1. CARDIOVASCULAR PHYSIOLOGY FOR UNIVERSITY STUDENTS
S. I. OGUNGBEMI
DEPARTMENT OF PHYSIOLOGY
UNIVERSITY OF LAGOS

2. Cardiovascular System

3. INTRODUCTION
Cardiovascular system (CVS: aka circulatory system) consists of the heart and blood vessels.
The Heart
The heart is a muscular pump with 4 chambers.
The chambers are 2 atria and 2 ventricles.
The ventricles are the pumps arranged in series.
These pumps maintain continuous blood flow and blood perfusion round the body.

4. The Pump
The Heart

5. The 2 pumps are left ventricle (LV) which pumps blood to systemic circulation and right ventricle (RV) which pumps blood to pulmonary circulation.
LV output = RV output = 5000 mL/min of blood.
Heart beats at times per minute i.e. heart rate.
LV or RV output/beat = 70 mL i.e. stroke volume.
CVS circulates blood from the heart via a network of arteries, arterioles, capillaries to body tissues and
Drains blood from body tissues via venules, veins and vena cavae to the heart.

6. The Vessels
(Vascular System)

7. Thoracic Aorta

8. Superior Vena Cava

11. Major Functions of the Cardiovascular System
Transport and supply of O₂ from the lungs to the body tissues.
Extraction and transport of CO₂ from the body tissues to the lungs.
Absorption and transport of nutrients (digested food, electrolytes and vitamins) from gastrointestinal tract to the body tissues.
Extraction and transport of waste and by-products of cellular metabolism from body tissues to excretory organs: kidneys, gut, liver, skin, lungs.

12. Transport of hormones from endocrine organs to target tissues/organs.
Distribution of body heat from body’s core to its surface, aiding temperature regulation.
Transport of red and white blood cells, immune factors, playing role in defense against foreign antigens, viruses, bacteria, parasites, fungi and cancer cells.
Perfusioning of the body tissues, aiding tissue hydration.
Functional Divisions of Circulatory System
Functionally, RV runs pulmonary circulation which is in series with LV that runs systemic circulation.

13. RV is a low pressure pump which receives deoxygenated blood from superior (SVC) and inferior (IVC) vena cavae via the right atrium.
RV pumps the blood via pulmonary trunk and arteries to pulmonary capillaries surrounding the alveoli.
The blood is then oxygenated and drained into the LV via left atrium and pulmonary veins.
This is the pulmonary circulation of low pressure belt of 25 (systolic) to 10 (diastolic) mmHg.

14. LV receives the oxygenated blood and pump it to the systemic circulation via aorta, large arteries arterioles and systemic capillaries to body tissues.
In returns, the capillaries, venules and veins then drain blood from the body tissues via SVC and IVC to the right atrium.
This is the systemic circulation of high pressure belt (SBP: 120 and DBP: 80 mmHg).
The heart, especially the RV and LV, provides the propulsive force as the pump for both pulmonary and the systemic circulations.

15. Structural Function of the Heart
The heart lies slantly in the thorax in the thorax as an inverted conoid.
The superior portion where blood vessels enter and leave the heart is the BASE.
The extremity of the left ventricle is the APEX.
The heart is a hollow muscular organ which weighs about 300 or 350 g in adults.
The heart muscle is specially called cardiac muscle.
The heart is made of 4 chambers: 2 atria and 2 ventricles which lie side-by-side in series.

16. It is divided by the septum into right and left portions.
The right portion comprises right atrium and right ventricle.
The left portion comprises left atrium and left ventricle.
It is also divided into 2 atria above and 2 ventricles below by 2 atrioventricular valves on both right and left sides.
There are 4 valves in the heart: 2 atrioventricular valves described above and 2 semilunar valves at the exits of aorta on the left and pulmonary trunk on the right.
The inlet (atrioventricular) valve and the outlet (semilunar) valve of each ventricle lie along side one another.

17. So, the 4 valves lie in the same plane in the septum separating the atria from the ventricles.
The 3 Layers of the Heart
The 3 layers of the heart are:
Endocardium
Myocardium and
Epicardium
It is the inner lining of the heart.
It continues with the endothelium (i.e. the lining of the blood vessels).

18. It is the muscular layer of the heart.
Myocardium
It is the muscular layer of the heart.
It is made up of conductive and contractile cardiac tissues.
Epicardium
It is a serous layer that function as the visceral layer of the pericardium.
Pericardium
It is the conical sac within which the heart lies.
It consists of inner serous pericardium and outer fibrous pericardium.
Inner serous pericardium composed of visceral (attaching the heart) and parietal (attaching the fibrous sac) layers.

19. These 2 layers allows the heart to beat in the mediastinum with minimum friction.
Pericardium sets a limit to the maximum size of the ventricles and prevents excessive stretching of the cardiac muscle fibres during ventricular filling (with blood).
It is attached to the diaphragm, fixing the apex during each heart beat.
Thus, during ventricular contraction the base and the atrioventricular ring descends towards the apex.
This arrangement increases the size of the atria for subsequent venous return as blood is ejected from the ventricles.

20. Cardiac Valves
Cardiac valves are thin flaps of flexible, endothelium covered fibrous tissues.
They are firmly attached at the base to the fibrous valve rings.
There are 2 types of valves: the atrioventricular (AV) valves and semilunar valves.
The AV valves are the right atrioventricular (tricuspid) valve and the left atrioventricular (bicuspid or mitral) valve.
Semilunar valves are the aortic and pulmonary arterial valves

21. All the 4 valves lie in the same plane in the fibrous septum which separates the atria from the ventricles.
The movements of these valves’ flaps are passive.
The valve ensure unidirectional flow of blood through the heart without backflow.
Blood Supply to the Heart
The right and left coronary arteries and their branches supply blood to the heart.
They are the 1st branches to the heart just above the aorta.
Coronary venous blood is drained by the coronary sinus which drains into the right atrium.

22. Nerve Supply to the Heart
Sympathetic and parasympathetic nerves supply the heart.
Parasympathetic fibres supply the atria, sinus node, AV-node and conductive tissue via vagus nerve.
Sympathetic nerves are from T₁ to T₄ via inferior cervical (stellate) ganglion.
The parasympathetic supplies slow down conduction speed and heart rate.
Sympathetic nerves speed up electrical conduction, heart rate and force of contraction.

23. The heart also possess some sensory fibres for cardiovascular reflexes and pain signals.
Function Histology of the Heart
The cardiac tissue are divided into conductive tissue and contractile tissue in the myocardium.
Conductive Tissue
The conductive tissue comprises special modified nerve cells that initiate and conduct rhythmic depolarisations of the myocardial cells.
These specialised tissues are:
Sinuatrial (SA) node

24. Internodal tracts
Atrioventricular (AV) node
Atrioventricular bundle of His
Purkinje fibres
SA Node is located in the wall of right atrium (beneath the epicardium) at superior vena cava and right atrium junction
It contains the pace-maker cells that originate depolarisation and each subsequent heart beat.
AV node lies beneath the endocardium of posterior wall of the right atrium about the insertion of the tricuspid valve.
The internodal tract connects the SA node to AV node.

25. These tracts are 3:
Anterior band of Bachmann
Middle band of Wenckebach
Posterior band of Thorel
The specialised conductive cells of AV node is arranged interiorly in a longitudinal fashion to form bundle of parallel fibers called AV bundle of His.
The bundle of His divides into the right and left bundle branches.
Purkinje fibres branch off from the main bundle and supply the myocardium.

