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Impulse generating and conducting system of the heart
Origin and spread of cardiac excitation:
Shape of electrical activity depends on the
site of recording:
1. From the SA and AV node
→ Pacemaker potentials
2. From the atrial and ventricular
muscle and Purkinje fibers
→ Action potentials
Differences in:
- latency time
- time course
- resting potential
- amplitude
Fast and slow response
Impulse generating and conducting system of the heart
Pacemaker activity:
low resting potential
- leaky membrane to Na
- abscence of Na channels
diastolic depolarization
- IK decreases
- Na and Ca enter
action potential
- ICa increases (rising phase)
- IK increases (repolarization)
Control of heart rate:
tachycardia, bradycardia
Modified by adrenergic and cholinergic innervation
→ slope of diastolic depolarization
→ maximal diastolic repolarization
→ threshold potential of AP
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Impulse generating and conducting system of the heart
Impulse generation:
- physiological pacemaker (nomotopic)
SA node: 70-80/min
- ectopic pacemakers (heterotopic)
AV node: 40-60/min
Purkinje: 20-40/min
Cardiac arrhythmias:
Abnormal pacemaker activity
and /or spread of excitation
Passive: The transmission of impulses is
slowed or blocked in the conductive
system, in most cases at the AV node
Active: extrasystole or fibrillation
1. Reactivation of silent pacemaker cells
2. Abnormal shortening of AP due to
inhomogenous repolarization
3. Re-entry due to unidirectional block
and slower conduction
Impulse generating and conducting system of the heart
Mechanism of the re-entry:
Antiarrhythmic drugs:
I. Blockers of sodium channel
II. Decreasing of sympathetic tone
III. Blockers of repolarization
IV. Blockers of potassium channels
V. Special drugs causing bradycardia
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Impulse generating and conducting system of the heart
Action potentials at atrial and ventricular fibers:
Upstroke (fast depolarization):
- the Na channels open, then inactivate
Plateau (slow repolarization):
- slow Ca channels open
- K and Cl channels open
Repolarization:
- Ca channels close
Frequency dependece of AP duration:
- some of K channels do not close
- more Cl channels open
Impulse generating and conducting system of the heart
Changes in excitability:
absolut refractory period
depolarized membrane
- Na channels inactivated
closed
open
inactivated
- Ca channels open
relative refractory period
partial repolarization
- Na and Ca channels close
The excitability is membrane potential
dependent
The pacemaker cells have longer refractory
periods
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Impulse generating and conducting system of the heart
The time course of AP and contraction of the heart as a pump:
Limits the frequency of AP
extrasystole, compensatory pause
The heart muscle can not be tetanized
fibrillation
Impulse generating and conducting system of the heart
Spread of excitation:
gap junctions
ri is higher by 1%
effects of i.c. Ca2+ and H+, anoxia,
damages
Conduction speeds:
SA node: 0,05 m/s
atrium:
1 m/s
atrial excitation
AV node: 0,05 m/s
nodal delay
slow response
Purkinje:
2-4 m/s
ventricle:
1 m/s ventr. excitation
from endocardial to epicardial
Significance:
the atrial and ventricular excitation is
separeted
the atrial ejection and ventricular
filling is possible
frequency filtering
rectification
all portions of the ventricular muscle
contract at about the same time
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Electrocardiogram
Depolarization waves: P and QRS
Repolarization wave: T
Zero base line:
complete polarization or
complete depolarization
Electrocardiogram
Recording of ECG:
Bipolar limb leads, frontal plane
Einthoven I., II., III.
