View
231
Download
0
Category
Preview:
Citation preview
8/11/2019 Chapter 8 Cardiomyocytes
1/48
Chapter 8 From Cardiomyocytes
to Cardiac ConductonBME 501
T. K. Hsiai
8/11/2019 Chapter 8 Cardiomyocytes
2/48
1. General Cellular Morphology
8/11/2019 Chapter 8 Cardiomyocytes
3/48
Muscles
Cardiac muscle is only in the heart and makes up the atria and ventricles (heart walls). Like skeletalmuscle, cardiac muscle contains striated fibers. Cardiac muscle is called involuntary muscle
because conscious thought does not control its contractions. Specialized cardiac muscle cells maintain
a consistent heart rate.
Over 600 skeletal muscles function for body movement through contraction and relaxation of
voluntary, striated muscle fibers. These muscles are attached to bones, and are typically under
conscious control for locomotion, facial expressions, posture, and other body movements. Muscles
account for approximately 40 percent of body weight. The metabolism that occurs in this large mass-produces heat essential for the maintenance of body temperature.
8/11/2019 Chapter 8 Cardiomyocytes
4/48
2. Cardiac Cell Muscle
8/11/2019 Chapter 8 Cardiomyocytes
5/48
8/11/2019 Chapter 8 Cardiomyocytes
6/48
Myocardial fibers are separated from adjacent fibers by their
respective sarcolemmas, the end of each fiber is separated by
dense structures (intercalated discs), that are continuous with
the sarcolemma.anatomic syncytium.
http://faculty.washington.edu/kepeter/118/photos/cardiac_cell1.jpghttp://faculty.washington.edu/kepeter/118/photos/cardiac_cell1.jpghttp://faculty.washington.edu/kepeter/118/photos/cardiac_cell1.jpghttp://faculty.washington.edu/kepeter/118/photos/cardiac_cell1.jpghttp://faculty.washington.edu/kepeter/118/photos/cardiac_cell1.jpghttp://faculty.washington.edu/kepeter/118/photos/cardiac_cell1.jpg8/11/2019 Chapter 8 Cardiomyocytes
7/48
Adherens Junctions
Adherens junctions provide strong mechanicalattachments between adjacent cells.
They hold cardiac muscle cells tightly together as
the heart expands and contracts.
They hold epithelial cells together.
They seem to be responsible for contact inhibition.
Some adherens junctions are present in narrowbands connecting adjacent cells.
Others are present in discrete patches holding the
cells together.
Adherens junctions are built from:
cadherins transmembrane proteins (shown in
red) whoseextracellular segments bind to each other and
whose intracellular segments bind to
catenins (yellow). Catenins are connected to actin
filaments
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/M/Muscles.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CancerCellsInCulture.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/Cytoskeleton.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/Cytoskeleton.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/Cytoskeleton.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/Cytoskeleton.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CancerCellsInCulture.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/M/Muscles.html8/11/2019 Chapter 8 Cardiomyocytes
8/48
Gap Junctions Gap junctions are intercellular channels
some 1.52 nm in diameter. These permit
the free passage between the cells of ionsand small molecules (up to a molecularweight of about 1000 daltons).
They are constructed from 4 (sometimes 6)copies of one of a family of atransmembrane proteins called connexins.
Because ions can flow through them, gapjunctions permit changes in membranepotential to pass from cell to cell.
Example:
The action potential in heart (cardiac)muscle flows from cell to cell through theheart providing the rhythmic contraction ofthe heartbeat.
Cardiac muscle functions as a syncytium
as a wave of depolarization followed bycontraction of the entire myoardium in
Concert (an all-or-none response occurs when
suprathreshold stimulus is applied to any one
focus).
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/U/Units.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/E/ExcitableCells.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/E/ExcitableCells.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/E/ExcitableCells.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/U/Units.html8/11/2019 Chapter 8 Cardiomyocytes
9/48
Sacrolemmal invaginations at the Z-lines are connected with the bulk
interstitial fluid, important for excitation-
contraction coupling.
MitochondriaRapid oxidation of
substrates with synthesis
of ATP for lifetime vs.
skeletal muscles undergo
metabolism anaerobically.