26. Bundle branches and their smaller branches constitute a fast conduction pathway through which excitation impulses are rapidly spread throughout the heart.
The Contractile Tissues
A cardiac muscle cell is called myocardial fibre or cardiac myofibril
Histology of the myocardial tissue shows that myocardial fibre is striated as it is in skeletal muscle.
These fibres are cylindrical in shape with central nuclei.
In addition to this striations, myocardial fibres are interconnected into a latticework.

27. It is difficult to see where a cell ends and another begins.
Intercalated disc separate individual myocardial fibres.
Intercalated disc has electrical conductance of 400 units greater than that of ordinary cardiac muscle membrane, i.e. its resistance is ¼₀₀ unit of myocardial membrane.
The adjacent myocardial fibre membranes fuse with each other to form “tight junctions”.
These tight junctions allow complete free diffusion of ions in and out of the myocardial fibres.
Tight junction makes the entire myocardium contracts as if it were a large sheet of muscle – i.e. functional syncytium.

28. Action potentials from adjacent cardiac myofibrils are conducted speedily through the intercalated discs and tight junctions to all cardiac myofibrils.
This leads to depolarisation of the entire heart at once.
Subsequently, the entire ventricular myofibrils also contract in synchrony in order to develop adequate expulsive force to pump out blood.
The syncytial arrangement of myocardial fibres enables the contraction wave to rapidly spread from one myofibril to another until the whole ventricular mass contracts at once.
The detail histology of the heart is given under nerve-muscle physiology.

29. Note
No nerves are involved in the spread of contraction waves throughout the myocardium.
Evidence
It has been shown that series of interdigital cuts through a piece of atrial or ventricular muscle such that could severe any nerve running in it could not prevent synchronous contraction.
Despite the cuts, application of contraction waves at one part would spread through to the whole myocardial mass producing synchronous contraction.

30. Functional Structure of the Vessels
Blood vessels are arteries and veins
In addition, there are also lymphatic vessels.
In general circulation plan:
Aorta leads from the heart to supply blood and divides to become arteries.
Arteries then divide repeatedly to become arterioles.
Arterioles divide repeatedly to become capillaries.
Capillaries unite to become venules.
Venules unite to become veins.
Veins unite to become vena cava which then returns blood to the right atrium.

31. Arteries and veins have 3-layer walls:
Tunica intima
Tunica media
Tunica adventitia
Tunica intima is the innermost layer, composed of a super-smooth epithelium called endothelium which continues with endocardium of the heart.
Tunica media is the middle layer composed of smooth muscle
Tunica adventitia is the outermost layer of connective tissues.

32. Aorta and large arteries are blood distributing or conducting vessels, distributing oxygenated blood.
They have thinner wall of smooth muscle and larger wall of elastic tissues.
They are stretched during systole but are elastically recoiled during diastole.
The elastic recoil during diastole impacts momentum to the blood flow in the arteries (impact of 40 mm Hg).
The elastic recoil results in diastolic pressure of 80 mm Hg.
The stretch/recoil cycle provides continuous blood flow in circulation.

33. Arterioles contain thick layer of vascular smooth muscles.
These smooth muscles have sympathetic and parasympathetic innervations.
Smooth muscle responds to vasoactive agents like adrenaline, noradrenaline and acetylcholine
Arterioles are the major sources of peripheral resistance to blood flow in circulation.
Alterations of arteriolar radius bring about changes in peripheral resistance, blood pressure and blood flow.
R α ¹⁄r⁴ → R = ⁿ⁄r⁴: where R = peripheral resistance; r = arterial radius; n = constant.

34. Decrease in radius (vasoconstriction) increases peripheral resistance (R) while increase in radius (vasodilatation) decreases R of the arterioles.
Decrease in R increases flow (F) and vice versa
Increase in R or F increases mean arterial pressure (P)
Capillaries are the smallest vessels with diameter of about 8 μm.
They are one cell thick endothelial wall but just large enough for an RBC to pass through at once.
Capillaries are sites of exchange of substances between blood and tissue cells.

35. Filtration occurs at the arterial end of the capillaries (mostly O₂ and nutrients, ions, hormones)
Reabsorption occurs at the nervous end (removing CO₂, waste products and metabolites)
Veins are blood drainage vessels, draining and returning blood into the heart.
They return deoxygenated blood to the heart.
They are thinned-walled low pressure and cylindrical distensible vessels.
They are capacitance vessel containing about 75% of the entire circulating blood volume.

36. Some veins have one-way valves which prevent reflux of blood flow as they drain blood against gravity.
They possess sympathetic innervation which maintains the venomotor tone.
Venules are the smallest veins with less prominent muscular walls than those of arterioles.

37. PHYSIOLOGICAL PROPERTIES OF THE HEART
Physiological properties that are peculiar to cardiac tissues/cells are listed below as follow:
Spontaneous and automatic cardiac rhythmicity
Length-Tension relationship
Prolonged repolarisation of action potentials
Absolute refractoriness
Functional syncytium nature of cardiac myofibril
Obeys all or none law
Double innervation
Note: the 6th property is common to skeletal muscle or nerve cell and 7th property is common to some visceral tissues as well.

38. Length-Tension Relationship
If the length of a cardiac myofibril is increased, the force of contraction also increases.
Starling’s law states that the force of contraction of cardiac myofibril is proportional to its extension and initial length.
The initial length is the resting length before the extension of the cardiac myofibril or muscle fibre.
These fibres are extended by blood filling the ventricles i.e. blood volume exerts tensions on the heart muscle fibres.
In addition at resting length, these cardiac myofibrils assume sarcomere length for maximal contraction.

39. This extension by the filling blood volume stores up potential energy which is kinetiated into contraction (mechanical energy).
This energy from mas to ½κε² means mas = ½κε²
κ = extension constant
ε = extension of the myocardial fibre
m = mass of the myocardial fibre
a = acceleration of the myocardial fibre during contraction.
s = distance covered by the myocardial fibre during contraction.

40. The force of contraction is increased by positive inotropic agents like Ca²⁺, adrenaline, noradrenaline, thyroxine etc.
On the other hand, the force of contraction is reduced by negative inotropic agents like K⁺, acetylcholine etc.
Note
Excess Ca²⁺ will make the heart to stop working at systole (i.e. cardiac arrest at systole).
Excess K⁺ will make the heart to stop at diastole (i.e. cardiac arrest at diastole).

41. Spontaneous and Automatic myocardial Rhythmicity
Inherently, the heart is able to initiates its own electrical excitation, contraction and heart beat without nervous or humoral stimulation from any tissues outside itself.
So the cardiac myofibrils contract (at systole) and relax (at diastole) alternately in a rhythmic manner inherently.
Conductive tissues which produces spontaneous excitation and contraction are the source of this ability of the heart.
The conductive tissues are the SA and AV nodes, bundle of His and Purkinje fibres.

42. Prolonged Repolarisation
The action potential in the myocardial or contractile cells lasts about 300 msec unlike the 2 msec in skeletal muscle.
This is due to the fact that repolarisation phase of the action potential (AP) is prolonged in cardiac muscle cells.
Slow influx of Ca²⁺ or slow inward Ca²⁺ current is responsible for the prolonged repolarisation phase.
Ca²⁺ moves slowly inside cardiomyocytes to produce the plateau, resulting in persistent depolarisation during the prolonged repolarisation phase of cardiac AP
This persistent depolarisation is a positive membrane potential during repolarisation phase cardiac myocytes.

