1. The Cardiovascular System: The Heart: Part B18
The Cardiovascular System: The Heart: Part B

2. Heart Valves
Heart valves ensure unidirectional blood flow through the heart (prevent backflow)
Atrioventricular (AV) valves lie between the atria and the ventricles
AV valves prevent backflow into the atria when ventricles contract
Chordae tendineae anchor AV valves to papillary muscles
Semilunar valves prevent backflow of blood into the ventricles
Aortic semilunar valve lies between the left ventricle and the aorta
Pulmonary semilunar valve lies between the right ventricle and pulmonary trunk

3. The conductive system
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
Two types of cardiac muscle cells that are involved in a normal heartbeat:
Specialized muscle cells of the conducting system
Contractile cells

4. Cardiac Muscle Contraction
Depolarization opens voltage-gated fast Na+ channels in the sarcolemma
Reversal of membrane potential from –90 mV to +30 mV
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)

5. Contractile Cells
In skeletal muscle and neurons, an action potential falls back to Resting Membrane Potential (RMP) within 1-2 msec, but in cardiac muscle, slow calcium channels remain open longer (after sodium channels close), prolonging the depolarization of the cell.
As long as the action potential is in its plateau and calcium is entering the myocytes, the myocytes contract.
These plateaus are more pronounced in the ventricles.
Cardiac muscle has an absolute refractory period of 250 msec, compared with 1–2 msec in skeletal muscle.
The cardiac muscle must return completely to resting potential before it can be contracted again.
As a result, the heart can not go through tetanus contraction.

6. Action potential in contractile cardiac muscle cells

7. Heart Physiology: Electrical Events
Intrinsic cardiac conduction system
A network of noncontractile (autorhythmic) cells that initiate and distribute impulses to coordinate the depolarization and contraction of the heart
Have unstable resting potentials/ pacemaker potentials (they constantly depolarized slowly towards AP – hyperpolarization closes K+ and opens Na+)
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

8. Heart Physiology: Sequence of Excitation
Sinoatrial (SA) node (pacemaker)
Generates impulses about 75 times/minute (sinus rhythm)
Depolarizes faster than any other part of the myocardium
Atrioventricular (AV) node
Smaller diameter fibers; fewer gap junctions
Delays impulses approximately 0.1 second
Depolarizes 50 times per minute in absence of SA node input

9. Heart Physiology: Sequence of Excitation
Atrioventricular (AV) bundle (bundle of His)
Only electrical connection between the atria and ventricles
Right and left bundle branches
Two pathways in the interventricular septum that carry the impulses toward the apex of the heart
Purkinje fibers
Complete the pathway into the apex and ventricular walls
AV bundle and Purkinje fibers depolarize only 30 times per minute in absence of AV node input

10. The upper part of the heart (the 2 atria) is insulated from the lower part
Electrical excitation can pass from the atria to the ventricles only at the AV node

11. 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

12. 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

13. Electrocardiography EKG is made of waves and segments
Waves are deflections above or below baseline
Three waves
P wave: depolarization of SA node
QRS complex: ventricular depolarization (Atrial repolarization record is masked by the larger QRS complex)
T wave: ventricular repolarization
Segments are sections of baseline between waves

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

15. 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

16. (a) Normal sinus rhythm. (b) Junctional rhythm. The SA
node is nonfunctional, P waves
are absent, and heart is paced by
the AV node at beats/min.
(c) Second-degree heart block.
Some P waves are not conducted
through the AV node; hence more
P than QRS waves are seen. In
this tracing, the ratio of P waves
to QRS waves is mostly 2:1.
(d) Ventricular fibrillation. These
chaotic, grossly irregular ECG
deflections are seen in acute
heart attack and electrical shock.
Figure 18.18

17. Autorythmic cells - ectopic pacemakers
Autorythmic cells of the SA node (pacemaker) may be replaced by ectopic pacemakers
Ectopic pacemakers – other parts in the heart that can induce beating
The ectopic pacemakers may become dominant:
If their rythmicity increased
The pacemaker is inhibited/blocked
The conduction system pathways are blocked
First to take over will be the AV node

19. Heart Sounds
Two sounds (lub-dup) associated with closing of heart valves
First sound occurs as AV valves close and signifies beginning of systole
Second sound occurs when SL valves close at the beginning of ventricular diastole
Heart murmurs: abnormal heart sounds most often indicative of valve problems

20. 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

21. 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

22. 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

23. 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)

24. 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

25. 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)

26. 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)

27. Effect inotropy – effect on contractility of the heart
Effect chronotropy – effect on HR
Effect dromotropy – effect on the conductive velocity
Sympathetic stimuli has a positive effect (increase) all
Parasympathetic stimuli has a negative effect (decrease) all

28. 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)

29. Autonomic Nervous System Regulation
Atrial (Bainbridge) reflex: a sympathetic reflex initiated by increased venous return
Stretch of the atrial walls stimulates the SA node
Also stimulates atrial stretch receptors activating sympathetic reflexes

30. Effects on SA node
The effect of the ANS on the heart is by changing the permeability of the conducting system cells.
Ach released by the parasympathetic neurons slow the depolarization rate and extend slightly the repolarization.
This decreases the HR
The NE released by the sympathetic neurons binds to beta–1 receptors, leading to the opening of calcium ion channels.
That increases the depolarization rate and shortens the repolarization period. Threshold is reached more quickly and HR increases

31. 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

32. 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

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

34. 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

35. 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 etc.

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

37. 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+
Calcium channel blockers

38. 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

39. 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