The network of SR consists of
sarcotubules surrounding the
myofibrils transport Ca++.
Colloidal tracer particles
(2-10 nm) do not enter.
SR-Ca++ storage
2.1 Myocyte Internal Structure
8/11/2019 Chapter 8 Cardiomyocytes
10/48
Cardiac or heart muscle resembles skeletal muscle in some ways: it is striated and eachcell contains sarcomeres with sliding filaments of actin and myosin.
Cardiac muscle has a number of unique features that reflect its function of pumpingblood:
The myofibrils of each cell (and cardiac muscle is made of single cells each with asingle nucleus) are branched.
The branches interlock with those of adjacent fibers by adherens junctions. These strongjunctions enable the heart to contract forcefully without ripping the fibers apart.
Cardiac Muscle
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/J/Junctions.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/J/Junctions.html8/11/2019 Chapter 8 Cardiomyocytes
11/48
The Muscle Fiber
The striated appearance of the muscle fiber is created by a pattern of alternatingdark A bands and light I bands.
The A bands are bisected by the H zone
The I bands are bisected by the Z line.
Each myofibril is made up of arrays of parallel filaments.
The thick filaments have a diameter of about 15 nm. They are composed of the protein myosin.
The thin filaments have a diameter of about 5 nm. They are composed chiefly of the protein actin along with
smaller amounts of two other proteins: troponin and tropomyosin.
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/U/Units.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/U/Units.html8/11/2019 Chapter 8 Cardiomyocytes
12/48
Bo-Inspired Micro-Electrostatic actuators
Principle of comb-drive actuation
8/11/2019 Chapter 8 Cardiomyocytes
13/48
Regulation of Muscle Contraction
The main feature of muscle contraction
is the interaction of actin, myosin and ATP.
This fundamental process of contraction is
regulated by the tropomyosin(TM)-troponin-Ca2+
system. According to the current theory, in
the resting muscle TM is positioned in thegroove of the actin double helix in a way
that it sterically blocks the combination of
myosin with actin. This is illustrated in figure, which
shows a thin filament composed
of actin, tropomyosin(TM), TN-C(troponin), TN-I,
and TN-T.
In the absence of Ca2+ (relaxed state), TM blocks the
cross-bridge binding sites on actin. Binding of Ca2+
to TN-C (activated state) initiates the TM movement,
through TN-T, from the center of the actin strand to its
side, thereby releasing the steric blocking. In addition,the TN-C-Ca2+ complex removes TN-I from its
inhibitory position on actin; thus the combination of
the myosin head with actin can proceed to full extent.
Since in the thin filament there is only one TN and
one TM molecule per seven G-actin molecules, one
has to assume that cooperative interactions play a
major role in the regulation of contraction.
8/11/2019 Chapter 8 Cardiomyocytes
14/48
4. Cardiac Muscle Electrical Activity
Length-tension relationship of a single frog semitendinosus
muscle fiber (From Gordon et al., 1966). The numbers 1
through 4 on the length tension curve correspond to the
numbers on the schematic diagram of thick and thin filament
arrangement. In this way the relationship between thick and
thin filaments can be compared to the tension at various
sarcomere lengths.
Crossbridge cycle and its relation to actomyosin ATPase
With a new ATP a new cycle may begin
and the cycling may continue until theregulatory mechanism stops the
interaction of actin and myosin. As
shown in Fig. ME4, ATP is needed for
step 1; that is for the detachment of
myosin from actin. In case of ATP
depletion, the cycle is arrested. When
actin and myosin are permanently bound
in the absence of ATP, the muscle
becomes rigid.
8/11/2019 Chapter 8 Cardiomyocytes
15/48
Length-tension relationship: The physiological interpretation of the sliding filament theory was tested by measuring
the tension of a single muscle fiber at different sarcomere length (Gordon et al., 1966). Figure illustrates the
experiment. Maximum tension was obtained at rest length, between 2.0-2.25 micron, when all crossbridges were
in the overlap region between thick and thin filaments. When the muscle fiber was stretched so that the
sarcomere length increased from 2.25 to 3.675 micron and consequently the number of crossbridges in the
overlap region decreased from maximum to zero; the tension fell from 100% to 0.The crossbridges are uniformly distributed along the thick filaments with the exception of a short bare zone in the
middle. The crossbridges seem to be identical and are the site of the interaction between thick and thin
filaments. The tension is the algebraic sum of the tension produced at each individual site. At or above rest
length the tension is directly proportional to the number of crossbridges in the overlap region between thick and
thin filaments.
