Cardiac Muscle

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Cardiac Muscle
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Figure 1.02. The cardiac cycle in terms of time
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Figure 1.02B. Left heart pressures during one
cardiac cycle
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Figure 1.02C. Ventricular blood volume during one
cardiac cycle
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Figure 1.02D. Aortic blood flow during one
complete cardiac cycle
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Figure 1.02E. ECG and heart sounds during one
cardiac cycle
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Figure 1.02F. Right heart pressures during one
cardiac cycle
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Figure 1.05. Normal blood pressure and oxygen
saturation values
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Length-tension curves (diagrams) for skeletal and
cardiac muscle
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Figure 12M0. The effect of norepinephrine in
augmenting tension and rate of tension
development (Inotropicity) produced during
isometric muscle twitches
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Figure 14. Bowditch effect (ie., Treppe,
Staircase, force frequency relationship)
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Refractory Period

• Long, compared to skeletal muscle
• Prevents tetanus, guarantees a period of filling
• Prevents ineffective tachycardia
• Prevents re-entry ("circus" movement)

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Two Kinds of Myocardial Cells

• Pacemaker - exhibit automaticity (rising phase 4
  prepotential)
• primary - SA nodal
• reserve - SA nodal, purkinje, AV nodal
• Follower - no automaticity
• (stable phase 4 potential atrium, ventricle)

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Figure 3. The various ion pumps of the cell.
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Figure 2M0. The three slow Ca channel states
resting, active, inactive."d" and "f" are upper
and lower gates in the channel.
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Ion Channels

• Fast - initial rapid inward Na current. -
  secondary outward K movement repolarization
• Slow - Ca moves inward, responsible for
  maintained depolarization of the "plateau phase"
  (Phase 2)
• An increase in contraction frequency increases
  Ca movement inward, giving the "staircase"
  phenomenon (Treppe, Bowditch) in cardiac muscle.

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Figure 4M0. The fast sodium and slow calcium
channels. The fast channel is in its "resting"
modethe slow channel is in its depolarization
mode, ie. active state (Ca ions moving
through). The black dot indicates Nifedipine
attachment site.TTX Tetrodotoxin, Nifedipine
a medically-used Ca channel blocker."m" and
"h" are upper and lower gates in the Na
channel."d" and "f" are upper and lower gates in
the Ca channel.
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Figure 5M0. Changes in transmembrane potential
before and during depolarization in various types
of myocardial cells.Not all the depolarization /
repolarizations look like that in Figure 1.
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Mechanisms for Changing Pacemaker Cell
Automaticity

• Hyperpolarize/hypopolarize overdrive suppression
• Alteration of slope (rate of rise) of
  pre-potential (diastolic potential)
• Alteration of threshold e.g. epinephrine
  increases gCa (hypopolarizes), acetylcholine
  increases gK (hyperpolarizes)

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Factors Determining Action Potential Conduction
Velocity

• Amplitude rate of change of action potential -
  increasing velocity, decreasing time
• - if large, more likely to depolarize adjacent
  cells
• Anatomy of conducting cells - increased diameter,
  increases conduction velocity
• - number of interconnections
• - longer nexus junctions (Purkinje cells)
• "Cable Properties" of the conducting system

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Factors Affecting Conduction Through the AV
Junction

• Speeds -
• Catecholamines
• Atropine - blocks Acetylcholine
• Quinidine - inhibits vagal effects
• Slows Acetylcholine
• Digitalis - central vagal (parasympathetic)
  stimulation
• Inhibitors of acetylcholine esterase, Ca
  antagonists (e.g. verapamil)
• An increased number of impulses arriving at AV
  junction increases refractoriness

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Various Conditions of Muscle Contraction

• Isotonic
• Unloaded
• Preloaded
• Afterloaded (to less than isometric)
• Isometric

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Comparing isotonic and isometric muscle
contractions.

