electrophysiology of cardiac contraction effect of drug in different phase brief of heart block

1. ELECTROPHYSIOLOGICAL
CONSIDERATION OF CARDIAC
CONTRACTION
Dr Javed Akhtar
JR - 1
Department Of Pharmacology
K.G.M.U, Lucknow

2. OBJECTIVES
• Introduction
• Parts of conducting system
• Spread of conduction
• Cardiac action potential
• ECG
• Brief outline of arrhythmia and Heart block

3. INTRODUCTION
Function of conducting system of heart-
1. Generating rhythmical electrical impulses.
2. Conduction of impulses rapidly through out the heart.
3. Contraction of atria ahead of ventricles.
4. Allow all portions of ventricles to contract
simultaneously which is essential for effective pressure
generation in ventricles chamber.

4. Conducting System Of Heart

5. SA NODE (Sinoatrial node)
• Location:- superior posterolateral wall of right atrium
immediately below and slightly lateral to opening of the
superior vena cava.
• Pacemaker of heart because its rate of rhythmical
discharge is faster than that of any other part of the heart.
• The SA node fibers connect directly with the atrial muscle
fibers, so that any action potential that begins in the SA
node spreads immediately into the atrial muscle wall.

6. SA NODE
• Nerve supply:- Right vagus
• Blood supply:- 65% cases right coronary artery
35% cases left coronary artery
• Rate of impulse generation:- 70- 80/ min (max.)
• Conduction velocity:- 0.05 seconds

7. Internodal bundles of atrial
• Spreads action potentials originating in the sinus node to
the entire atrial muscle mass and, eventually to the A-V
node.
• Bachmann bundle is branch of anterior internodal fibres
that passes through anterior wall to right atrium to left
atrium.
• Other small band from anterior, lateral and posterior
atrial walls terminate in AV node are called respectively
the anterior, middle, posterior internodal pathway.

9. A-V NODE (Atrioventricular node)
• A-V node is located in the posterior wall of the right atrium
immediately behind the tricuspid valve.
• It is known as gatekeeper of the heart, because its regulate
the impulses coming from SA node.
• Nerve supply:- left vagus
• Blood supply:- right coronary artery
• Rate of impulse generation:- 40-60/ min
• Conduction velocity:- 0.02 to 0.05 m/sec.
Conduction velocity of AV node is least because of:
• less number of gap junctions
• slow type of action potential
• small fibre diameter

10. Part of conducting
system
Reason for delay Duration(sec)
Internodal pathways Transmission time 0.03 sec
AV node Less number of gap
junction
0.09 sec
AV bundle Resistance in AV
bundle
0.04 sec
AV nodal delay
A total delay of 0.16 sec. This allows time for the atria to
empty their blood into ventricles before ventricular
contraction begins.
This increases efficacy of the pumping action of heart.

11. The A-V node is continuous with the bundle of His which
give off a left bundle branch at the top of the interventricular
septum and continue as right bundle branch.
The left bundle branch further divides into the left anterior
and the left posterior fascicles.
These bundles and fascicles runs subendocardially down
either side of the septum and come in contact with Purkinje
fibers. These fibers distribute the impulse to the ventricular
muscle.

12. • The Purkinje fibers (Subendocardial branches)are
located in the inner ventricular walls of the heart, just
beneath the endocardium in a space called the
subendocardium.
• Help in conduction system to create synchronized
contractions of its ventricles.
• Maximum gap junction are present in purkinje fibres.
• Also have very few myofibrils, so contract little or not at
all during impulse transmission.
• Rate of impulse generation:- 15-40/ min.
• Conduction velocity: 4 m/s (max.)

13. Tissue Discharge rate(beats /min)
SA node 70 - 80(max. up to 100)
A-V node 40 - 60
His bundle
Purkinje fibres 15 - 40
Discharge rate of various tissue

14. Tissue Rate(m/sec)
SA node 0.05
Atrial pathways 1
A-V node 0.02 to 0.05
Bundle of His 1
Purkinje fibers 4
Ventricular muscles 1
Conduction speed of impulse

15. Spread of Cardiac Excitation
• Atrial depolarization: starts at SA node
• Atrial repolarization: also starts at SA node
• Ventricular depolarization:
– Endocardial surface of IVS of left ventricle than right
endocardial.
– It then passes down and through the purkinje system,
depolarizes ventricles simultaneously from
endocardium to epicardium.
– Top most portion of IVS septum and posterobasal
epicardial surface of left ventricle are last.
• Ventricular repolarization: the apical epicardial surface
is first, the base endocardial surface is last to repolarizes.

