Unit Four

Circulation

Right AtriumPulmonary Artery

Vena cava

Aorta

Pulmonary capillary

Right Ventricle

Left atriumLeft ventricle Pulmonary

vein

Systemiccapillary

The cardiovascular system consists of the heart and blood vessels

Tissue fluid circulation

Blood circulation Lymph circulation

(Power)

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

Arterial valves

Venous valves

Lymphatic valves

Bicuspid valve (Mitral valve)

Tricuspid valve

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

Cardiac Physiology

Excitation & conduction （ Electrical activity ）

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

atrial-nodal zone

nodal zone

nodal-His zone

His bundle

internodal pathways

AV node

The structure of AV node

心房肌

希氏束 浦氏纤维

心室肌

窦房结

房室结

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

Figure 9-6 ICal in ventricular cell

Figure 9-7 IKr and IKs in dog ventricular cell

I Kr

I Ks

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 inactivation

excitable excitated non-excitable

ARP, ERP

(2) The distance between resting potential (maximal d

iastolic 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 an

d

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 block1st 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

Apex

RV

LV

LAD

Sock Electrode Array (125 bipolar electrodes)

2D 3D

RV

LV

Apex

Early site

Isochronal map (Global Epicardium)

Apex

RV

LV

LAD

Sock electrode array

Global epicardial mapping of VT

3.2 cm

3.8

cm

Plague Electrode Array (480 bipolar electrodes)

Dog heart

Computerized Electrical Mapping showing the propagation of cardiac activation

B (3882) C (3902)

E (3942)

A (3867)

D (3917) F(fiber orientation)

Septum

RVRV

LV

G (1342)

A (1252)

H (1432)

B (1272)

D (1297) E (1307)

C (1292)

I(fiber orientation)

Septum

RV

LV

F (1322)

Conduction block, wavebreak, and the initiation of VF during rapid pacing

Cardiac Wedge Preparation

Mapping area

Epi

Early site

Optical Map (Transmural Section)

Endo

Optical mapping of the origin of ventricular automaticity

a. 0 ms b. 3 ms c. 8 ms d. 11 ms

PM

endo

1 cm

epie. 21 ms f. 51 ms g. 71 ms h. 91 ms

xy

300 ms

x

y

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 t

he 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.  

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.

Membrane polarization hypothesis of ECG interpretation（ ECG 形成的膜极化学说）

During cell repolarizing,The source is behind the sink, the electrodes record deflections in opposite directions vs depolarization.

　 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.

By convention, a wave of depolarization heading toward the positive electrode is recorded as a positive voltage (upward deflection in the recording). 

Volume Conductor Principles of ECG Interpretation（ ECG 形成的容积导体原理）

Cardiac tissue at resting state

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)

A B

r

V

Similarly, the body is a volume conductor, the heart is li

ke an Electric dipole ( 电偶极子 ) during activation. it is p

ossible to place electrodes on the body surface and measur

e cardiac potentials.

Vector ( 矢量，向量） is a physical variance which shows both

quantity (intensity or length) and direction, for example, the mecha

nical 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 change

s 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 333 bpmVF

HR 200 bpmPeriodic

HR 300 bpmAlternance

Pacing Interval (ms)

CL-

PI

(ms)

300

250

220

200

190

180(VF)

Pac

ing

Int

erva

l (m

s)

301 297 303 300

207 172 205 176

VFA

B

500ms

Period doubling bifercation and chaos during rapid pacing

Period doubling bifurcation and chaos

Period-doubling bifurcation to chaos during rapid pacing

室颤

Pacing Interval （ ms ）

△ Cycle Length

(ms)

Cycle Number

PCL 300ms PCL 190ms

PCL 170ms PCL 160ms, VF

规则模式（正常） ABAB 模式（交替）

ABCDABCD 模式 浑沌（ chaos ）

CL(ms)

心率加快时出现的激动周期倍增和 VF 的诱发

室速向室颤转化时的倍周期分岔和浑沌现象

1. 规则心跳 ( 心率 200 BPM)