• indicates it occurs - does not occur

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Figure 6M0. Isometric and isotonic skeletal
muscle twitches following a single action
potential
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Figure 9M0. Isometric twitch tension as it is
influenced by preload (ie. initial length,
Frank-Starling mechanism)
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Figure 10M0. Velocity of muscle shortening and
power output as each is influenced by increasing
afterload
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Figure 8M0. Velocity of shortening (isotonic
contraction) as it is altered by afterload and
preload
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Effects of Increased Preload on Velocity of
Shortening, etc

• Increased velocity of shortening (isotonic) at
  any given afterload
• Unaltered Vmax at zero afterload
• Increased muscle length
• Increased tension development (isometric)

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Effects of Afterload on Velocity of Shortening

• Maximum at no load
• Zero at maximum load (isometric)
• Intermediate with some, not maximum load

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Effects of Increased Inotropicity on Velocity of
Shortening, etc.

• Increased velocity of shortening (isotonic) at
  any given afterload
• Increased Vmax at zero afterload
• Same muscle length
• Increased tension development (isometric), and
  increased rate of contraction and relaxation

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Figure 13M0. Velocity of muscle shortening
and the influence of a catecholamine such as
norepinephrine (Inotropicity) in modifying the
relationship
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Figure 7M0. Mechanisms for altering isometric
tension in cardiac muscle vs skeletal muscle
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Factors Affecting Heart Rate

• Leading to an INCREASE
• decreased activity of baroreceptors in the
  arteries, LV, and pulm. circ. (1)
• inspiration (2)
• excitement, anger, most painful stimuli (1)
• hypoxia (1?)
• exercise (1)
• norepinephrine (1) , epinephrine
• thyroid hormones
• fever
• Bainbridge reflex Leading to a DECREASE
• increased activity of baroreceptors in the
  arteries, LV, and pulm. circ. (2)
• expiration (1)
• fear, grief (2)
• stimulation of pain fibers in trigeminal nerve
• increased intracranial pressure (Cushing Reflex)
  (1)

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Actions of Vagal Parasympathetic Neurons to the
Heart (through release of acetylcholine)

• ...... Site ................................
  Action ..........................................
  Affecting ......
• sino-atrial node ................... decreases
  heart rate ........... chronotropicity
• atrio-ventricular node ............ slowed AV
  conduction ..... chronotropicity
• atrio-ventricular node .. delayed conduction /
  increased refractoriness ..
  chronotropicity
• Note There are few/no parasympathetic nerve
  endings on the ventricular myocardium, so while
  acetylcholine is a potential negative inotrope
  for the ventricles, it is not released there.

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Figure 2.01. Schematic of vagal escape.
Acetylcholine release from parasympathetic ends
on the SA nodeand AV node Junctional tissue
increases refractoriness and depresses conduction
velocity.Intense stimulation will stop
ventricular depolarization, ie. contraction.
Reserve pacemakers come into play.
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Control of Cardiac Performance STROKE VOLUME

• Extrinsic
• Release of the following substances from the
  sympathetic and parasympathetic sympathetic
  branches of the autonomic nervous system, affect
  inotropicity
• norepinephrine () - neural
• acetylcholine (-) - neural
• epinephrine () - blood borne These actions are
  mediated through cardiopulmonary receptors, such
  as the carotid sinus (aortic) baroreceptors,
  carotid (aortic) body chemoreceptors, central
  chemo-receptors, venae cavae/atrial volume
  receptors (Bainbridge), and the ventricular
  volume receptors.
• Attention Inotropicity (ie. contractility) and
  strength of contraction are not synonomous.
  Increased / decreased strength of contraction can
  be achieved by changing preload(ie.
  Frank-Starling) with no change in inotropicity.
  Inotropicity reflects the biochemical state
  within the muscle (eg. CaltSUPlt supgt, ATP), not
  simply the positioning of the thick and thin
• myofilaments as determined by stretch.
  Intrinsic
• Frank-Starling - through preload (heterometric
  autoregulation)
• afterload - through increased / decreased
  arterial blood pressure acting on aortic valve.
• Anrep effect - laboratory curiousity?
• Bowditch effect (homeometric autoregulation)
  (Treppe, Staircase)
• environment - ischemia, O2, CO2
• cardiac hypertrophy - longterm effect In
  actual fact, there are few parasympathetic fibers
  in the ventricular myocardium, so ACH has little
  practical effect physiologically on ventricular
  inotropicity (contractility).

