte has a very long APD?
Answer: To guarantee that the heart does not
tetanize (强直收缩，痉挛）, but excites and
contracts periodically.
3. Conductivity (传导性）
The myocardium is a functional syncytium (机能合胞体）,
the excitation can conduct directly between cardiac cells.
 Conduction pathways
1. The conduction of excitation in the atrium
 Preferential pathway (inter-atrial pathway)
 Inter-atrial contractile cell conduction
A-V block
1st degree: A-V conduction slowing
P-R interval prolongation
1:1 conduction
2nd degree: (1) PR interval gradual
prolongation, then a QRS lost
(2) 2:1 conduction, PR interval
may not necessarily prolong
3rd degree: complete AV block,
AV dissociation
2. The conduction of excitation in the ventricle
How to measure cardiac conduction?
1. Electrical mapping (标测技术）
Multi-electrode array
2. Optical mapping
Voltage-sensitive dye
Sock Electrode Array (125 bipolar electrodes)
2D
3D
RV
Apex
LAD
LV
Global epicardial mapping of VT
Isochronal map
Sock electrode array
(Global Epicardium)
RV
RV
Apex
LAD
Apex
LV
LV
Early site
Plague Electrode Array (480 bipolar electrodes)
3.8 cm
3.2 cm
Dog heart
Computerized Electrical Mapping
showing the propagation of cardiac activation
A (3867)
B (3882)
D (3917)
E (3942)
C (3902)
F(fiber orientation)
RV
LV
Conduction block, wavebreak,
and the initiation of VF during rapid pacing
A (1252)
B (1272)
C (1292)
D (1297)
E (1307)
F (1322)
G (1342)
H (1432)
I(fiber orientation)
RV
LV
Cardiac Wedge Preparation
Optical mapping of the origin of ventricular automaticity
Optical Map
(Transmural Section)
Endo
Epi
Early site
Mapping area
x
y
300 ms
epi
PM
endo
1 cm
a. 0 ms
b. 3 ms
c. 8 ms
d. 11 ms
e. 21 ms
f. 51 ms
g. 71 ms
h. 91 ms
y
x
Section 3
Surface ECG
Normal human
Surface ECG
P wave: Atrial (left and right) activation
Amplitude: <0.25mV; Duration: 0.08-0.11sec
P-R interval: Atrial activation time + A-V conduction time
Duration: 0.12-0.20sec
QRS complex: ventricular depolarization
S-T segment: all the ventricular cells are activated.
upward shift:
downward shift:
T wave: ventricular repolarization
Ta wave (atrial T wave): atrial repolarization
merged in QRS
Q-T interval: ventricular activation time (depol + repol)
U wave: mechanism and significance unkown
How surface ECG forms?

ECG leads
(1)Bipolar limb leads (Standard leads): measure
the potential difference between two points.
Lead I:
left arm (+) —— right arm (－)
Lead II: left leg (+) —— right arm (－)
Lead III: left leg (+) —— left arm (－)
If the three limbs of Einthoven‘s triangle (assumed to be equilateral) are broken apart,
collapsed, and superimposed over the heart, then the positive electrode for lead I is said to
be at zero degrees relative to the heart (along the horizontal axis) (see figure
below). Similarly, the positive electrode for lead II will be +60º relative to the heart, and
the positive electrode for lead III will be +120º relative to the heart. This new construction
of the electrical axis is called the axial reference system. With this system, a wave of
depolarization traveling at +60º produces the greatest positive deflection in lead II. A wave
of depolarization oriented +90º relative to the heart produces equally positive deflections in
both lead II and III. In this latter example, lead I shows no net deflection because the wave
of depolarization is heading perpendicular to the 0º, or lead I, axis.
“爱氏三角”
(2) Unipolar limb leads
The combination of the electrodes of left
arm, right arm and left leg show roughly
a zero potential, this point is called
central reference point (中心电端）

Unipolar limb leads (单极肢体导联）：measure the
true potential of a point on the body surface, include:
VR, VL, VF（No more used）
 Augmented Limb Leads (Unipolar) (加压单极肢体导
联）:
3 resistances are loaded, the central reference point
is “really” zero.
aVR, aVL, aVF
The axial reference system
The aVL lead is at -30º relative to the lead I axis; aVR is at -150º and aVF
is at +90º. The six limb leads of the ECG record electrical activity along
the frontal plane (冠状面) relative to the heart. Using the axial reference
system and these six leads, it is simple to define the direction of an
electrical vector at any given instant in time. If a wave of depolarization
is spreading from right-to-left along the 0º axis, then lead I will show the
greatest positive amplitude. If a wave of depolarization is moving from
left-to-right at +150º, then aVL will show the greatest negative deflection,
etc.