Below rest length, when the thin filaments meet in the center of the A band or they start to interact with the
oppositely directed crossbridge sites past the bare zone (in the middle of the sarcomere), tension drops off.
Crossbridge cycle and its relation to actomyosin ATPase: A scheme for the coupling of ATP hydrolysis to the
crossbridge cycle is shown in Figure. The following major steps are involved:
-ATP dissociates actomyosin into actin and myosin; i.e. the thick filaments will be detached from the thin
filaments. ATP binds to the myosin head in the thick filaments.
-ATP is hydrolyzed by myosin; the products ADP and Pi are bound to myosin. The energy released by the
splitting of ATP is stored in the myosin molecule. The myosin.ADP.Pi complex is a high-energy state; this is
the predominant state at rest.-Upon muscle stimulation, the inhibition of actin-myosin interaction, imposed by the regulatory proteins, is lifted
and consequently the myosin with bound ADP and Pi attaches to actin. It is believed that the angle
of crossbridge attachment is 90o.
-The actin-myosin interaction triggers the sequential release of Pi and ADP from the myosin head, resulting in
the working stroke. It is thought that the energy stored in the myosin molecule brings about a
conformational change in the crossbridge tilting the angle from 90o to 45o. This tilting pulls the actin filament
about 10 nm toward the center of the sarcomere, while the energy stored in myosin is utilized.
8/11/2019 Chapter 8 Cardiomyocytes
16/48
4. Cardiac Muscle Electrical Activity
8/11/2019 Chapter 8 Cardiomyocytes
17/48
The Equilibrium Potential is Predictable - The Nernst Equation
The equilibrium described above is predictable with the Nernst equation, which here is given in a form applicable to
cell membranes:
where
Ex is the Nernst potential for ion X (measured as for membrane potentials
inside with respect to outside)
[X]o is the concentration of X outside the cell
[X]i is the concentration of X inside the cell
zx is the valence of ion X
R is the gas constant
T is the absolute temperatureF is Faraday's constant
[X+]o
Vm = 60 log -------- mV
[X+]i
The Nerst Equation for individual ions
8/11/2019 Chapter 8 Cardiomyocytes
18/48
Relative Intra- and Extracellular Concentrations of Some Important Ions
Concentration
Ion Intracellular (mM) Extracellular (mM)
Na+ Low (15) High (145)
K+ High (150) Low (4)
Ca++
low (0.07) high (2)
E (mV)
60
-94
129
8/11/2019 Chapter 8 Cardiomyocytes
19/48
Overall potential: Goldman-Hodgkiom-Katz Equation
Vm is the membrane potential. This equation is used to determine the resting membrane potential in real cells, in which K+,
Na+, and Cl- are the major contributors to the membrane potential. Note that the unit of Vm is the Volt. However, the
membrane potential is typically reported in millivolts (mV). If the channels for a given ion (Na+, K+, or Cl-) are closed, then the
corresponding relative permeability values can be set to zero. For example, if all Na+ channels are closed, pNa = 0.
R is the universal gas constant (8.314 J.K-1.mol-1).
T is the temperature in Kelvin (K = C + 273.15).
F is the Faraday's constant (96485 C.mol-1).
pK is the membrane permeability for K+. Normally, permeability values are reported as relative permeabilities withpK havingthe reference value of one (because in most cells at rest pK is larger than pNa and pCl). For a typical neuron at rest, pK : pNa
: pCl = 1 : 0.05 : 0.45. Note that because relative permeability values are reported, permeability values are unitless.
pNa is the relative membrane permeability for Na+.
pCl is the relative membrane permeability for Cl-.
[K]o is the concentration of K+ in the extracellular fluid. Note that the concentration units for all the ions must match.