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Figure 2.02. Frank-Starling (or ventricular
function) curve. See cardiac muscle
length-tension curve.The black curve defines a
single inotropic state.
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Major Factors Determining Myocardial Stretch

• Total blood volume
• Body position relative to the earth and gravity
  pull
• Intrathoracic pressure
• Intrapericardial pressure
• Venous tone
• Pumping action of the skeletal muscle
• Atrial contribution to ventricular filling

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Figure 2.03. Some factors contributing to
afterload. What are shown here are the effects of
increased vascular resistance and vascular
compliance. Another major factor not shown is
heart dimension, ie. a dilated heart sustains
greater afterload at the same arterial or
ventricular pressure than a smaller heart (a
larger heart has larger radii of curvature and
through the Law of Laplace is at greater
mechanical disadvantage relative to internal
pressure than a smaller heart).
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Major factors determining myocardial contractile
state (ie. inotropicity)

• Sympathetic nerve impulses (normal)
• Circulating catecholamines (normal)
• Force-frequency relation (Bowditch, Treppe,
  Staircase) Normal)
• Various natural inotropic agents (normal)
• Digitalis, other non-natural inotropic agents
  (medical)
• Anoxia, hypercapnia, acidosis (pathologic)
• Pharmacologic depressants (medical / pathologic)
• Loss of myocardium (pathologic)
• Intrinsic depressants (normal / pathologic)
• Attention Inotropicity (ie. contractility) and
  strength of contraction are not synonomous.
  Increased / decreased strength of contraction can
  be achieved by changing preload(ie.
  Frank-Starling) with no change in inotropicity.
  Inotropicity reflects the biochemical state
  within the muscle (eg. CaltSUPlt supgt, ATP), not
  simply the positioning of the thick and thin
• myofilaments as determined by stretch.

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Figure 2.04. Two Frank-Starling curves
demonstrating altered inotropicity Blue - lower
inotropicity Green - higher inotropicity.
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Inotropic agents

• Positive
• Catecholamines (epinephrine, norepinephrine,
  isoproterenol)
• Ca
• Cardiac glycosides (digitalis) Negative
• Ischemia/hypoxia
• Acetylcholine
• Heart Failure

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Stages of the cardiac cycle
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The cardiac cycle as a loop, independent of time
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Figure 2.05. Changing pump conditions A,
changing preload B, changing afterload C,
changing contractile state Note Review
loop-display.
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changing afterload, preload remains constant
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Alterations in contractile state using systolic
reserve volume (more complete emptying), through
enhanced inotropicity
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Figure 2.07. Major factors contributing to
cardiac output - Summary
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Figure 2.06. Mechanisms of cardiac hypertrophy.
Concentric and Eccentric Hypertrophy
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Changes in Gene Expression in Cardiac Overload

• Quantitative changes
• Coordinated increase in protein (myosin, actin,
  myoglobin, Ca channels, mitochondria, surface
  membrane) and RNA (m, r and t) synthesis.
• Regulated at a transcriptional and at the
  translational level.
• Adaptational, because it multiplies contractile
  units and decreases wall stress. Qualitative
  changes
• Several shifts in isoforms (myosin, creatine
  kinase, actin, tropomyosin, LDH, Na-K, ATPase,
  and SR protein).
• Due to an isogene change in expression (myosin).
• Adaptational because it decreases Vmax. and
  improves heat production.

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Figure 10. Velocity of muscle shortening and
power output as each is influenced by increasing
afterload
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Ejection Fraction

• EF (EDV - ESV) / EDV
• or
• EF SV / EDV, e.g. EF 100 ml / 150 ml 0.66
• Note SV EDV - ESV

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Figure 2.09. Assessment of ventricular
performance. PEP, LVET, and the ratio of PEP /
LVET.
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Figure 2.08. Factors affecting pre-ejection period
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Figure 2.10. Range of ejection fractions. The
normal range may extend to 0.82 or 0.84.Values
below 0.15 are usually incompatible with life.
Note The heart wall may be said to display
normal kinesis, hypokinesis, hyperkinesis,
akinesis (no motion), dyskinesis (paradoxical
wall motion).
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Figure 3.01. Blood flow distribution and
arteriovenous oxygen differences. The term
"oxygen content" actually means "oxygen
concentration".Arterial O2 concentration is
constant, while venous O2 concentration varies
from organ to organ, tissue to tissue
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Ischemia

