1. The cells of the heart
Two types of cardiac muscle cells that are involved in a normal heartbeat:
Specialized muscle cells of the conducting system
Contractile cells
The heart is an autonomic system that can work without neural stimuli – an intrinsic conduction system.
The autonomic function of the heart results from:
The pacemaker function – Autorhythmic cells
The conductive system that transfer those impulses throughout the heart

2. Properties of Cardiac Muscle
Aerobic muscle
No cell division after infancy - growth by hypertrophy
99% contractile cells (for pumping)
1% autorhythmic cells (set pace)

3. Electrical Conduction in Myocardial Cells
Membrane potential of autorhythmic cel
Membrane potential of contractile cell
Cells of SA node
Contractile cell
Intercalated disk with gap junctions
Depolarizations of autorhythmic cells rapidly spread to adjacent contractile cells through gap junctions.
Figure 14-17

4. Intrinsic cardiac conduction system – autorhythmic cells
Have unstable resting potentials/ pacemaker potentials
constantly depolarized slowly towards AP
At threshold, Ca2+ channels open
Ca2+ influx produces the rising phase of the action potential
Repolarization results from inactivation of Ca2+ channels and opening of voltage-gated K+ channels

5. Action potential Threshold Pacemaker potential 2 2 3 1 1 1 2 3
This slow depolarization is
due to both opening of Na+
channels and closing of K+
channels. Notice that the
membrane potential is
never a flat line. 1
Depolarization The
action potential begins when
the pacemaker potential
reaches threshold.
Depolarization is due to Ca2+
influx through Ca2+ channels. 2
Repolarization is due to
Ca2+ channels inactivating and
K+ channels opening. This
allows K+ efflux, which brings
the membrane potential back
to its most negative voltage. 3
Figure 18.13

6. Conduction System of Heart

7. Autorhythmic Cells Cardiac cells are linked by gap junctions
Location Firing Rate at Rest
SA node 70–80 APs/min*
AV node 40–60 APs/min
Bundle of His 20–40 APs/min
Purkinje fibers 20–40 APs/min
Cardiac cells are linked by gap junctions
Fastest depolarizing cells control other cells
Fastest cells = pacemaker = set rate for rest of heart
* action potentials per minute

8. Cardiac Electrical Connections

9. Cardiac contractile cells
Depolarization opens voltage-gated fast Na+ channels in the sarcolemma
Depolarization wave causes release Ca2+ that causes the cell contraction
Depolarization wave also opens slow Ca2+ channels in the sarcolemma
Ca2+ surge prolongs the depolarization phase (plateau)

10. Electrical Activity: Contractile Cell
Figure 13.13

11. 1 2 3 Action Depolarization is potential due to Na+ influx through
fast voltage-gated Na+
channels. A positive
feedback cycle rapidly
opens many Na+
channels, reversing the
membrane potential.
Channel inactivation ends
this phase. 1
Plateau 2
Tension
development
(contraction)
Membrane potential (mV) 1 3
Tension (g)
Plateau phase is
due to Ca2+ influx through
slow Ca2+ channels. This
keeps the cell depolarized
because few K+ channels
are open. 2
Absolute
refractory
period
Repolarization is
due to Ca2+ channels
inactivating and K+
channels opening. This
allows K+ efflux, which
brings the membrane
potential back to its
resting voltage. 3
Time (ms)
Figure 18.12

12. Action Potentials
Table 14-3

13. Conduction System of Heart

14. Electrical Conduction in the Heart1 1
SA node depolarizes.
SA node
AV node 2 2
Electrical activity goes rapidly to AV node via internodal pathways. 3
Depolarization spreads more slowly across atria. Conduction slows through AV node.
THE CONDUCTING SYSTEM OF THE HEART 4
Depolarization moves rapidly through ventricular conducting system to the apex of the heart.
SA node 3
Internodal pathways 5
Depolarization wave spreads upward from the apex.
AV node
AV bundle 4
Bundle branches
Purkinje fibers 5
Figure 14-18, steps 1–5

15. Cardiac Cycle
Cardiac cycle - The period between the start of one heartbeat and the beginning of the next.
refers to all events associated with blood flow through the heart
During the cycle, each of the four chambers goes through
Systole – contraction of heart muscle
Diastole – relaxation of heart muscle
An average heart beat (HR)/cardiac cycle is 75 bpm. That means that a cardiac cycle length is about 0.8 second.
Of that 0.1 second is the atrial contraction, 0.3 is the atrial relaxation and ventricular contraction.
The remaining 0.4 seconds are called the quiescent period which represent the ventricular relaxation