Unipolar chest leads, horizontal plane
Wilson leads: V1’-V6’
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Contractile properties
The excitation-contraction coupling:
depolarization → i.c. Ca2+↑ → contraction
repolarization → i.c. Ca2+↓ → relaxation
Voltage dependent process
action potential, or depolarization
Contractile properties
Increase of i.c. [Ca2+]:
opening of Ca channels
dihydropyridin receptors (DHPR)
Ca induced Ca release
SR ryanodin receptors (RyR)
Decrease of i.c. [Ca2+]:
SR Ca pump (SERCA)
phospholamban
calsequestrin
Na-Ca exchange
secondary active transport
effect of digitalis
Plasma membrane Ca pump
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Nervous control of the heart
Tonic actions of nerves:
actions:
influences on:
chronotropic
heart rate
inotropic
contractil strength, dP/dt
dromotropic
conduction velocity
bathmotropic
excitability
Nervous control of the heart
Sympathetic nerves:
preganglionic fibers
synapses:
nicotinic Ach receptors
postganglionic fibers
SA and AV node, atria, ventricles
receptor:
β1
mediator:
epinephrine, norepinephrine
agonist:
isoproterenol
antagonist:
propranolol
transduction: G protein, cAMP increases,
protein kinase A
effects:
positive tropic effects
mechanism:
DHPR Ca channels
RyR Ca channels
K channels
troponin I
phospholamban
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Nervous control of the heart
Parasympathetic nerves:
Vagus
dorsal nucleus of the vagus in the medulla
Sympathetic
effect
preganglionic fibers
synapses:
nicotinic Ach receptors
postganglionic fibers
SA and AV nodes, atria
receptor:
muscarinic Ach receptors
mediator:
acetylcholine
agonist:
muscarine
antagonist:
atropine
transduction:
G protein, cAMP decreases,
protein kinase A
effects:
negative tropic effects
mechanism:
DHPR Ca channels, etc.
Effects of extracellular ions (Na+, K+, Ca2+)
Possible changes in:
resting potential
action potential
E-C coupling
Na-Ca exchange
Cardioplegic solution: high [K+], low [Na+]
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Contractile properties
Properties of cardiac muscle cells:
Contraction and relaxation
Systole and diastole
Contractile and elastic elements
Isotonic and isometric contraction
Pressure-volume loop:
Calculation of cardiac work:
W = pa V +1/2 m v2
pressure-volume work +
acceleration work (4-25%)
preload and afterload
Control of the cardiac output
Cardiac output = stroke volume x heart rate
Length-tension relationship:
Methods of measurement:
Fick method
Indicator dilution
Control of the heart rate:
by sympathetic or parasympathetic nerves
Control of the stroke volume:
by changing of the resting length or
by positive inotropic effect
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Control of the cardiac output
Ventricular volume (ml)
Heterometric regulation: A Starling’s law of the heart
Denervated heart (heart-lung preparation)
The ventricular performance is regulated by the
diastolic volume (diastolic reserve) at changes
- in the peripherial resistance, and
- in the venous return
Significance:
- at transplanted heart
- at trained athletes
- at balancing the ejection of ventricles
Homeometric regulation:
by the sympathetic nerves
positive inotropic effect
The ventricular performance is regulated
without changing the resting length,
the end-systolic volume decreases (systolic
reserve)
diastolic reserve
end-diastolic volume
stroke
volume
end-systolic volume
systolic reserve
The cardiac cycle
A-V valves
Location:
Semilunar valves
Between the atrium Between the ventricle
and the ventricle
and the big artery
Left:
Mitral
Aortic
Right:
Tricuspidal
Pulmonary
Sound:
I.
II.
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The cardiac cycle
Phases of the cardiac cycle:
Ventricular systole: izometric contraction
maximal ejection
decreased ejection
Ventricular diastole: izometric relaxation
rapid filling
decreased filling
atrial systole
Heart murmurs
Systolic murmur:
during ventricular systole, between the I. and II. sounds
Diastolic murmur:
during ventricular diastole, between the II. and I. sounds
Narrowed:
stenosis
Incompetent:
insufficiency
semilunar
systolic
diastolic
A-V valve
diastolic
systolic
The valve is
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Contractile activation in heart failure
Applied methods:
Enzymatic isolation of cardiac myocyte
Single cell patch-clamp technic
Fluorescence indicator dyes
Myocyte from patients with heart
failure
Contractile activation in heart failure
Conclusions: SR Ca-ATPase activity is lower
Consequences:
1. resting [Ca2+]i is higher → arrhythmias
2. SR calcium content is lower → small calcium release
3. slow calcium reuptake → prolonged relaxation
Compensation:
Na-Ca exchange can increase
Level of phospholamban decreases
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