[K]i is the concentration of K+ in the intracellular fluid. Note that the concentration units for all the ions must match.
[Na]o is the concentration of Na+ in the extracellular fluid. Note that the concentration units for all the ions must match.
[Na]i is the concentration of Na+ in the intracellular fluid. Note that the concentration units for all the ions must match.
[Cl]o is the concentration of Cl- in the extracellular fluid. Note that the concentration units for all the ions must match.
[Cl]i is the concentration of Cl- in the intracellular fluid. Note that the concentration units for all the ions must match.
Constants
Universal Gas Constant (R) = 8.314 J.K-1.mol-1
Faraday's Constant (F) = 96485 C.mol-1
8/11/2019 Chapter 8 Cardiomyocytes
20/48
Membrane: patch clamping
Biological membranes are fluid mosaics of the lipids and proteins.
The lipids are arranged as bilayers and the proteins are generally free to diffuse laterallyin the lipid matrix. The function of the membranes are mediated by the integral
membrane proteins that serve as channels, receptors, and energy transducers.
Ion channel
8/11/2019 Chapter 8 Cardiomyocytes
21/48
Methods to study cardiac action potential
Electric cardiac cycle
Patch clamping (ion channels) Action potential of skeletal, smooth muscles,and nerves (two electrodes: reference and detection)
a
b c d eERP RRP
Potential
difference= -90 mV
0 mV
Phase 0: rapid
depolarization
Phase 1: partial repolarization
Phase 2: plateau
Phase 3: more negative
repolarization
Phase 4:
Resting state
Overshoot
~20 mV
0.1-0.2 s
Resting state
8/11/2019 Chapter 8 Cardiomyocytes
22/48
SA node (slow
8/11/2019 Chapter 8 Cardiomyocytes
23/48
Atrial and ventricular cells (fast response)
Rapid depolarization
Increased sodium permeability(INa inward current)
Brief repolarizationDue to transient outward current
of potassium ions (Ito)
Plateau phaseA delicate balance between small
inward and outward currents:
Outward current mediated by activation of
Potassium conducting ionic channel (Ik)
Inward current by slow calcium current (I Ca)
Repolarizationto the resting state.
-slow inward Ca++ current
-outward K+ current (I KI)
-Sodium-potassium pump
(Ip=Na+-K+ ATPase pump)
ERP
RRP
Diastolic portionof the action potentialNo spontaneous diastolic
depolarization occurs due to
the activation of K current
(the inward rectifier, I KI)
Threshold level
~-65mV
8/11/2019 Chapter 8 Cardiomyocytes
24/48
8/11/2019 Chapter 8 Cardiomyocytes
25/48
Cardiac action potential
(fast response)
Threshold
~-65 mV
8/11/2019 Chapter 8 Cardiomyocytes
26/48
Nodal cells (slow response)
Phase 0Activation of calcium channel
(Ca++ in flux (ICa++))
Phase 2
Phase 3
Phase 4-In the nodal cells, IKI is not
present
-spontaneous diastolic
depolarization occurs as a
results of the activation of the
pacemaker current (If)
Normal automaticity in the nodal cells is the net result of the absence of Ik1 andthe presence of If.