(3) Chest leads (Unipolar): V1-V6
These are six positive electrodes placed on the surface of the chest
over the heart in order to record electrical activity in a plane
perpendicular to the frontal plane (figure). A wave of depolarization
traveling toward a particular electrode on the chest surface will elicit
a positive deflection.
Membrane polarization hypothesis of ECG interpretation
（ECG形成的膜极化学说）
Cell polarizes at resting condition,
no potential difference exits
between different sites
Cell is depolarizing (activating),
just like electric dipole(电偶极子）
movement. source
sink
During cell depolarizing,
Electrode at the negative side
records a downward deflection,
and an upward deflection,
vice versa.
During cell repolarizing,
The source is behind the
sink, the electrodes record
deflections in opposite
directions vs depolarization.
Volume Conductor Principles of ECG Interpretation
（ECG形成的容积导体原理）
The body acts as a conductor of the
electrical currents generated by the
heart, it is possible to place electrodes
on the body surface and measure
cardiac potentials.

Cardiac tissue at resting state
 By convention, a wave of
depolarization heading toward the
positive electrode is recorded as a
positive voltage (upward deflection in
the recording).
Cardiac tissue partially excited
 What is volume conductor?
If you put a cell (电池）into the center of a container filled
with salt solution, the solution will be charged and become
a volume conductor. The nearer a point away from the
positive pole, the higher the potential is. The potential at a
given point can be calculated by the equation:
V = E (cos /r2)
(V, voltage. E, electromotive force)
V
r
A

B
 Similarly, the body is a volume conductor, the heart is
like an Electric dipole (电偶极子) during activation. it is
possible to place electrodes on the body surface and
measure cardiac potentials.
 Vector (矢量，向量） is a physical variance which shows both
quantity (intensity or length) and direction, for example, the
mechanical force, electrical current, etc.
 The parallel quadrangle law of the resultant
(合力的平行四边形法则）
 Vectorcardiogram (向量心电图，心电向量图）depicts changes
in current vector length and direction at different times during the
cardiac cycle.
 Sequence of ventricular depolarization and QRS complex
 Sequence of myocardial activation and vector ring
 Key point:
The ECG recorded by each of the six limb leads is the
projection of the frontal vector ring on the respective
lead axis.
(六个肢体导联所记录的心电图是额面向量环在各导
联上的投影)
 Vector rings:
1. P vector ring
2. QRS vector ring
3. T vector ring