43. Ca²⁺ influx is via potential sensitive channels (PSC) of the cardiacmyocytes which opens during electrical excitation.
Ca²⁺ also flux in via receptor operated channels (ROC) which are sensitive to noradrenaline, adrenaline (agonists).
Influx of ISF Ca²⁺ stimulates the release of more Ca²⁺ᵢ from sarcoplasm reticulum which then induce cardiac muscle contraction.
Ca²⁺ channels blockers like verapramil or nifedipine inhibit Ca²⁺ entry following depolarisation of the myocardial cells.

44. Functional Syncytium Myofibrils
The cardial myocytes function like a syncytium.
Because the whole ventricular or atrial myofibrils contract at once as if they were one myofibril.
Cardiac myofibrils possess intercalated disc, tight and gap junctions which make them to contract as a syncytium.
Absolute Refractoriness
A second excitation cannot cause the cardial myocytes to depolarise or contract while the first excitation in process.
Therefore, the heart muscle cannot tetanise, because its action potential (AP) is prolonged and the period of contraction is as long as the duration of its AP.

45. The prolonged absolute refractoriness makes it impossible for the heart muscle to tetanise.
Obeys “All” or “None” Law
Cardiac myofibril does not possess graded excitation.
These myofibrils are only excited to produce an AP (“all” part of the rule) by a threshold or suprathreshold stimulus.
On the other hand, the myofibrils are not excited by subthreshold stimulus (the “none” part of the rule).
Cardiac myofibrils doesn’t exhibit recruitment of fibres with increase in stimulus strength unlike skeletal muscle.

46. CARDIAC ELECTROPHYSIOLOGY
Origin of the Heartbeat
The 2 atria and the 2 ventricles beat in orderly rhythm as atria systole is followed by ventricular systole.
Systole of atria and ventricles occurs one after the other respectively and is followed by diastole in orderly rhythm.
The heartbeat ORIGINATES in a specialised cardiac conducting system comprises modified nerve tissues.
The conductive system generates and transmits electrical current or action potential (AP) from one point to another and to all part of the myocardium.

47. The tissues that make up the conduction system are:
Sino-atria node (SA node)
3 atria internodal pathways
Atrioventricular node (AV node)
Bundle of His and its branches
The Purkinje system
The SA node is the cardiac pacemaker, since it originates AP spontaneously and automatically and spread to all other conductive tissues and myocardium.
Other conductive tissues and myocardium are induced in this way to generate and transmit impulses.

48. SA node discharges AP most rapidly than AV node, conductive fibres and myocardial fibre.
SA node firing rate superimposes those of all others, making them to discharge at the same rate with SA node.
SA nodal rate equals heart rate as the pacemaker.
AP generated in the SA node spread through the atrial pathways to the AV node.
AV node then spread AP via His bundle and its branches.
Finally, AP is spread to the ventricular muscles (for contraction) via Purkinje fibres.

49. Origin and Spread of Cardiac Excitation
P (pacemaker) cells produce AP in the SA node.
They are small round cells (with few organelles) joined by gap junction and found in large population in SA node.
They are also found in AV node but in a lesser population.
SA nodal P cells send AP radially via the atria to converge on the AV node through:
Anterior internodal tract of Bachman
Middle internodal tract of Wenckebach
Posterior internodal tract of Thorel and
Slow atrial myofibrils.

50. The atrial depolarisation is complete within 0.1 s.
In the AV node, depolarisation is then sent to the ventricles with a slow conduction of 0.1 s delay.
Sympathetic stimulation hastens the conduction, shortening the delay while vagal stimulation lengthens the conduction, prolonging the delay.
Depolarisation waves then further spread from the top of interventricular septum in the Purkinje fibres rapidly to all parts of the ventricles within 0.08 – 0.10 s.
This depolarisation is so rapidly spread in the His bundle-Purkinje fibres and ventricular muscle mass.

51. Depolarisation wave is of similar shape, duration and amplitude in His bundle-Purkinje and ventricular fibres.
In the human hearts, ventricular depolarisation starts at the left side of the interventricular septum, and then moves to the right across mid-portion of the septum, spreading down to the heart apex (base → apex).
The wave returns along the ventricular walls to the AV groove, from endocardial to epicardial surface and to the posterobasal of the ventricle, pulmonary conus and uppermost portion of the septum.
Ventricular depolarisation is from left to right side (after which impulses travel to the apex) while ventricular repolarisation occurs in reverse direction (apex → base).

52. Note
Bundle of His and Purkinje fibres are normally quiet and are just latent pacemakers.
However, they are capable of spontaneous discharge only if they are damaged.
Atrial and ventricular myofibrils also do not discharge spontaneously unless they are injured.
Sinoatrial (SA) node discharges at 70/minute.
Atrioventricular (AV) node discharges at 50/minute.
Bundle of His-Purkinje fibre discharges at 45/minute.
Ventricular myofibril discharges at 40/minute.

53. Action Potentials in Cardiac Cells
Cardiac action potentials (AP) are generated in:
Pacemaker or Conductive cells
Atrial cells and
Ventricular cells
Pacemaker SA and AV nodal cells AP are similar
Atrial, His bundle, bundle branch, Purkinje fibre and ventricular AP are similar.
Generation of Action Potential in Pacemaker Cells
Pacemaker potentials are largely found in SA and AV nodes

54. Pacemaker potentials are pre-potentials that trigger another AP following a previous AP.
Pre-potentials are declinations of membrane potentials from resting membrane potential (RMP: -60 mV) to firing level (-40 mV) in pacemaker cells (magnitude of +20 mV).
Depolarisation Phase
After a previous AP in a pacemaker cell, h or f channels which are permeable to Na⁺/K⁺ are opened.
Influx of Na⁺ depolarise the pacemaker membrane – first portion of pre-potentials, prominent in SA and AV nodes.
Transient (T) Ca²⁺ channels are later opened to produce Ca⁺⁺ influx (ICa²⁺) to complete the pre-potentials.

55. There is also release of Ca²⁺ from sarcoplasmic reticulum during pre-potentials.
After the pre-potentials, longlasting (L-) Ca²⁺ channels are then opened to cause Ca²⁺ to produce depolarisation.
Subsequently, pacemaker depolarisation is slow but not rapid or sharp before the plateau.
Repolarisation Phase
At the peak of the pacemaker AP following the brief plateau of ICa²⁺, there is opening of K⁺ channels.
This then leads to increase in gK⁺ and influx of K⁺ and subsequent repolarisation and hyperpolarisation.

56. Following hyperpolarisation, IK⁺ or K⁺ influx declines to activate h or f channels, bringing about another pre-potential and depolarisation in the pacemaker cell.
Effect of Cholinergic and Vagal Stimulation
Hyperpolarisation of pacemaker membrane with a slow and decreased slope of pre-potential.
Release of acetylcholine at the nerve endings
Increase gK⁺ of nodal tissue cells.
Depolarising effect is slowing down the heart rate.
Note: M₂ muscarinic receptor and decrease in cAMP is responsible for these vagal effects.