8/11/2019 Chapter 8 Cardiomyocytes
27/48
Ionic Basis of Action Potential
a) Electrical Phenomena & Ionic Fluxes
Resting Membrane & Action Potentials
there is a concentration (chemical) gradient of ions across the cellmembrane down which ions flow
ion distribution establishes an electrical gradient ie. interior of the cell isnegative relative to the exterior
the distribution of ions across the cell membrane and the nature of thismembrane explain the membrane potential
membrane potential determined by Na+, K+, Ca2+ on either side of themembrane and the permeability of the membrane to each ion
ions diffuse through membranes via ion-specific channels flux of ions controlled by ion-specific "gates"
gates are opened and closed by specific transmembrane conditions(voltage, ionic or metabolic)
8/11/2019 Chapter 8 Cardiomyocytes
28/48
Resting Membrane Potential
the resting membrane potential (steady potential) of cardiac cellsis - 90 mV (ie. inside is negative)
this is maintained by the Na+-K+ ATPase which pumps K+ back into
the cell and keeps intracellular Na+ concentration low passage of electrical current through the membrane leads to
decreases resting membrane potential threshold potential~65 mV
in cardiac muscle cells, stimulation triggers a voltage-dependentincrease in Na+ channels that initiates contraction
this allows cells to generate self-propagating impulses that are
transmitted along their membranes for great distances transmembrane action potential of single cardiac muscle cells is
characterized by rapid depolarization, a plateau, and slowrepolarization
ie. Na+rapidly enters cells at the start of action potential
Ca2+ enters and K+ leaves the cell with each action potential
8/11/2019 Chapter 8 Cardiomyocytes
29/48
ICa
IKI Ca++I Ca++
Ip
If
Nodal cells
8/11/2019 Chapter 8 Cardiomyocytes
30/48
hases of the action potential of a cardiac muscle fiber
1) depolarization proceeds rapidly due to Na+ influx through rapidly openingNa + channels
2) plateau phase is due to Ca2+ influx through more slowly opening
Ca + 2 channels
3) repolarization is due to closure of Ca2+ channels, K+ efflux through K+ channels
4) transmembrane potential and ion gradients are restored by sodium pump
(Na + -K + ATPase=Ip)
One of the K channel is ATP sensitive.The KATP channel normally is inactive during physiologicConditions (the channel is inhibited by ATP under physiologic
Conditions). Under conditions such as ischemia or hypoxia, the
channel is activated when the intracellular ATP concentration
is decreased.
Duration of the action potential is affected
by changes in Ca 2+ and/or K+ conductance
during repolarization. Activation of K+ will
shortened the duration of action potential. But
the duration of activation potential prolonged
when the outward-going K+ are inhibited
digitalis
8/11/2019 Chapter 8 Cardiomyocytes
31/48
8/11/2019 Chapter 8 Cardiomyocytes
32/48
The cardiac action potential
The cardiac action potential is the fundamental unit of electrical activity in the heart. ominant ion
currents that contribute to the action potential in a myocyte from the ventricle are shown in the
previous page.
-Initial depolarization (phase 0) is generated by rapid influx of sodium ions (INa), whose positive
charge depolarizes the membrane toward more positive potentials.
-Once depolarized, the membrane repolarizes transiently due primarily to potassium ion efflux (Ito) toform a notch in the contour of the action potential (phase 1).
-The membrane remains depolarized during the plateau phase (phase 2) , where net current flux is
small, resulting from a near balance of positive charges moving inward (carried predominantly by
calcium ions, ICa, with a smaller component contributed by a persistent sodium influx) and positive
charges moving outward (carried predominantly by two components of the delayed rectifier potassium
current, one that activates rapidly, IKr, and the other that activates slowly, IKs). The inward calcium
current mediates additional calcium release from stores within myocytes and activates the contractile
machinery during mechanical systole. With time, outward potassium currents dominate residual
inward calcium and sodium currents, and the efflux of positive charge allows the membrane to
repolarize to its resting potential (phase 3), from which it is soon ready for the next heartbeat.
-In myocardial cells, such as sinoatrial nodal cells and atrioventricular nodal cells, a pacemaker
current (If) mediates gradual membrane depolarization (phase 4) until a threshold potential is reached
that triggers phase 1 and the ensuing heartbeat.
8/11/2019 Chapter 8 Cardiomyocytes
33/48
Excitation-Contraction Coupling
8/11/2019 Chapter 8 Cardiomyocytes
34/48
Mechanistically, digoxin inhibits the Na/K ATPase pump. Digoxin probably competes with potassium for the K binding site
on the pump. Referring back to the basic physiologic function of a myocardial cell, recall that this pump exchanges
intracellular Na for extracellular K. Also recall that extracellular Na is exchanged for intracellular Ca by a non-energy
dependent facilitated diffusion countertransport mechanism. THEREFORE, if the Na/K pump is inhibited, intracellular Na
will INCREASE. This obliterates the concentration gradient that drives the Na/Ca exchange mechanism. This, in turn,
results in an increase in intracellular Ca. This Ca may then be used to directly or indirectly (by causing the release ofadditional Ca from the SR) cause prolonged excitation-contraction coupling, thereby prolonging the contraction of the
muscle fibres (hence a positive inotropic effect).