16. The sequence of events during a single heartbeat
Figure 18 Section 2 The Cardiac Cycle
Relaxation
Atria contract
Ventricles contract
Relaxation
Figure 18 Section 16

17. Phases of the Cardiac Cycle
Ventricular filling — takes place in mid-to-late diastole
AV valves are open
80% of blood passively flows into ventricles
Atrial systole occurs, delivering the remaining 20%
End diastolic volume (EDV): volume of blood in each ventricle at the end of ventricular diastole

18. Phases of the Cardiac Cycle
Ventricular systole
Atria relax and ventricles begin to contract
Rising ventricular pressure results in closing of AV valves
Isovolumetric contraction phase (all valves are closed)
In ejection phase, ventricular pressure exceeds pressure in the large arteries, forcing the SL valves open
End systolic volume (ESV): volume of blood remaining in each ventricle

19. Phases of the Cardiac Cycle
Isovolumetric relaxation occurs in early diastole
Ventricles relax
Backflow of blood in aorta and pulmonary trunk closes SL valves and causes dicrotic notch (brief rise in aortic pressure)

20. Phases of the Cardiac Cycle
Figure 20.16

21. Cardiodynamics
Movements and forces generated during cardiac contractions
End-diastolic volume (EDV) – the amount of blood in each ventricle at the end of ventricular diastole (before contraction begins)
End-systolic volume (ESV) - the amount of blood remains in each ventricle at the end of ventricular systole

22. Cardiodynamics Not all blood ejected Normal Adult 70 ml / beat
Stroke volume (SV) – The amount of blood that leaves the heart with each beat or ventricular contraction; EDV-ESV=SV
Not all blood ejected
Normal Adult 70 ml / beat
Ejection fraction – The percentage of end-diastole blood actually ejected with each beat or ventricular contraction.
Normal adult 55-70% (healthy heart)

23. Stroke Volume and Cardiac Output
Cardiac output (CO) – the amount of blood pumped by each ventricle in one minute.
Physiologically, CO is an indication of blood flow through peripheral tissues
Cardiac output equals heart rate times stroke volume; Normal CO: Approximately 4-8 liters/minute CO
Cardiac output
(ml/min) = HR
Heart rate
(beats/min) X SV
Stroke volume
(ml/beat)

24. The pressure changes within the aorta, left atrium, and left ventricle during the cardiac cycle
ATRIAL
DIASTOLE
ATRIAL
SYSTOLE
ATRIAL
SYSTOLE
ATRIAL DIASTOLE
VENTRICULAR
DIASTOLE
VENTRICULAR
SYSTOLE
VENTRICULAR DIASTOLE
120
Aortic valve closes.
Aortic valve
opens.
Aorta 90
Dicrotic notch
KEY
Atrial contraction begins.
Pressure (mm Hg)
Atria eject blood into ventricles. 60
Atrial systole ends; AV valves close.
Left
ventricle
Isovolumetric contraction.
Ventricular ejection occurs.
Semilunar valves close. 30
Isovolumetric relaxation occurs.
Left atrium
Left AV
valve closes.
Left AV valve opens.
AV valves open; passive ventricular
filling occurs.
Figure The cardiac cycle creates pressure gradients that maintain blood flow
100
200
300
400
500
600
700
800
Time (msec)
The correspondence of the heart sounds with events during the cardiac cycle S1 S2 S4 S3 S4
Heart sounds
“Lubb”
“Dubb”
Figure 24

25. (mid-to-late diastole)
Left heart
QRS P T P
Electrocardiogram
Heart sounds
1st
2nd
Dicrotic notch
Aorta
Pressure (mm Hg)
Left ventricle
Atrial systole
Left atrium
EDV
Ventricular
volume (ml) SV
ESV
Atrioventricular valves
Open
Closed
Open
Aortic and pulmonary valves
Closed
Open
Closed
Phase 1 2a 2b 3 1
Left atrium
Right atrium
Left ventricle
Right ventricle
Ventricular
filling
Atrial
contraction
Isovolumetric
contraction phase
Ventricular
ejection phase
Isovolumetric
relaxation
Ventricular
filling 1 2a 2b 3
Ventricular filling
(mid-to-late diastole)
Ventricular systole
(atria in diastole)
Early diastole
Figure 18.20