57. Effect of Sympathetic Stimulation
Speeds up gNa⁺ and gCa²⁺ via h- and T- channels respectively.
Speeds up depolarisation spike frequency via L-channels.
Stimulate β₁ receptors to produce increase heart rate.
Noradrenaline and increase cAMP facilitates opening of L-channels.
Further Information
Temperature or fever increases discharge frequency of SA and AV nodes to produce increase in heart rate.
Digitalis depresses nodal tissues particularly on AV nodes, exerting vagal like effects.

58. Digitalis (i.e. digoxin and digitoxin) depresses nodal tissues particularly on AV nodes to exert vagal-like effects.
Digitalis is a known treatment for systolic heart failure.
It augments ventricular contractility.
It improves left ventricular emptying and cardiac output.
It decreases ventricular filling pressure.
It’s useful to treat atrial fibrillation and flutter by reducing heart rate and frequency of AP transmission through AV node and heart rate. via
Digoxin and digitoxin strengthens cardiac contraction through the inhibition of Na⁺/K⁺ ATPase.

59. This is achieved via greater release of Ca²⁺ and subsequent improvement in contraction force.
Digitalis decreases AV nodal conduction velocity in order to improve transmission to the ventricle.
Artificial Pacemaker
Artificial pacemaker is invaded under the chest skin below the clavicle to help moderate heart rate and contractility.
It generates electric current to stimulate atria and ventricles.
It has a pulse generator with one or more leads, powered by a very reliable lithium battery.

60. It lasts for many years about a size of 50 kobo coin.
The leads connect the pulse generator to the inner wall of the heart.
The leads are made up of insulated metal coils with small metal electrodes that attached to the heart.
Types of artificial pacemakers are single chamber, dual chamber and biventricular pacemakers.
Single chamber pacemaker sets the pace of the left ventricle and uses 1 lead.
Dual chamber pacemaker sets the pace of 2 heart chambers and uses 2 leads.

61. It uses atrial electrical feedbacks to set the ventricular rate.
It is very useful in the management of heart block.
Biventricular pacemaker uses 3 leads for right atrium, right and left ventricles.
Artificial pacemakers are needed in management of bradycardia, tachycardia, heart block and heart failures, neurogenic syncope.
It changes the atria and ventricles to pump blood at a normal volume and rate.
It senses and moderates the heart natural rhythms in case of bradycardia and tachycardia, but switches off in normal heart condition.

62. Typical Cardiac Action Potential
Typical cardiac action potential (AP) is found in atrial and ventricular myofibrils, His bundle and Purkinje fibres.
Atrial and ventricular myofibrils produces no prepotentials nor spontaneous discharge except in injurious conditions.
His bundle and Purkinje fibre are latent pacemakers which neither produce pre-potentials nor spontaneous discharge except when SA and AV nodes are blocked.
Ventricular myofbril (or myocyte) action potential is here presented as the typical cardiac AP for atrial, His bundle and Purkinje Cells.

63. SA and AV nodes then spread depolarisation to His bundle, Purkinje and ventricular cells to generate action potential.
Generation of AP is discussed under 5 phases.
Depolarisation phase 0
Initial repolarisation phase 1
Plateau phase 2
Final repolarisation phase 3 and
RMP phase 4
Depolarisation Phase
As the cardiac myocyte membrane becomes excited, there is increase in gNa⁺ and Na⁺ influx into the cardial myocyte via the voltage gated Na⁺ channels.

64. This Na⁺ influx produces depolarisation of the cardial myocyte from RMP of -90 mV until depolarisation of +15 mV (at -75 mV of the membrane potential) is reached.
This depolarisation of +15 mV is the firing level (FL).
At the FL, there is a spark of Na⁺ influx because numerous thousands of voltage-gated Na⁺ channels are opened.
The membrane is then further depolarised from FL to peak potential (+35 mV) through the zero potential.
This is depolarisation phase 0.
The next is repolarisation phases 1, 2 and 3.

65. Repolarisation Phase
After a time lapse, an initial rapid repolarisation phase 1 is produced due to 2 events:
Closure of voltage-gated Na⁺ channels and the subsequent reduction in gNa⁺/Iɴₐ⁺
Transient efflux of K⁺ via K⁺ channels.
Instantly, gCa²⁺ increases and Ca²⁺ influx into cardial myofibrils via voltage- and ligand-gated Ca²⁺ channels.
The slow Ca²⁺ influx overbalance K⁺ efflux to produce persistent depolarisation during the repolarisation phase.
This persistent depolarisation owing to slow ICa²⁺ causes the plateau that prolong the repolarisation phase.

66. This Ca²⁺ influx (from ISF) also stimulates the release of Ca²⁺ from sarcoplasmic reticulum of the cardial myofibril.
The resultant 1000 fold increase in ICF Ca²⁺ then brings about the initiation of muscle contraction.
Ca²⁺ blockers (verapramil and nifedipine) reduce influx of Ca²⁺ (at the plateau) and the cardiac contractility.
The final repolarisation is produced by the K⁺ efflux via multiple types (especially) voltage-gated K⁺ channels.
There is also inactivation of Ca²⁺ channels and inhibition of Ca²⁺ influx during the final repolarisation phase.
The membrane potential is then brought from peak potential (+35 mV) to RMP (-90 mV).
Cardiac action potential takes about 300 ms.

67. ELECTROCARDIOGRAMME (ECG)
Electrocardiogramme is the extracellular recording of the combined voltage produced from the electrical activities of cardiac muscle cells during each cardiac cycle.
ECG gives the algebraic sum of the cardiac action potentials of all the cardiac muscle fibres from different regions of the heart during each cardiac cycle.
This characteristics sequence of potentials are generated by the heart during each cardiac cycle.
Since the ISF surrounding the heart is an electrolyte and electric conductor the body is a volume conductor of electric current.

68. This cardiac voltage or potential or ECG can be picked up on the body using extracellular electrodes, because the body is a volume conductor of electricity.
This cardiac voltage becomes much attenuated by the time it reaches the surface of the skin.
So, ECG machines picks up this cardiac voltage using amplifiers before it is recorded on moving strip of paper.
The paper is ruled in mm²: 10 mm = 1 mV on the voltage (“y”) axis and 25 mm = 1 s on the interval (“x” axis).
ECG tracing contains P, Q, R, S, T and u waves on ruled paper with each letter wave representing a depolarisation or repolarisation of different regions of the heart.

69. Measurement of Electrocardiogramme ECG is measured using ECG machines.
ECG limb leads are metal plates connected to ECG machine that are strapped over the flat portion of the limb.
ECG chest leads are small metal pots connected to ECG machine that are attached to 6 positions on the chest.
Electrode jelly is applied on the electrodes to ensure good electrical connection.
The 3 types of ECG leads used in recording ECG are:
Standard limb leads which are bipolar leads
Augmented unipolar limb leads
Chest or precordial leads which are unipolar leads

70. Standard Limb Leads
An electrode connects the right leg to the earth.
The 3 leads in standard limb leads are numbered I, II, III.
ECG from these 3 leads are recorded by connecting the appropriate pair of electrodes to the amplifier.
Lead I measures ECG voltage between right arm (RA) and left arm (LA).
Lead II measures ECG voltage btw RA and left leg (LL).
Lead III measures ECG voltage between LA and LL.
Summary: lead I → RA//LA; lead II → RA//LL and lead III → LA//LL

71. Augmented Unipolar Limb Leads
This is an alternative way of measuring ECG.
One input of the amplifier is connected to the other 2 limbs via 2 resistors.
This records difference between potential in 1 limb and the mean potential of the other 2.
aVR is the lead attached to right arm (- deflection).
aVL is the lead attached to left arm (+ deflection).
aVF is the lead attached to the left foot (+ deflection).
a = augmented; V = voltage

72. The augmented leads increase the size of the potential by 50% without any change in configuration from the non-augmented records ie aV = ³/₂ of unaugmented lead.
Unipolar Chest Leads and Limb Leads
Chest and limb lead ECG are recorded by connecting the amplifier between exploring chest electrodes and resistances connected to 3 limbs as indifferent electrodes.
The 6 chest leads with their 3 aV limb leads, making 9 leads are commonly used in clinical electrocardiography.
Chest leads and their recordings are designated V₁, V₂, V₃, V₄, V₅ and V₆ while the aV limb leads and their recordings are designated aVR, aVL and aVF.