The mechanism, illustrated and discussed above, is responsible for the beneficial pharmacodynamic response of positive
inotropy. However, cardiac glycosides possess other pharmacodynamic actions that contribute other effects that may also
influence cardiac function.These agents will stimulate both the adrenergic and vagal neurones that control cardiac function. Stimulation of these
nerves is presumed to result from a similar action on the neurone (inhibition of ATPase). These effects are somewhat dose
dependent, with myocardial tissues affected at low doses, the vagus nerve affected at slightly higher doses, and
sympathetic stimulation not clinical evident until toxic doses are attained.
Recalling the normal physiology of cardiac control, it is evident that stimulation of the vagus nerve at therapeutic doses of
digoxin can result in a negative chronotropic effect, slowing heart rate (bradycardia). Excessive action by this mechanism
can ultimately result in second or third degree heart block that may be characterisic of digoxin toxicity. (Another contributor
to this bradycardia is the effect of digoxin at the AV node specifically, where the refractory period may be prolonged,
delaying impusle conduction from the AV node to the ventricle.)
8/11/2019 Chapter 8 Cardiomyocytes
35/48
Summary
a, Typical action potential (Em), Ca2+ transient ([Ca2+]i),
and calculated INa/Ca reversal potential (ENa/Ca).
b, Curves illustrating how submembrane [Na+]i and
[Ca2+
]i ([Na+
]sm and [Ca2+
]sm) might change during theaction potential owing to local diffusion limitations (note
that [Ca2+]sm may be lower than that in the cleft,
[Ca2+]cleft, as shown in d).
c, INa/Ca calculated by the equation given in ref. 25 as a
function of Em and the indicated concentrations of Ca2+
and Na+. Right panel is expanded in time.
d, Geometry of junctional and submembrane spaces.
http://www.nature.com/nature/journal/v415/n6868/full/415198a.htmlhttp://www.nature.com/nature/journal/v415/n6868/full/415198a.html8/11/2019 Chapter 8 Cardiomyocytes
36/48
Action potential configurations in different regions of the mammalian heart.
Electrocardiogram (ECG)
8/11/2019 Chapter 8 Cardiomyocytes
37/48
g ( )
The electrocardiogram (ECG) is a
technique of recording bioelectric
currents generated by the heart.
Clinicians can evaluate the
conditions of a patient's heart from
the ECG and perform further
diagnosis. ECG records are obtained
by sampling the bioelectric currents
sensed by several electrodes, known
as leads. A typical one-cycle ECG
tracing is shown above.
8/11/2019 Chapter 8 Cardiomyocytes
38/48
SA node (slow
8/11/2019 Chapter 8 Cardiomyocytes
39/48
El i l C di
8/11/2019 Chapter 8 Cardiomyocytes
40/48
Electrical Cardiogram
(ECG/EKG)
ECG
8/11/2019 Chapter 8 Cardiomyocytes
41/48
ECG
An ECG is printed on paper covered with a grid of squares. Notice that five small squares on the paper form a larger square. The width of a single small
square on ECG paper represents 0.04 seconds. The first little hump is known as the P wave. It occurs when the atria depolarize (i.e. trigger). The next
three waves constitute the QRS complex. They represent the ventricles depolarizing. These three are lumped together because a normal rhythm may not
have all three. Many times, you'll only see a R and an S. This is not abnormal. If there are less than three, how do we know which one is which? Well, the
R wave is the first wave ABOVE the isoelectric line. You then name the waves in relation to the R wave. If it falls before the R wave, it is called the Q wave;
after the R wave is the S wave.
An electrocardiogram (ECG) is a record of the electric activity of the heart A
8/11/2019 Chapter 8 Cardiomyocytes
42/48
ECG
The electrocardiogram (ECG or sometimes called EKG) is a record of the heart's electrical activity obtained from a standard set of
body surface electrodes and presented to the physician as the "12-lead ECG": that is, 12 independent graphs of voltage vs. time asobtained from the electrodes.