Normal QRS and T vector rings
QRS and T vector rings
in cardiac hypertrophy
What will happen if heart rate is too fast?
1. Decrease in cardiac output
2. Instability of cardiac electrophysiology, VF
3. Heart failure
Epicardiogram
HR 200 bpm
Periodic
HR 300 bpm
Alternance
HR 333 bpm
VF
Period doubling bifercation and chaos during rapid pacing
6
0
A
VF
4
0
CL-PI (ms)
2
0
0
2
0
4
0
6
0
8
0
1
0
0
1
2
0
1
4
0
3
2
0
3
0
0
2
8
0
2
6
0
2
4
0
2
2
0
2
0
0
1
8
0
1
6
0
Pacing Interval (ms)
B
Pacing Interval (ms)
301
297
303
300
300
250
220
200
207
190
180
(VF)
500ms
172
205
176
Period doubling bifurcation and chaos
Period-doubling bifurcation to chaos during rapid
pacing 6
0
室颤
4
0
△
2
0
Cycle Length (ms)
0
2
0
4
0
6
0
8
0
1
0
0
1
2
0
1
4
0
3
2
0
3
0
0
2
8
0
2
6
0
2
4
0
2
2
0
2
0
0
1
8
0
1
6
0
Pacing Interval（ms）
心率加快时出现的激动周期倍增和VF的诱发
0
0
CL 4
3
8
0PCL 300ms
(ms) 3
6
0
3
4
0
规则模式（正常）
3
2
0
2
8
0
2
6
0 PCL 190ms
2
4
0
2
2
0
2
0
0
3
0
0
1
8
0
2
8
0
1
6
0
2
6
0
1
4
0
2
4
0
1
2
0
2
4
6
8
1
0
1
2
1
4
1
6
1
8
0
2
4
6
8
1
0
1
2
1
4
1
6
1
8 0
ABAB模式（交替）
2
0
0
2
6
0
1
8
0PCL 160ms,
2
4
0 PCL 170ms
1
6
0
2
2
0
1
4
0
2
0
0
1
2
0
1
8
0
1
0
0
1
6
0
8
0
1
4
0
6
0
1
2
0
4
0
1
0
0
5
1
0
1
5
2
0
2
5
3
0
3
5
4
0
0
2
4
6
8
1
0
1
2
1
4
1
6
1
8 0
ABCDABCD模式
Cycle Number
VF
浑沌（chaos）
2
8
0
2
6
0
室速向室颤转化时的倍周期分岔和浑沌现象
2
4
0
1. 规则心跳
2. 交替节律 (ABAB模式）
2
2
0
(心率 200 BPM)
(心率 300 BPM)
2
0
0
激动周期
1
8
0
2
0
0
1
8
0
1
6
0
1
6
0
1
4
0
1
4
0
3. ABCDABCD模式
4. 浑沌(chaos), 室颤
1
2
0
(心率 333 BPM)
(心率 316 BPM)
1
2
0
2
4
6
8
1
0
1
2
1
4
1
6
1
8
1
0
0
0
2
4
6
8
1
0
1
2
1
4
1
6
1
8
8
0
6
0
4
0
0
5
1
0
1
5
2
0
2
5
3
0
3
5
4
0
Variety of phase-4 bifurcation of RR interval
1
6
2
4
0
240
?
220
270
2
3
0
2
6
0
260
2
0
0
200
2
2
0
2
5
0
250
2
1
0
8
0
1801
2
4
0
240
2
0
0
200
YDat
YDat
YDat
2
3
0
230
1
9
0
6
0
1601
2
2
0
220
1
8
0
180
1
7
0
A
4
0
1401
2
1
0
210
C
B
6
7
2
c
h
1
7
1
6
0
2
0
0
2
0
160
200
1201
0
2
4
6
8
1
0
1
2
1
4
1
6
1
8
0
2
4
6
8
1
0
1
2
1
4
1
6
1
8
0
2
4
6
8
1
0
1
2
1
4
1
6
1
8
0 2 4 6 8 10 12 14 16 18
0 2 4 6 8 10 12 14 16 18
0 2 4 6 8 10 12 14 16 18
6
7
6
c
1
0
5 7
2
3
1
9
0
c
h
2
0
X
D
a
t
a
X
D
a
t
a
2
6
0
260
220
2
4
0
240
2
5
0
250
0
0
2002
2
2
0
220
2
4
0
240
X
D
a
t
a
2
2
0
260
2
6
0
8
0
1801
200
YDat
YDat
2
0
0
YDat
Activation Cycle Length (ms)
220
6
7
2
c
1
9
2
2
0
2
7
0
2
3
0
240
6
0
1601
1
8
0
180
2
2
0
220
4
0
1401
1
6
0
160
E
D
F
1
4
0
2
1
0
2
0
210
140
1201
0
2
4
6
8
1
0
1
2
1
4
1
6
1
8
0
2
4
6
8
1
0
1
2
1
4
1
6
1
8
0
2
4
6
8
1
0
1
2
1
4
1
6
1
8
0 2
4 6 8 10 12 14 16 18
0 2 4 6 8 10 12 14 16 18
0 2
4 6 8 10 12 14 16 18
X
D
a
t
a
X
D
a
t
a
Cycle #
X
D
a
t
a