73. Amplifier converts the 9 unipolar to augmented leads by increasing voltage amplitude by 50% without any change in configuration from the nonaugmented recording.
Anatomical location of chest lead positions are as follows:
V₁ → 4th intercostal space immediately to the right of sternum.
V₂ → 4th intercostal space immediately to the left of sternum.
V₃ → midway between V₂ and V₄
V₄ → 5th intercostal space in the left mid-clavicular line, corresponding to the apex of the heart.

74. V₅ → 5th intercostal space in the left anterior axillary line in the same horizontal plane as V₄.
V₆ → 5th intercostal space in the left mid axillary line in the same horizontal plane as V₄.
Normal Electrocardiograph Wave Movement
The important consideration in interpreting the configurations of the waves in each lead depends on:
The sequence in which the parts of the heart are depolarised.
The position of the heart in relative to the electrodes.
The atria are located posteriorly in the chest while the ventricles form the base and anterior surface of the heart.

75. The right ventricle is anteriolateral to the left ventricle.
Left ventricle is posteriolateral and form the apex of heart.
The aV Limb Leads
aVR looks at the cavities of the ventricles.
Atrial and ventricular depolarisations and repolarisations move away from the exploring aVR electrodes
Therefore P, QRS and T waves are all negative or downward deflections in aVR lead.
aVL and aVF leads look at the ventricles
Atrial and ventricular depolarisations and repolarisations move towards the exploring electrodes aVL and aVF

76. Therefore P, QRS and T waves or deflections are predominantly positive or biphasic in aVL and aVF leads.
The Chest Leads and Standard Limb Leads
There is no Q wave in V₁, V₂ and V₃ and initial portion of the QRS complex (i.e. R wave) is a minor upward wave.
Ventricular depolarisation first moves across the mid-portion of intraventricular septum from left to right towards the exploring V₁, V₂ and V₃ electrodes
Then, depolarisation wave moves down the septum and into left ventricle, but away from electrodes to produce a large S wave.
Wave lastly moves along the ventricular wall and towards exploring V₁, V₂ and V₃ electrodes to iso-electrical line.

77. Conversely, in the left ventricular leads, (V₄−V₆), there may be initial small Q wave.
Q wave represents left to right septal depolarisation.
There is also a large R wave which represents septal and left ventricular depolarisation.
R wave in V₄ and V₅ is followed by a moderate S wave which represents late depolarisation of the ventricular wall moving back towards the AV junction.
Note: there is considerable variation in the position of normal heart which affects ECG QRS complex in various leads.

78. Deflection of P, QRS and T waves in V₁, V₂, and V₃ are negative as these waves of depolarisation are moving away from the position of the V₁, V₂, and V₃ leads.
The deflection of P, QRS and T waves in leads V₄, V₅ and V₆ and I, II and III are similar and positive.
These waves of depolarisation are moving toward the position of leads V₄, V₅ and V₆ and I, II and III.
Cardiac Vector
An approximate mean QRS vector (electrical axis of the heart) is often plotted by using the average QRS voltage in each lead.

79. Approximation is done by recording net difference btw the positive and negative peaks of the QRS complex.
The normal direction of the mean QRS vector is taken as -30 to +110 degrees on the co-ordinate system.
Left axis deviation is presented if the calculated axis falls to the left of -30 degree.
Right axis deviation is presented if the calculated axis falls to the right of +100 degree.
Left axis deviation mean to left ventricular hypertrophy (LVH), but there are more reliable ECG criteria for LVH.
Right axis deviation suggest right ventricular hypertrophy.

80. The mean electrical axis of the heart is calculated from Einthoven’s triangle.
The mean QRS vector in I, II and III are calculated.
The values are plotted on appropriate axis of equilateral triangle with perpendicular bisector to the to the centre.
The point of intersection of the vectors values is joined to the centre of the circle by a line.
Therefore, the angle this line makes with the horizontal is the mean axis.
Vectorcardiogrammes of P, QRS and T waves are now been done electronically and projected on the screen.

81. The Synchrony of Cardiac Electrical Activities
The figure below shows the synchrony of order, timing, strength and duration course of individual cardiac cell action potentials (AP) relative to the ECG waves.
Production of APs in cardiac cells are in the order of: SA node, atrium, AV node, His bundle, bundle branches, Purkinje fibres and ventricular myofibrils.
Meanwhile, depolarisation and repolarisation phases of these APs from different heart portions synchronise in order, timing and duration with:
One another i.e. individual APs
ECG depolarising and repolarising waves and
Cardiac cycle.

82. SA nodal depolarisation begins the electrical activity at say time 0 s and its repolarisation lasts till 0.22 s after.
Depolarisation of SA node is 0.08 s earlier than atrial depolarisation and P wave on ECG tracing.
Atrial depolarisation starts 0.08 s after SA node and its repolarisation lasts till 0.25 s after the depolarisation.
Atrial depolarisation starting time correspond with that of P wave on ECG tracing.
AV node depolarisation begins at about 0.12 s after that of SA node following atrial depolarisation and corresponds to the peak of P wave.

83. AV node depolarisation lasts till 0
AV node depolarisation lasts till 0.24 s from the start of depolarisation.
His bundle and branches and Purkinje fibre also begin depolarisation at 0.2, 0.22 and 0.24 s respectively following SA node depolarisation.
Depolarisations of these fibres occur during PR segment (no ECG wave but isoelectric line).
Their repolarisation last till 0.32 s after depolarisation.
Depolarisation of ventricular muscle fibre begins at 0.24 s after SA node depolarisation (i.e s after P wave onset) and its repolarisation lasts till 0.32 s after.

84. The depolarisation of His bundle, Purkinje fibre and ventricular myofibril produce the QRS complex.
Their persistent depolarisation phase of the prolong repolarisation produces and corresponds to the isoelectric line of ST segment.
Their final repolarisation phase produces and corresponds to T wave.
The prolonged repolarisation also corresponds to the ventricular systole.
This synchrony of the electrical activities of individual heart portion is possible owing to the syncytium property of the heart via intercalated disc and gap junction.

85. Interpretation of ECG Tracing
P wave (+) represents atrial depolarisation, because it is produced by atrial depolarisation.
QRS wave (+) represents ventricular depolarisation, because it is produced by ventricular depolariastion.
T wave (+) represents ventricular repolarisation, because it is produced by ventricular repolarisation.
Q wave (-) is produced by depolarisation of the middle ⅓ of interventricular septum.
R wave (+) is produced by lower ⅓ of interventricular septum and lower ⅔ of right and left ventricles.