Current ECG
practice. Although
cardiac activity is
inherently 3-
dimesional, the
current ECG
presents data in
only 2 dimensions,
resulting in loss of
diagnostic
information.
An electrocardiogram (ECG) is a record of the electric activity of the heart. A
standard ECG is produced by sensing electric potentials in six leads from the
limbs (I, II, III, aVR, aVL, aVF) and six leads from the chest (V1-V6).
Electric signals of the heart spread in all directions. However each standard
lead can accurately represent only a small spatial sector around its axis (axes
are shown as green arrows). When projected onto an imaginary sphere
surrounding the heart, such a conic sector would look like a small circle or an
oval.
When an ECG is taken, twelve standard ECG leads may produce normal
tracings (gray ovals) while a pathologic focus (black spot) may remainunnoticed. This happens, because electric signals (red arrow) from the
pathologic focus do not propagate along (are not collinear with) the axes of
any of standard ECG leads and therefore their magnitude does not reach
diagnostic thresholds to be properly detected. In such cases a correct
diagnosis is missed.
8/11/2019 Chapter 8 Cardiomyocytes
43/48
Signal Processing
The signal from the body is being amplified(the signals from the
body are small and weak, ranging from 0.5 mV to 5.0 mV),
filtered (to remove the noise), sampled (by sampling I mean it
goes to an Analog to Digital converter aka ADC) and then sent to
your computer through RS232 (wireless or any other way but
RS232 was chosen because it is the simplest and fastest to
make).
Data acquisition or where the signal of interest is represented by
a small voltage fluctuation superimposed on a voltage offset are
called instrumentation amplifiers. Instrumentation amplifiers have
a high CMRR(Common Mode Rejection Ratio) which means they
have the ability of a differential amplifier to not pass (reject) the
portion of the signal common to both the + and inputs.
The noise comes from muscle contractions, power lineinterference 50-60 Hz, electrode contact noise, noise from other
electronic devices and etc. The filter for the ECG application
should be a notch filter(high-pass and low-pass filter). It should
filter in the range from 0.5 Hz to 50 Hz.
A l d lt 12 l d ECG
8/11/2019 Chapter 8 Cardiomyocytes
44/48
A normal adult 12-lead ECG
8/11/2019 Chapter 8 Cardiomyocytes
45/48
Normal intracardiac recording
Normal intracardiac recording. Surface ECG leads I, II, and V1 are displayed with intracardiac ECGs from the high right
atrium (HRA), left atrium from the coronary sinus (CS), and AV junction to obtain a His bundle electrogram (HBE). T, time
lines; A, atrial activation; H, His bundle activation; V, ventricular activation. Atrial activation begins in the HRA and spreads
inferiorly to the low atrial septum, as recorded in the HBE, and the left atrium, as recorded in the CS. The AH and HV
intervals represent AV nodal and His-Purkinje conduction times, respectively. Vertical lines = 0.10 s.
Intracardiac electrograms. Schematic illustrations of several intracardiac electrograms contrasted with a conventional body-
surface electrocardiogram (ECG). HRA = high right atrial electrogram; HBE = His bundle electrogram, in which A = low
right atrial activity, H = His bundle activity, and V = ventricular septal activity; also shown are the P R, PA, AH, and HV
intervals.
8/11/2019 Chapter 8 Cardiomyocytes
46/48
Biventricular Pacing for Heart Failure- Cardiac resynchronization therapy (CRT)LVEF 35 MM, NYHC III or IV
Biventricular pacing for cardiac resynchronization
therapy.
-The right atrial and right ventricular pacing leads are
inserted in the usual manner.
-The left ventricular pacing lead is inserted via thecoronary sinus and advanced into a cardiac vein on the
lateral wall of the left ventricle.
-The location and accessibility of a suitable vein differ
from one patient to another, because of variability in the
coronary venous anatomy.
Summary: Cardiac Conduction System
8/11/2019 Chapter 8 Cardiomyocytes
47/48
y y
8/11/2019 Chapter 8 Cardiomyocytes
48/48
Sequence of Cardiac Conduction
Recommended