• Increased A-V O2 diff. at rest usually indicates
  ischemia. Ischemia is relieved by
• increasing blood flow
• decreasing O2 consumption Increased A-V lactate
  indicates inadequate flow heart usually uses
  lactate, in ischemia it produces lactate

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The concept of Cardiac Reserve
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Figure 3.02. The concept of cardiovascular
reserve. Cardiac Output is in units of liters
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Fick Equation

• Cardiac output (L/min.) O2 uptake (ml O2/min.)
  / A-V O2 diff. (ml O2/L blood)
• For Example C.O. 250/ (0.19 - 0.14) 5100
  ml/min.
• O2 uptake 250 ml/min. Arterial O2 content
  0.19 ml/ml Venous O2 content 0.14 ml/ml

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Figure 3.03. A dye-dilution curve
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Figure 3.04. Effects of different levels of
exercise (work) on cardiovascular function
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Figure 3.05. Redistribution of cardiac output
with increased exercise / workload
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Figure 3.06. Specific blood flow in various
organs and tissues
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Figure 3.07. The coronary vessels
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Figure 3.11. An angiogram of normal coronary
vessels in an opened heart preparation (vessels
filled with radiopaque material). On right is the
horizontal main right coronary artery with small
dscending twigs. On the left is the major left
descending ramus and the horizontal major left
circumflex ramus. Between these two are several
large diagonal branches. The vessels show
progressively diminishing lumina with no
irregular narrowings or obstructions.
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Thallium StudyExamine the images below obtained
during exercise stress and at rest for a normal
patient. Note the uniform distribution in the
walls of both right and left ventricle
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Figure 1. The conduction system for the cardiac
action potential. Normally the SA node
depolarizes first and then the rest of the atria.
After a delay at the AV junctional tissue, the
action potential is conducted down the AV node,
to the AV bundle, to the bundle branches, to the
Purkinje fibers, and then to the right and left
ventricles.
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Figure 1M0. Electrophysiologic changes during
the cardiac cycle, including threshold current,
transmembrane potential and ion conductances over
time. The circled numbers identify the five
phases of the process.
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The 5 Phases of Myocardial Cell Electrophysiology
(follower cells only)

• Phase 4 -Polarized Cell (-) inside, ()
  outside due mainly to Na K ion positioning
  and higher permeability of membrane to K,
  allowing loss of intracellular () charge.
• Phase 0 -Cell Depolarization greatly increased
  membrane permeabilty to Na ions, which rush in
  through fast channels, down conc. gradient,
  reversing cell polarity (fast current).
• Phase 1 -Partial Repolarization loss of Na
  conductance, transient influx of Cl- ions and
  outflow K ions.
• Phase 2 -Plateau due to the slow inward flow of
  Ca ions through slow channels (i.e. increased
  Ca conductance) (also some inward movement of
  Na through slow channels and outward movement of
  K). Phase 2 includes most of the absolute
  refractory period.
• Phase 3 -Rapid Repolarization decreased Ca
  conductance and increased K conductance, thus K
  moves out inside of cell again becomes (-)
  relative to outside Na/K pump re-establishes
  distribution of ions. Supranormal excitabilty
  present early in phase 3, thus greatest chance of
  ectopic beat.

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Table 6. HIERARCHY OF PACEMAKERS BASED ON
INTRINSIC FIRING RATES

• __________________________________________________
  _____
• Sinoatrial Node .............................. 70
  per min.
• Atrioventricular Node .................. 60 per
  min.
• Ventricle .......................................
  30-40 per min. ___________________________________
  ____________________

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Figure 7. Sequence of depolarization /
repolarization of the heart.
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Figure 2. Sequence of cardiac excitation and
associated changes in the ECG.
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Figure 3. The Einthoven Triangle, showing Leads
I, II and III.
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Figure 4. A moving dipole and how it is "sensed"
in front, behind and at oblique angles
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Figure 11. Configuration of the standard limb
leads, situated in the frontal (coronal) plane.