2. 交替节律 (ABAB 模式） ( 心率 300 BPM)

3. ABCDABCD 模式 ( 心率 316 BPM)

4. 浑沌 (chaos), 室颤

激动周期

( 心率 333 BPM)

0 2 4 6 8 10 12 14 16 18

160

180

200

220

240

A

0 2 4 6 8 10 12 14 16 18

240

250

260

240

220

210D

0 2 4 6 8 10 12 14 16 18

160

200

180

220

260

140

240

0 2 4 6 8 10 12 14 16 18120

140

160

180

200

220

C

0 2 4 6 8 10 12 14 16 18

220

200

180

160

140

120FE

0 2 4 6 8 10 12 14 16 18

260

240

220

200B

210

230

250

270

Cycle #

Act

ivat

ion

Cyc

le L

engt

h (m

s)Variety of phase-4 bifurcation of RR interval

PI 300ms PI 250ms PI 220ms

PI 200ms PI 180ms

VF

传导速度 (CV)

连续心跳

Conduction velocity alternans and VF during rapid pacing

CV period-doubling and VF during rapid pacing

Cycle #

Con

duct

ion

Tim

e (m

s)

VF

PI (ms)

Number of Cycle Length

300

200

190

#15 #16 #17 #18

180(VF)

15

-1515

15-15

-15-10

-50

CL-PI (ms)

心率逐渐加快时 CL 的时间和空间交替及 VF 的形成

100.0

-100.0

15.0

-15.0

8.0

-8.0

5.0

-5.0

1.0

-1.0A

Jinmin Cao, FIG.1

(VF)180 ms

185 ms

190 ms

200 ms

BCL=300 ms1.0

-1.0

5.0

-5.0

8.0

-8.0

15.0

-15.0

100.0

-100.0

300

200

190

185

180(VF)

PI(ms) CL-PI (ms)

#1 #2 #3 #4

Number of Cycle Length

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）

The first captured beat

300

200

190

180

170

160

PI (ms)

VF

1000 ms

R wave oscillation and VF during rapid pacing

DiastoIic Interval (ms)

APD (ms)

0 50 100 150 200 250 300 350 400

140

160

180

200

220

240

Y =-3.3617 + 41.4293 * LN(X)

APD restitution curve

Slope=1

0 50 100 150 200

0.3

0.4

0.5

CV

(m

/s)

舒张期 (ms)

APD restitution curve ：决定激动的时间不均一性

CV restitution curve ：决定激动的空间不均一性

0 50 100 150 200

50

100

150

200

AP

D (

ms)

舒张期 (ms)

斜率 <1

0 50 100 150 200

0.3

0.4

0.5

CV

(m

/s)

舒张期 (ms)

斜率 <1

0 40 80 120 160 200

50

100

150

200

AP

D (

ms)

舒张期 (ms)

斜率 >1

斜率 >1

致室颤

致室颤

抗室颤

抗室颤

Pacing Interval (ms)

CL-

PI

(ms)

VF

600500

400

300 280240

350

220

190

PI

260

450550

050100150200250300350400

160

140

180

200

220

240

DI (ms)

ERP (ms)

G (1342)

A (1252)

H (1432)

B (1272)

D (1297) E (1307)

C (1292)

I(fiber orientation)

Septum

RV

LV

F (1322)

心率很快时出现的传导阻滞、激动波阵面分裂和 VF

PI 300 ms

#16 #17 #19#18

PI 160 msInduction of VF

#2#1 #3 #4

Beat No.

#6#5 #7 (VF) #8 (VF)

A. Isochronal maps during pacingActivation Time (ms)

B. Electrograms

C. Iso-deviation maps of CL

PI 160 msInduction of VF

Cycle Length Variation (activation CL-PI, ms)

#1 #2 #3 #4Cycle No. #5 #6 #7 #8

Captured Beats

1 2 3 4 5 6VF

1 2 3 4 5 6 7 8

Pacing artifacts

VF

1 2 3 4 5 6 7 8VF

Captured Beats