Conduction velocity alternans and VF during rapid pacing
1
0
0
9
0
传导速度
(CV)
1
0
0
PI 300ms
2
D
G
r
a
p
h
4
2
D
G
r
a
p
h
3
2
D
G
r
a
p
h
7
9
0
1
0
0
PI 250ms
9
0
8
0
8
0
8
0
7
0
7
0
7
0
6
0
6
0
6
0
5
0
5
0
5
0
4
0
4
0
4
0
3
0
3
0
3
0
2
0
2
0
2
0
1
0
1
0
0
024681
0
1
2
1
4
1
6
1
8
2
0
1
0
0
9
0
1
0
2
D
G
r
a
p
h
6
0
024681
0
1
2
1
4
1
6
1
8
2
0
1
4
0
PI 200ms
1
3
0
8
0
1
2
0
7
0
1
1
0
6
0
1
0
0
5
0
9
0
4
0
8
0
3
0
7
0
2
0
6
0
1
0
5
0
0
0
2
4
6
8
1
0
1
2
1
4
1
6
1
8
2
0
PI 220ms
PI 180ms
VF
4
0
02468
1
0
1
2
1
4
1
6
1
8
2
0
连续心跳
0
0
2
4
6
8
1
0
1
2
1
4
1
6
1
8
2
0
Conduction Time (ms)
CV period-doubling and VF during rapid pacing
100
100
80
80
60
60
40
40
20
20
0
0
0
2
4
6
8
10
12
14
16
18
20
0
100
140
80
120
60
100
40
80
20
60
2
4
6
8
10
12
14
16
18
20
18
20
VF
40
0
0
2
4
6
8
10
12
14
16
18
20
0
Cycle #
2
4
6
8
10
12
14
16
心率逐渐加快时CL的时间和空间交替及VF的形成
CL-PI (ms)
PI (ms)
300
15
200
-15
15
190
-15
15
-15
-10
180
(VF)
-50
#15
#16
#17
Number of Cycle Length
#18
心率逐渐加快时CL的时间和空间交替及VF的形成
（计算机模拟）
PI(ms)
CL-PI (ms)
1.0
1.0
300
BCL=300 ms
A
-1.0
-1.0
5.0
5.0
200 ms
200
-5.0
-5.0
8.0
8.0
190 ms
190
-8.0
-8.0
15.0
15.0
185 ms
185
-15.0
-15.0
100.0
180 ms
(VF)
100.0
180
(VF)
-100.0
-100.0
#1
#2
#3
Number of Cycle Length
#4
R wave oscillation and VF during rapid pacing
PI (ms)
300
200
190
180
170
VF
160
The first captured beat
1000 ms
APD restitution curve
Slope=1
240
220
APD (ms) 200
180
Y =-3.3617 + 41.4293 * LN(X)
160
140
0
50
100
150
200
250
300
350
DiastoIic Interval (ms)
400
APD restitution curve：决定激动的时间不均一性
斜率<1
致室颤
150
100
抗室颤
50
0
50
100
150
斜率>1
200
APD (ms)
APD (ms)
200
150
100
50
0
200
40
80
舒张期 (ms)
120
160
200
舒张期 (ms)
CV restitution curve：决定激动的空间不均一性
斜率>1
斜率<1
0.5
致室颤
0.4
抗室颤
0.3
0
50
100
150
舒张期 (ms)
200
CV (m/s)
CV (m/s)
0.5
0.4
0.3
0
50
100
150
舒张期 (ms)
200
6
0
VF
4
0
2
0
CL-PI (ms)
0
2
0
ERP (ms)
4
0
PI 600 550
6
0
500
240
450
400
200
300 280
240
260
220
8
0
1
0
0
1
2
0
220
350
180
160
190
400 350 300 250 200 150 100 50
140
0
DI (ms)
1
4
0
3
2
0
3
0
0
2
8
0
2
6
0
2
4
0
2
2
0
2
0
0
1
8
0
1
6
0
Pacing Interval (ms)
心率很快时出现的传导阻滞、激动波阵面分裂和VF
A (1252)
B (1272)
C (1292)
D (1297)
E (1307)
F (1322)
G (1342)
H (1432)
I(fiber orientation)
RV
LV
B. Electrograms
A. Isochronal maps during pacing
Activation Time (ms)
Captured Beats
Beat No.
#16
#17
#18
1
#19
2
3
4
5
6
VF
7 8
PI 300 ms
Pacing artifacts
#1
#2
#3
#4
PI 160 ms
Induction
of VF
1
#5
#6
#7 (VF)
2
Cycle No.
PI 160 ms
Induction
of VF
#1
#2
4
5
6
7
8
VF
Captured Beats
#8 (VF)
1
C. Iso-deviation maps of CL
3
2
3 4
5
6
VF
Cycle Length Variation (activation CL-PI, ms)
#3
#4
#5
#6
#7
#8