26. Factors Affecting Cardiac Output
Figure 20.20

27. Extrinsic Innervation of the Heart
Heartbeat is modified by the ANS
Cardiac centers are located in the medulla oblongata
Cardioacceleratory center innervates SA and AV nodes, heart muscle, and coronary arteries through sympathetic neurons
Cardioinhibitory center inhibits SA and AV nodes through parasympathetic fibers in the vagus nerves

28. Autonomic Inputs to Heart

29. Effect inotropy – (from Greek, meaning fiber) effect on contractility of the heart
Effect chronotropy – effect on HR
Effect dromotropy – Derives from the Greek word "Dromos", meaning running.
A dromotropic agent is one which affects the conduction speed in the AV node
Sympathetic stimuli has a positive effect (increase) all
Parasympathetic stimuli has a negative effect (decrease) all

30. Autonomic Nervous System Regulation
In healthy conditions, parasympathetic effects dominate and slows the rate of the pacemaker from bpm to a bpm.
The binding of Ach to muscarinic receptors (M2) inhibit NE release (mechanism by which vagal stimulation override sympathetic stimulation)
Sympathetic nervous system is activated by emotional or physical stressors
Norepinephrine causes the pacemaker to fire more rapidly (and at the same time increases contractility)
Parasympathetic nervous system opposes sympathetic effects
Acetylcholine hyperpolarizes pacemaker cells by opening K+ channels
The heart at rest exhibits vagal tone (parasympathetic)

31. Autonomic Neurotransmitters Alter Heart Rate
KEY
Integrating center
Cardiovascular control center in medulla oblongata
Efferent path
Effector
Tissue response
Sympathetic neurons (NE)
Parasympathetic neurons (Ach)
1-receptors of autorhythmic cells
Muscarinic receptors of autorhythmic cells
Na+ and Ca2+ influx
K+ efflux; Ca2+ influx
Hyperpolarizes cell and rate of depolarization
Rate of depolarization
Heart rate
Heart rate
Figure 14-27

32. Heart rate under three conditions: at rest, under parasympathetic
stimulation, and under sympathetic stimulation
A prepotential or pacemaker potential
in a heart at rest
Normal (resting)
Prepotential
(spontaneous
depolarization)
+20
Membrane
potential
(mV)
–30
Figure The intrinsic heart rate can be altered by autonomic activity
Threshold
–60
Heart rate: 75 bpm
0.8
1.6
2.4
Time (sec)
Figure 32

33. Parasympathetic stimulation
Heart rate under three conditions: at rest, under parasympathetic
stimulation, and under sympathetic stimulation
A prepotential or pacemaker potential
in a heart at rest
Increased heart rate resulting when
ACh released by parasympathetic
neurons opens chemically gated K+
channels, thereby slowing the rate
of spontaneous depolarization
Parasympathetic stimulation
+20
Membrane
potential
(mV)
–30
Figure The intrinsic heart rate can be altered by autonomic activity
Threshold
Hyperpolarization
–60
Heart rate: 40 bpm
Slower depolarization
0.8
1.6
2.4
Time (sec)
Figure 33

34. Sympathetic stimulation
Heart rate under three conditions: at rest, under parasympathetic
stimulation, and under sympathetic stimulation
Decreased heart rate resulting when
NE released by sympathetic neurons
leads to the opening of ion channels,
increases the rate of depolarization
and shortens the period of
repolarization
Sympathetic stimulation
+20
Membrane
potential
(mV)
–30
Figure The intrinsic heart rate can be altered by autonomic activity
Threshold
Reduced repolarization
–60
More rapid
depolarization
Heart rate: 120 bpm
0.8
1.6
2.4
Time (sec)
Figure 34

35. Chemical Regulation of Heart Rate
Hormones
Epinephrine from adrenal medulla enhances heart rate and contractility
Thyroxine increases heart rate and enhances the effects of norepinephrine and epinephrine
Intra- and extracellular ion concentrations (e.g., Ca2+ and K+) must be maintained for normal heart function