16. The Cardiac Action Potential
Cardiac action potential differ from other by two major ways:
1. Duration of action potential
– AP duration of nerve is about 1 ms
– AP duration of skeletal muscle is 2-5 ms
– In contrast cardiac AP duration is 200 to 400 ms
2. Role of calcium ions in depolarization
– In cardiac pacemaker cells, calcium ions are involved in
the initial depolarization phase of the action potential.
– In non pacemaker cells, calcium influx prolongs the
duration of the action potential and produces a
characteristic plateau phase.

17. • Channels that play important role in cardiac AP:
– Sodium channels:
• Open for very few 10000th of second.
• Responsible for rapid upstroke spike of AP in ventricular
muscles.
– Calcium channels:
• Responsible for plateau phase of ventricular cells (L-type
channels).
• Responsible for pacemaker cells depolarization (L-type
channels).
• Responsible for pacemaker potential (T-type channels)
– Potassium channels:
• Outward diffusion of K⁺.
• Responsible for restoring of AP.
• Restoring RMP.

18. Fast response AP Slow response AP
Occurs in Atrial and ventricular
myocytes and purkinje fibers
SA and A-V node
Phases Five phases:
Depolarization (phase 0):
rapid
Early repolarization (phase 1)
Plateau(phase 2)
Repolarization(phase 3)
RMP(phase 4)
Three phases
Depolarization (phase 0): slow
upstroke
phase 1 absent
phase 2 may be short or absent
Repolarization(phase 3)
RMP(phase 4): also known as
prepotential or pacemaker
potential phase
RMP Myocytes: -90 mV
Purkinje fiber: -80 mV
SA node: -55 mV
AV node: -60 mV
Max.
amplitude of
phase 0
+20mV +10 mV

20. Depolarization (phase 0)
• Na⁺ enters through specific fast voltage activated
channels.
• Na⁺ channels activate very rapidly(about 0.1 sec).
• Once open, inactivate very rapidly(about 1 to 2 msec).
• Na⁺ channel in inactivated state, they cannot be
reopened and another AP cannot be generated, this is
absolute refractory period.

21. Early Repolarization(phase 1)
• Efflux of K⁺ from the cell(main).
• Closure of fast Na⁺ channel.
• This repolarization is brief because of activation of a
transient outward current(ito) carried mainly by K⁺.
• Ito is rapidly activated and deactivated.
• Once activated, K+ ions from inside the cells flow to the
extracellular space.
• This outward flow of positively charged ions constitutes
the Ito and causes the transmembrane voltage to
decrease.
• This decrease of the transmembrane potential is known
as repolarization. Ito is then quickly deactivated, stopping
the repolarization and ending the phase 1.

22. Plateau (phase 2)
• Ca⁺⁺ enter myocardial cells via voltage regulated L-type
Ca⁺⁺ channels.
• This excess Ca⁺⁺ decrease permeability of K⁺ and there
by prevent early return of AP to resting level.
• Ca⁺⁺ is slowly counter balanced by efflux of K⁺.
• K⁺ exits mainly through delayed rectifier(ik)

24. Repolarization(phase 3)
• Efflux of K⁺ from cardiac cell begins to exceed influx of
Ca⁺⁺.
• Three outward K⁺ currents(ito, ik, ik1) contribute to final
repolarization.
• Transient and delayed rectifier help initiate repolarization.
• Inward rectifier (ik1)does not participate in initiation, its
contribute substantially to rate of repolarization once
phase 3 initiated.
• Help in maintaining a more prolonged cardiac action
potential.
• At this phase, inactivated Na⁺ begin transition to closed
state, this period is called relative refractory period.

25. RMP (Phase 4)
• Restoration of Na⁺ and K⁺ are done by
Na⁺-K⁺-ATPase.
• 3 Na⁺-1Ca⁺⁺ antiporter eliminated most of the excess
Ca⁺⁺ ions that had entered in phase 2.

26. Slow response AP

27. Slow response action potential
Phase 4/prepotential/pacemaker potential
• The pacemaker potential is what drives the self-
generated rhythmic firing (automaticity) of pacemaker
cells.
1. Inward funny current(i): main current carried by slow
type Na⁺ channel. This channel is activated as the
memb. potential hyperpolarized beyond  50 mV.
2. Inward calcium current: via transient, rapid T type Ca⁺⁺
channel.
3. Decrease outward K⁺ current: reduced K⁺ permeability
along with increase permeability of Na⁺ and Ca⁺⁺ causes
prepotential.

28. Depolarization(phase 0)
• slow upstroke.
• Due to influx of Ca⁺⁺ through L-type Ca⁺⁺ channels.
Repolarization(phase 3)
• Inactivation of Ca⁺⁺ channels.
• Increase K⁺ permeability, K⁺ moves in.