86. S wave (-) is produced by upper ⅓ of interventricular septum and upper ⅓ of right and left ventricles.
U wave (+) is produced by depolarisation of the papillary muscles – an inconstant finding.
Note: – wave produced by atrial repolarisation is not normally seen, because it is superimposed by the larger QRS complex.
Therefore, the unseen wave of atrial repolarisation is buried in the QRS complex.
S wave in V₁−V₃ appears to be a mirror image of R wave in V₄−V₆
PR interval is the period for atrial depolarisation and conduction of AP from atria via AV node to the ventricles.
PR interval also measures the period for the following events, which occur during PR interval:

87. The spread of atrial depolarisation wave to the vicinity of AV node.
The delay imposed by AV node – the main delay
The rapid spread of depolarisation from AV bundle and its branches
QRS duration is the period for ventricular depolarisation (i.e. spread of AP) and atrial repolarisation (Q wave)
QT interval is the period for ventricular depolarisation plus atrial and ventricular repolarisations.
QT then stands for the duration of the AP in the ventricles.
ST interval is the period for ventricular repolarisation.

88. P wave amplitude is normally 0.1-0.2 mV
R wave amplitude is normally 1 mV
Q wave amplitude is normally mV
S wave amplitude is normally 0.3 mV in V₄-V₆ chest and limb leads.
T wave amplitude is normally 0.3 mV.
QRS wave amplitude greater than 5 mm or 0.5 mV is written in capital Letter e.g. Q, R and S.
QRS wave amplitude lesser than 5 mm or 0.5 mV is written in small letter e.g. q, r and s.
P wave duration is about 0.1 s.
PR interval is about 0.18 s.

89. QRS duration is about 0.1 s
QT interval is about 0.40 s
ST interval is about 0.32 s.
T wave duration is about 0.18 s
A Physiologist or Physician should be able to derive the following from an ECG tracing:
Heart rate
Cardiac rhythm
Electrical axis of ECG waves/anatomical orientation of the heart
Heart block

90. Hypertrophy/relative size of the heart
Myocardial ischaemia
Accelerated conduction
Arrhythmias
Heart Rate
Heart rate (HR) is calculated as 25 ÷ RR interval × 60
If RR interval = 20 mm? HR = 25 × 60 ÷ 20 mm = 75 bpm
In normal sinus rhythm (NSR), HR ranges 70 to 75 bpm.
HR decelerates during sleep, expiration and accelerates by emotion, exercise, fever, inspiration.

91. Cardiac Rhythm
The source of heart electrical activity is cardiac rhythm.
A sinus (or atrial) rhythm originates from the SA node.
A junctional rhythm originate from the AV node.
A ventricular rhythm originates from the ventricles.
Characteristics of Sinus Rhythm
Every QRS complex is preceded by a P wave.
The P waves in successive cardiac cycles are of uniform morphology with little or no variations.
The P waves are upright (positive) in the leads.

92. The cardiac rate does not fall below 60 or above 100 bpm – physiologic range.
The PP or RR interval are constant with difference not exceeding 0.12 s (or 3 mm).
Conditions 1-5 is called normal sinus rhythm.
In sinus arrhythmia, conditions 1-3 are met but the difference in the PP or RR intervals not differ from 0.12 s.
In sinus bradycardia, the rate is below 60 while in sinus tachycardia, it exceeds 100 bpm.
Atrial rhythm is practically indistinguishable from sinus rhythm in the physiological range.

93. Characteristics of Junctional Rhythm
In junctional rhythm, the rate is between 40 and 60 bpm.
Its P wave is usually inverted, preceding, coinciding with or following QRS complex.
It is described as slow junctional tachycardia between 60 and 100 bpm in spite of the physiologic range.
Above 100 bpm, it is described as accelerated junctional tachycardia.
Young adults/athletes have SAN and AVN functioning competitively at similar rate – isorhythmic rhythm.

94. Sometimes in alternation with AVN in control and at other times the SAN in control.
Characteristics of Ventricular Rhythm
Rate is bpm (idioventricular rhythm)
Absent P waves
Wide QRS complex with duration exceeding 0.12 s
Ventricular rate between 50 and 100 is described as accelerated ventricular rhythm.
ECG Axis of the Heart and Associated Conditions
Electrical axis of the heart is classified as:
Normal axis (within 0° to +90° or -30° to +110°)

95. Left axis deviation (LAD: 0° to -90° or left of -30°)
Right axis deviation (RAD: +90° to +180° or right of +100°)
Indeterminate axis (-90 to -180°)
About 97% of normal Nigerians fall in the normal range of electrical axis.
2.9% of normal Nigerian fall in LAD
0.1% of normal Nigerian fall in RAD and
Indeterminate QRS axis is extremely rare in normal subjects.

96. The following conditions are associated with LAD:
Heart block
Myocardial infarction or ischaemia
Emphysema
Congenital heart disease
Hyperkalaemia
Ageing
Male sex
Conditions associated with RAD:
Normal variation
Right ventricular hypertrophy
Right ventricular conduction defect
Dextrocardia
Inspiration

97. ECG Pathophysiology
Abnormal Pacemakers: they arise with damage to SA or AV nodes
Diseased or injured atrial and ventricular myofibrils can act as abnormal pacemakers.
Incomplete heart block is due to slow conduction between atria and ventricles.
1st degree heart block is due to prolong nodal delay (PR > 0.20 s prolong nodal delay) with P wave : QRS = 1 : 1
However, in first degree heart block, all the atria impulses reach the ventricles.

98. In 2nd degree heart block, not all atrial impulses are conducted to the ventricles.
A ventricular beat may follow every 2nd or 3rd atrial beat i.e. P wave:QRS wave = 2:1 or 3:1 block.
In Wenckebach phenomenon: repeated sequence of beats with progressively prolonged PR interval until a QRS and ventricular beat is dropped.
The PR interval that follows each QRS or dropped beat is usually normal or slightly prolonged.
Right or left bundle branch block is due to interruption of His bundle with deformed and prolonged QRS (>0.1 s) depolarisation but normal ventricular rate or P:QRS.

99. Hemiblock or Fascicular block occurs on the anterior or posterior fascicle of left bundle branch.
Left anterior hemiblock produces abnormal LAD on ECG whereas left posterior hemiblock produces abnormal RAD.
Combination of fascicular and branch blocks produces bifascicular or trifascicular block.
Complete heart block fully interrupts conduction from atria to the ventricle by AV nodal or infranodal block.
The ventricle beats at idioventricular rhythm of low rate (43/min) independently of the atria (107/min).
Independent P and QRS wave on ECG wave with regular PP or RR interval but with irregular PR interval.

100. Ectopic beat is extra premature beat which (transiently interrupts cardiac rhythm) is produced before normal beat.
There exists atria, nodal and ventricular extra systole or premature beats.
Ectopic beat that is produced at regular but higher rate than that of SA node could be atria, ventricular or nodal paroxysmal tachycardia or atrial flutter.
Atrial tachycardia is about 220/min.
Atrial flutter rate is /min
Atrial fibrillation is /min and there is no P but F (saw-teeth) wave which is rapid and irregularly irregular.

101. Long QT Syndrome
It occurs when the QT interval is prolonged > 420 ms.
It indicates heart vulnerability due to irregular repolarisation.
There heart is vulnerable to increase frequency of ventricular arrhythmias and sudden death.
It is caused by different drugs, electrolyte abnormalities and myocardial ishaemia or congenital factor.
Mutations of 8 different genes have been reported to cause long QT syndrome.