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Figure 12. Configuration of the augmented
limb leads, situated in the frontal (coronal)
plane.
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Figure 13. Configuration of the precordial
(chest) leads, situated in the transverse
(horizontal) plane.
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Figure 5. Standard terminology for the ECG
(Lead aVf, 75 beats/min.).
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Figures 9. Method for accurately determining mean
electrical axis of the heart (ventricles) - Step
1.
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Figures 10. Method for accurately determining
mean electrical axis of the heart (ventricles) -
Step 2. Go to Step 1
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Figure 8. Electrocardiograms of two individuals,
one sedentary and one an endurance athlete
(Standard paper speed 25 mm/sec., large
horizontal squares 200 msec., small squares 40
msec.)
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Figure 6. Comparison of the ECG's of an
office worker and an athlete. (Standard paper
speed 25 mm/sec., large horizontal squares 200
msec., small squares 40 msec.)
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Figure 14. Normal sinus rhythm. Impulses
originate at the SA node at the normal rate. All
complexes are evenly spaced rate 60 - 100/min.
PR interval 120 - 200 msec
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Figure 15. Sinus bradycardia. Impulses
originate at the SA node at a slow rate. All
complexes are normal, evenly spaced rate
lt60/min. PR interval 120 - 200 msec.
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Figure 16. First degree AV block. Fixed but
prolonged PR interval. P wave precedes each QRS
complex but PR interval, although uniform, is
gt0.2 sec. (gt5 small boxes).
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Figure 17. Second-degree heart block Mobitz I or
Wenchebach. Progressive lengthening of the PR
interval with intermittent dropped beats.
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Figure 21. Third-degree (complete) heart (AV)
block. There is no relationship between P waves
and QRS complexes QRS rate is slower than P wave
rate. Impulses originate at both the SA node (P
waves) and below the site of block in the AV node
(junctional rhythm) conducting to the ventricles.
Atria and ventricles depolarize independently,
QRS complexes are less frequent regular at 20 to
40/min but normal in shape
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Figure 22. Third-degree (complete) heart (AV)
block. There is no relationship between P waves
and QRS complexes QRS rate is slower than P wave
rate. Impulses originate at SA node (P waves) and
also below the site of block in ventricles
(idioventricular rhythm). Atria and ventricles
depolarize independently, QRS complexes are less
frequent regular at 20 to 40/min but wide and
abnormal in shape.
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Figure 18. Junctional rhythm. Impulses originate
in the AV node or AV junctional tissue, with
retrograde and antegrade transmission. In this
example, retrograde transmission is taking place
into the atria, giving an inverted P wave. The
ventricular rate is slower than with sinus rhythm
and the QRS is narrow. If there is also sinus
node depolarization, a normal-appearing P wave
may be present. If a wandering pacemaker is
present in the atria, inverted P waves can
precede the QRS complex
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Figure 19. Idioventricular rhythm. No P waves
(ventricular impulse origin). Rate lt40 / min.
QRS gt 0.10 sec.
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Figure 20. Intraventricular conduction defect
(IVCD), including right or left bundle branch
block. Wide QRS (2-1/2 small boxes), often
notched, preceded by P wave with normal PR
interval.
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Figure 23. Wandering atrial pacemaker. Impulses
originate from varying points in atria. Variation
in wave contour, PR interval, PP and thus RR
intervals.
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Figure 24. Atrial flutter. Impulses travel in
circular course in atria, setting up regular,
rapid (220 to 300/min.) flutter (F) waves without
any isoelectric baseline. Ventricular rate (QRS)
is regular or irregular and slower depending upon
the degree of block.
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Figure 25. Atrial fibrillation - impulses take
random, chaotic pathways in atria. Baseline
coarsely or finely irregular P waves absent.
Ventricular response (QRS) irregular, slow or
rapid
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Figure 26. Ventricular tachycardia. Arrow
shows slowed conduction in the margin of the
ischemic area, which permits a circular course of
impulses and re-entry with rapid repetitive
depolarization.
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Figure 27. Ventricular fibrillation.
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Figure 28. The effect of increases in serum K
concentration on the ECG
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• the end