36. Homeostatic Imbalances
Tachycardia: abnormally fast heart rate (>100 bpm)
If persistent, may lead to fibrillation
Bradycardia: heart rate slower than 60 bpm
May result in grossly inadequate blood circulation
May be desirable result of endurance training

37. Factors Affecting Stroke Volume
Figure 20.23

38. Regulation of Stroke Volume
SV = EDV – ESV
Three main factors affect SV
Preload
Contractility
Afterload

39. Regulation of Stroke Volume
Preload
The amount of tension on a muscle before it begins to contract. The preload of the heart is determined by the EDV.
In general, the greater the EDV the larger is the stroke volume : EDV-ESV=SV
These relationships is known as the Frank-Starling principle/Sterling’s law of the heart :
The force of cardiac muscle contraction is proportional to its initial length
The greater the EDV the larger the preload

40. Preload and Stroke Volume
Frank-Starling law states
Stroke volume increase as EDV increases
EDV is affected by venous return
Venous return is affected by
Skeletal muscle pump
Respiratory pump
Sympathetic innervation

41. Factors Affecting stroke volume - Preload/EDV
Stroke volume is the difference between the EDV and ESV. Changes in either one can change the stroke volume and cardiac output:
The EDV volume is affected by 2 factors:
The filling time – duration of ventricular diastole; depends on HR – the faster the HR the shorter is the available filing time
The venous return – changes in response to several changes: cardiac output, blood volume, peripheral circulation.

42. Reminder - Length-tension relationship
The force of muscle contraction depends on the length of the sarcomeres before the contraction begins
On the molecular level, the length reflects the overlapping between thin and thick filaments
The tension a muscle fiber can generate is directly proportional to the number of crossbridges formed between the filament

43.  Preload =  Contractility (to a point)

44. Stroke Volume
Length-force relationships in intact heart: a Starling curve
Figure 14-28

45. EDV increase (preload increased)
Diastolic filling increased
EDV increase (preload increased)
Cardiac muscle stretch increased
Force of contraction increased
Ejection volume increased

46. Regulation of Stroke Volume - Afterload
The amount of resistance the ventricular wall must overcome to eject blood during systole (influenced by arterial pressure).
The greater is the afterload, the longer is the period of isovolumetric contraction (ventricles are contracting but there is no blood flow), the shorter the duration of ventricular ejection and the larger the ESV – afterload increase – stroke volume decrease
Hypertension increases afterload, resulting in increased ESV and reduced SV

47. Regulation of Stroke Volume - Contractility
Force of ventricular contraction (systole) regardless of EDV
Positive inotropic agents increase contractility
Increased Ca2+ influx due to sympathetic stimulation
Hormones (thyroxine and epinephrine)
Negative inotropic agents decrease contractility
Increased extracellular K+ (hyperpolarization)
Calcium channel blockers (decrease calcium influx)

48. Congestive Heart Failure (CHF)
Progressive condition where the CO is so low that blood circulation is inadequate to meet tissue needs
Caused by
Coronary atherosclerosis
Persistent high blood pressure
Multiple myocardial infarcts (decreased blood supply and myocardial cell death)
Dilated cardiomyopathy (DCM) – heart wall weakens and can not contract efficiently. Causes are unknown but sometimes associated with toxins (ex. Chemotherapy), viral infections, tachycardia and more

49. Electrocardiography (ECG or EKG)
Body fluids are good conductors which allows the record of the myocardial action potential extracellularly
EKG pairs of electrodes (leads) one serve as positive side of the lead and one as the negative
Potentials (voltage) are being measured between the 2 electrodes
EKG is the summed electrical potentials generated by all cells of the heart and gives electrical “view” of 3D object (different from one action potential)
EKG shows depolarization and repolarization

50. Einthoven’s Triangle Right arm Left arm I
Electrodes are attached to the skin surface. II
III
A lead consists of two electrodes, one positive and one negative.
Left leg
Figure 14-19

51. The Electrocardiogram
Three major waves: P wave, QRS complex, and T wave
Figure 14-20

52. Electrical Activity of Heart
P wave: atrial depolarization
QRS complex: ventricular depolarization and atrial repolarization
T wave: ventricular repolarization
PQ segment: AV nodal delay
QT segment: ventricular systole
QT interval: ventricular diastole