102. 6 caused reduced functions of various K⁺ channels by structural deformation.
1 inhibits a K⁺ channel by reducing the amount ankyrin isoform that link it to the memebrane cytoskeleton.
1 increases the function of cardiac Na⁺ channel.

103. Ventricular Fibrillation
The fibrillated ventricular muscle fibres contract in a totally irregular and ineffective way.
Ventricular fibrillation follows electric shock or ventricu- lar extrasystole and coincides with midportion of T wave.
Some ventricular myocardium is depolarised, incomple- tely repolarised and completely repolarised.
Fibrillating ventricle cannot pump blood effectively (no heart beat or QRS wave) and that stops blood circulation.
Fibrillation lasting more than a few minutes is fatal most frequently in myocardial infarction.

104. Cardiopulmonary Resuscitation
Defibrillators produce electrical shocks for defibrillating a stopped or fibrillating heart in patients.
Cardiac output and perfusion of the coronaries can be partially maintained by closed-chest cardiac massage.
Defibrillators can also be implanted surgically in patients at high risk for ventricular fibrillation.
Defibrillators are programmed to discharge automatically after 5-10 s of ventricular tachycardia or fibrillation.
Cardiac massager places heel of one hand on the lower sternum, above xiphoid process, and the heel of the other hand on the first hand.

105. Pressure is applied straight down, depressing the sternum 4 or 5 cm toward the spine.
This procedure is done times/minute.
Whenever the heart suddenly stops, the pulmonary veins, left heart and arteries still are full of oxygenated blood.
Therefore, the attention is shifted to circulation.
However, if respiration also stops full cardiopulmonary resuscitation should be applied.
In this case, cardiac compression should be alternated with mouth-to-mouth breathing at a rate of 1 ventilation to 5 Compressions.

106. Abnormalities of membrane polarisation associated with acute myocardial infarction

107. Cardiac Cycle
Introduction

108. Mechanical Phases during Cardiac Cycle
Mechanical events of the cardiac cycle occurs during:
Late diastole
Atrial systole
Ventricular systole
Early diastole
Events in Late Diastole
Mitral and tricuspid valves btw atria and ventricles opened.
Aortic and pulmonary valves are closed.
Blood flows into the heart throughout the diastole, filling atria and ventricles.

109. Rate of filling declines as the ventricles become distended, especially when the heart rate is low, because the cusps of atrioventricular valves drift towards the closed position.
The atrial pressure is 4 mm Hg which exceeds ventricular pressure (0 mm Hg) promotes the ventricular filling.
Events in Atrial Systole
The 2 Atria contract during atrial systole.
Atrial depolarisation leads to atrial contraction or systole.
Atrial contraction produces rise in atrial pressure, increase in AV valves (leaflet) diameter (separation) and ejection of blood into the ventricles.

110. Atrial contraction propels 30% blood into the ventricles at ⅟10 before the onset of systole.
70% of ventricular filling occurs passively during diastole as a result of the pressure gradient.
Atrial contraction narrows superior and inferior vena cavae and pulmonary veins orifices.
Atrial contraction is not essential for life, but the heart is a much more efficient pump when the atria are contracting.
The inertia of blood that moves blood towards the heart also keep the blood in the heart.
However, there is some regurgitation of blood into the veins during atrial systole.

111. The pressure in the atria produces a curve that shows “a”, “c”, and “v” waves and the “x” and “y” descents.
The “a” wave is the increase in atrial pressure produced by atrial contraction.
The “c” wave is the slight increase in atrial pressure produced by ventricular contraction.
At this “c” wave point, AV valves bulge into the atria, producing the 1st heart sound.
The “x” descent is caused by the pulling down of the AV valves by the contracting ventricles.
The “v” wave is produced by atrial filling (i.e. subsequent

112. increase in atrial pressure) and reaches a peak in late ventricular systole while the AV valves are closed.
The “y” descent is produced by fall in atrial pressure following opening of AV valves and ventricular filling.
Pressure changes in the right atrium are communicated to the great veins so that the “a”, “c” and “v” waves together with “x” and “y” descents are seen in the jugular veins.
Jugular venous pressure is then a useful clinical index of functional activity of the heart, especially the right pump.
The period between the end of “a” wave to the beginning of another “a” following “y” descent is the atrial diastole.

113. The jugular pulse wave are superimposed on the respiratory fluctuations in venous pressure.
Venous pressure falls during inspiration (resulting from increased negative intra-thoracic pressure) and rises again during expiration.
Giant “c” wave is produced with each ventricular systole in tricuspid valve insufficiency.
Giant “a” wave is produced whenever the atrial contracts while the tricuspid valve is closed.
Atrial premature beat (or extrasystole) produces an “a” wave whereas ventricular extrasystole beat does not.

114. In complete heart block, atria and ventricles beat at different rate, such that waves that are not synchronous with the radial pulse are made out.
Event in Ventricular Systole
At the start of ventricular systole, the AV valves close.
Ventricles initially contract little, but intraventricular pressure rises as ventricles press the blood in it.
This is the period of isovolumetric ventricular contraction, lasting about 0.05 s.
Following isovolumeric contraction, pressures in the left and right ventricles exceed pressures in the aorta (80 mm Hg) and pulmonary artery (10 mm Hg) respectively.

115. So, aortic and pulmonary valves open and the bulging of AV valves into atria causes a sharp rise in atrial pressure.
Opening of the aortic and pulmonary valves begins the phase of ventricular ejection of blood.
Ejection of blood is rapid at first but slowing down as systole progresses.
The intraventricular pressure rises to a maximum and then declines somewhat before ventricular systole ends.
Peak left ventricular pressure is about 120 mm Hg, and peak right ventricular pressure is 25 mm Hg or less.
Late in systole, aortic pressure exceeds ventricular, but for a short period momentum keeps blood moving forward

116. The AV valves are then pulled down by the contractions of the ventricular muscle, and atrial pressure drops.
Finally, the amount of blood ejected by each ventricle per stroke at rest is 70–90 mL.
The end-diastolic ventricular volume is about 130 mL.
Thus, about 50 mL of blood remains in each ventricle at the end of systole (end-systolic ventricular volume).
Ejection fraction is (index of ventricular function) % end-diastolic ventricular volume (≈65%) ejected per stroke.
Injecting radionuclide-labeled red blood cells to image cardiac blood pool at the end of diastole and systole can be used to calculate the ejection fraction.

117. Events in Early Diastole
After full ventricular contraction, the falling ventricular pressure drop more rapidly: the period of protodiastole, lasting for about 0.04 s.
Prodiastole ends when momentum of blood is overcome and aortic and pulmonary valves close to set up transient vibrations in the blood and vessel walls.
After the closure of the valves, the blood pressure continue to drop rapidly during the period of isovolumetric ventricular relaxation.
Isovolumetric relaxation ends when the ventricular pressure falls below the atria pressure and the AV valves open to permit ventricular filling.

118. Filling is rapid at first, then slows as the next cardiac contraction approaches.
Atrial pressure continue to rise after the end of ventricular systole until the AV valves open, then drops and slowly rises again until the next atrial systole.