29. Hyperpolarization
• Continuation of K⁺ efflux below the threshold of AP and
take the potential to -55 to -60 mV.
• Also cause inward leak of Na⁺ ion which outbalance K⁺
efflux.
• Inward Na⁺ leak take the potential upward to reach the
threshold level and AP generated.
• Since this inward leak of Na⁺ is during hyperpolarization
rather than depolarization, these channels are called as
“funny” channels.

30. DEPOLARIZATION
REPOLARIZATION
HYPERPOLARIZATION
PREPOTENTIAL

31. Action potential in Pacemaker Cells Action potential in Myocardium
•Prepotential :
Slow Na⁺(funny channels)
Ca²⁺ influx (through T-type
Ca²⁺ channels)
Decrease in K⁺ efflux
•Action potential :
Depolarization(phase 0):
increase in Ca²⁺ influx through L
type Ca²⁺ channel
Repolarization(phase 3):
increase in K⁺ efflux
Phase Name Cause
0 Initial rapid
depolarization
and overshoot
Opening of Na⁺
Channels
1 Initial rapid
repolarization
Efflux of K⁺
Closure of Na⁺
channels
2 Plateau Ca²⁺ influx (L
type)
and K⁺ efflux .
3 Repolarization Closure of Ca²⁺
channels
K⁺ efflux
through various
type of K⁺
channels
4 Resting
membrane
potential

32. Nerve Supply Of Heart
• Parasympathetic (vagal)
– Supply atria only
• Rt. Vagus supplies SA node Sinus bradycardia
• Lt. Vagus supplies AV node slows AV conduction
• Acetylcholine acts on heart via activation of K⁺ channels.
• Memb. become hyperpolarized, decrease slope of
prepotential.
• Action mediated via M₂ muscarinic receptor.
• Negative chronotropic
• Negative dromotropic

33. • Sympathetic
– Innervate both atria and ventricles.
– Most sympathetic fibres come from stellate ganglion.
• Norepinephrine bind to β₁ receptors, and facilitates opening
of L-type Ca⁺⁺ channels.
• Speed the depolarizing effect of hyperpolarized Na⁺ channel
• Stimulation of Rt. increases HR(increase SAN discharge)
• Stimulation of Lt. shortens AV conduction time &
refractoriness(decrease AV nodal delay)
• positive chronotropic effect
• positive inotropic effect
• positive dromotropic effect

34. Effects Of Drugs On AP
DRUGS EFFECTS
Sodium channel blocker Reduce slope of AP.
Decrease conduction through atrial and ventricular
muscle.
Beta receptor blocker Reduce Na⁺-Ca⁺⁺ entry in the SA and AV nodes
Slows conduction.
Reduces heart rate.
Potassium channel
blocker
Prolongation of AP duration by increasing
repolarization.
Calcium channel
blocker
Decrease rate of phase 4 depolarization in SA and
AV node.
Decrease plateau phase of AP.

35. ECG
Wave/interval Physiological correlates Duration
(sec)
P wave Atrial depolarization 0.1
PR interval Time between start of atrial
depolarization to ventricular
depolarization
0.12-0.2
PR segment AV delay 0.09
QRS wave Ventricular depolarization 0.08-0.10
ST segment Complete depolarization
T wave Ventricular repolarization 0.27
QT interval Duration of ventricular contraction 0.4

37. Mechanism Of Arrhythmia
• Abnormal impulse formation
1. Ectopic pulse
2. After depolarization
a) Early after depolarization
b) Delayed after depolarization
• Abnormal impulse conduction
1. Reentry e.g PSVT, WPW syndrome
2. Conduction block e.g sick sinus syndrome

38. AFTERPOLARIZATION
• Secondary depolarization that occur during
repolarization that interrupt phase 2,3 and 4.
• This lead to cardiac arrhythmias
– Early :- phase 2 and phase 3
– Delayed :- phase 4

40. HEART BLOCK
 SAN BLOCK
 AVN BLOCK
• Incomplete heart block
• First degree AV block
• Second degree AV block
• Complete heart block
 BBB
• RBBB: RV contract after LV
• LBBB: LV contract after RV
a) Lt. anterior hemiblock
b) Rt. anterior hemiblock

42. • Wolff–Parkinson–White syndrome (WPW): The underlying
mechanism involves an accessory electrical conduction
pathway(bundle of kent) between the atria and the ventricles.
AV nodal delay property is lost. Abnormally fast heartbeat,
palpitation, syncope ,cardiac arrest may occur.
• Stokes–Adams syndrome: sudden transient episodes to
fainting by a reduction in cardiac output due to cardiac
asystole or heart block or arrhythmia resulting in lack of blood
flow to brain.

43. THANK YOU