53. Electrical Activity of Heart – normal values
Figure 13.16

54. Correlation between an ECG and electrical events in the heart

55. Electrical Activity Figure 14-21 (1 of 9)
P wave: atrial depolarization
START P
ELECTRICAL
EVENTS OF THE CARDIAC
CYCLE
Figure (1 of 9)

56. Electrical Activity Figure 14-21 (9 of 9)
P wave: atrial depolarization
START P
The end R
PQ or PR segment: conduction through AV node and AV bundle P T Q S P
Atria contract
T wave: ventricular repolarization
Repolarization
ELECTRICAL
EVENTS OF THE CARDIAC
CYCLE R P T Q S
Q wave P
ST segment Q R P
R wave R Q S
Ventricles contract R P Q P
S wave Q S
Figure (9 of 9)

57. Homeostatic Imbalances
Defects in the intrinsic conduction system may result in
Arrhythmias: irregular heart rhythms
Uncoordinated atrial and ventricular contractions (heart block)
Fibrillation: rapid, irregular contractions; useless for pumping blood

58. Important examples of cardiac arrhythmias
Premature Atrial Contractions (PACs)
Premature atrial contractions (PACs) often occur in healthy individuals. In a
PAC, the normal atrial rhythm is momentarily interrupted by a “surprise” atrial
contraction. Stress, caffeine, and various drugs may increase the incidence of
PACs, presumably by increasing the permeabilities of the SA pacemakers. The
impulse spreads along the conduction pathway, and a normal ventricular
contraction follows the atrial beat. P P P
Paroxysmal Atrial Tachycardia (PAT)
In paroxysmal (par-ok-SIZ-mal) atrial tachycardia, or PAT, a premature atrial
contraction triggers a flurry of atrial activity. The ventricles are still able to keep
pace, and the heart rate jumps to about 180 beats per minute. P P P P P P
Atrial Fibrillation (AF)
Figure Normal and abnormal cardiac activity can be detected in an electrocardiogram
During atrial fibrillation (fib-ri-LĀ-shun), the impulses move over the atrial
surface at rates of perhaps 500 beats per minute. The atrial wall quivers instead
of producing an organized contraction. The ventricular rate cannot follow the
atrial rate and may remain within normal limits. Even though the atria are now
nonfunctional, their contribution to ventricular end-diastolic volume is so small
that the condition may go unnoticed in older individuals.
Figure 58

59. Important examples of cardiac arrhythmias
Premature Ventricular Contractions (PVCs)
Premature ventricular contractions (PVCs) occur when a Purkinje cell or
ventricular myocardial cell depolarizes to threshold and triggers a premature
contraction. Single PVCs are common and not dangerous. The cell responsible
is called an ectopic pacemaker. The frequency of PVCs can be increased by
exposure to epinephrine, to other stimulatory drugs, or to ionic changes that
depolarize cardiac muscle cell membranes. P T P T P T
Ventricular Tachycardia (VT)
Ventricular tachycardia is defined as four or more PVCs without intervening
normal beats. It is also known as VT or V-tach. Multiple PVCs and VT may
indicate that serious cardiac problems exist. P
Ventricular Fibrillation (VF)
Figure Normal and abnormal cardiac activity can be detected in an electrocardiogram
Ventricular fibrillation (VF) is responsible for the condition known as cardiac
arrest. VF is rapidly fatal, because the ventricles quiver and stop pumping blood.
Figure 59

60. ECG Arrhythmias: Fibrillation
Ventricular Fibrillation
Loss of coordination of electrical activity of heart
Death can ensue within minutes unless corrected
Figure (4 of 4)

61. Homeostatic Imbalances
Defective SA node may result in
Ectopic focus: abnormal pacemaker takes over
If AV node takes over, there will be a junctional rhythm (40–60 bpm)
Defective AV node may result in
Partial or total heart block
Few or no impulses from SA node reach the ventricles

62. First and second degree Heart Block
Slowed/diminished conduction through AV node occurs in varying degrees
First degree block
Increases duration PQ segment
Increases delay between atrial and ventricular contraction
Second degree block
Lose 1-to-1 relationship between P wave and QRS complex
Lose 1-to-1 relationship between atrial and ventricular contraction

63. Third Degree Heart Block
Third degree block
Loss of conduction through the AV node
P wave becomes independent of QRS
Atrial and ventricular contractions are independent