119. Contribution of Pericardium During Cardiac Cycle
Pericardium normally separates the heart from the rest of thoracic viscera within the pericardial space.
This pericardial space (of 5-30 mL clear fluid) lubricates the heart, permitting contraction with minimal friction.
Timing within Cardiac Cycle
Although events on the 2 sides are similar, they are asynchronous somewhat in that:
Right atrial systole precedes left atrial systole, and contraction of right ventricle starts after that of the left.

120. As pulmonary arterial pressure is lower than that of aortic, right ventricular ejection begins before that of the left.
During expiration, the pulmonary and aortic valves close at the same time; but during inspiration, the aortic valves closes slightly before pulmonary valves.
The slower closure of the pulmonary valve is due to lower impedance of the pulmonary vascular tree.
When measured over a period of minutes, the left ventricular output is equal to that of right.
Nevertheless, transient differences in output during the respiratory cycle occur in healthy individual.

121. Length of Systole and Diastole
Cardiac muscle contracts and repolarises faster at high HR
The duration of systole can decrease from 0.27 s at HR of 65 to 0.16 s at HR of 200 bpm.
The reduction in systole is due to a decrease in systolic ejection time.
Systolic duration is much more fixed than diastolic: while HR is increased, diastole is shortened to a greater degree.
For example, at a HR of 65, diastolic duration is 0.62 s whereas at the HR of 200 it is 0.14 s.
This observation has important physiologic and clinical implications.

122. During diastole the heart muscle rests and coronary blood flow to the sub-endocardial portions of the left ventricles.
Most of the ventricular filling occurs in diastole.
The filling is accurate at 180 bpm provided there is ample venous return, producing increase in cardiac output (CO).
At a very high rate ventricular filling is compromised to a degree that CO falls and symptoms of heart failure.
The highest ventricular rate possible is 400/min theoretically.
However, AV node does not conduct more than 230 impulses/min, because of the long refractory period

123. Although, a ventricular rate of 230/min is seen only in paroxysmal ventricular tachycardia.
Duration of Events During Isovolumetric Ventricular Contraction
The events observed during the isovolumeric contraction by using ECG, phonocardiogramme, carotid pulse simultaneously are:
Electromechanical systole (QS₂)
Pre-ejection period (PEP)
Left ventricular ejection time (LVET)

124. QS₂ = period from the onset of QRS complex to the closure of aortic valves – 2nd heart sound.
LVET = period from the beginning of carotid pressure rise to the dicrotic notch.
PEP = QS₂ – LVET = period for the electromechanical events that precedes systolic ejection
PEP ratio LVET = 0.35 normally.
It increases without change in QS₂ when left ventricular performance is compromised in cardiac diseases.
Arterial Pulse
The blood pumped into aorta during systole moves the

125. Blood in the aorta forward and set up a wave that travels along the arteries.
This pressure expands the arterial wall as it travels and the expansion is palpable as the pulse.
The pulse wave travels at 4 m/s in aorta, 8 m/s in large arteries, 16 m/s in the small arteries of young adults.
Wave velocity is much higher than blood flow velocity.
The pulse is felt at the wrist about 0.1 s after the peak systolic ejection into the aorta.
The pulse wave moves faster with advancing age, as the arteries become more rigid.

126. Pulse strength is always determined by pulse pressure.
Pulse is weak during shock, but it is strong with large stroke volume during exercise or histamine administration.
Also a very high pulse pressure wave can be felt or heard by the individual (palpitation).
The pulse is particularly strong when the aortic valve is incompetent (aortic insufficiency).
Such that it can produce a force of systolic ejection sufficient to make the head nod with each heartbeat.
Dicrotic notch is a small oscillation on the falling phase of pulse wave.

127. It is caused by vibration of the aortic valves snap shut.
It is visible when the pressure wave is recorded but not palpable.
Pulmonary artery pressure curve also has a dicrotic notch produced by the closure of the pulmonary valves.
Heart Sound
There 4 heart sounds
1st heart sound is a low slightly prolonged “lub” sound.
It is caused by vibration set up by sudden mitral and tricuspid valves closure at the start of ventricular systole.

128. The 1st heart sound, “lub”, has a duration of 0
The 1st heart sound, “lub”, has a duration of 0.15 s and a frequency of Hz.
It is soft when the heart rate is low because:
The ventricles are well filled with blood and
The leaflets of the AV valves float together before systole
The 2nd heart sound is a shorter, high-pitched “dup”.
It is caused by vibrations associated with pulmonary and aortic valves closure just after the end of ventricular systole.

129. The 2nd heart sound lasts about 0.12 s with a frequency of 50 Hz.
It is associated with diastolic phase.
This makes it loud and sharp when DBP in the aorta is elevated, causing the respective valves to shut briskly at the end of systole.
Interval between aortic and pulmonary valve closure during inspiration is long enough for 2nd heart sound to be reduplicated.
This is physiologic splitting of the 2nd heart sound, however, there are also pathophysiologic splitting in various diseases.

130. The 3rd heart sound is a soft low-pitched sound heard about ⅓ the way through diastole in normal young adults.
It is produced by the vibration set up by the inrush of blood during rapid ventricular filling.
It coincides with this period of rapid ventricular filling.
It has a duration of 0.1 s.
The 4th heart sound can be heard sometimes immediately before the 1st heart sound.
It is produced during ventricular filling by high atrial pressure or stiff ventricles in ventricular hypertrophy.

131. Murmurs or Bruits
They are abnormal sound heard in various part of the cardiovascular system.
It is the sound of blood flow at a velocity above critical velocity owing to obstruction in blood flow, becoming turbulent.
There are 4 major murmurs owing to:
Heart valve defects
Vascular obstruction of diseases
Septal defects
Physiological adjustment

132. Heart Valve Defect Murmurs
Murmurs are produced by turbulent flow owing to:
Narrowed valve orifice (stenosis).
Backward flow as in case of incompetent valves (regurgitation or insufficiency).
Murmur of a particular valve is best detected using stethoscope over the particular valve.
Aortic and pulmonic valves murmur at the heart base.
Mitral valve murmur at the heart apex.
Hole in the aortic valve cusp produces a loudest murmur.
It is a high-pitched musical diastolic murmur sometimes audible without stethoscope several feet away from patient.

133. Aortic or pulmonic stenosis murmur is heard during systole.
The character accentuation, and transmission of sound are used to locate its origin in one valve or the other.
Aortic or pulmonic stenosis murmur is heard during systole.
Aortic or pulmonic insufficiency is heard during diastole
Mitral or tricuspid stenosis is heard during diastole
Mitral or tricuspid insufficiency is heard during systole.
Vascular Obstruction Bruits/Murmurs
The following are examples of bruits or murmurs heard outside the heart owing to vascular obstructions.
Bruits heard over a large highly vascular goiter

134. Physiological Adjustment Murmurs
Bruits heard over a carotid artery when its lumen is narrowed and distorted by atherosclerosis
Murmurs heard over aneurysmal dilation of aorta, arteriovenous fistula, patent ductus arteriosus.
Septal Defects
Congenital interventricular septal defects produces systolic murmurs as as blood flow from left to right ventricle.
Interatrial septal defects also can produce soft murmurs.
Physiological Adjustment Murmurs
They are normal systolic murmurs produced in:
Children and adults without cardiovascular diseases.
Anaemic patients owing to low blood viscosity and rapid flow.

135. Echocardiography
Echocardiography is a noninvasive technique that does not involved injections or insertion of catheter to evaluate wall movements and other aspects of cardiac functions like:

137. In echocardiography, pulse of ultrasonic waves at 2
In echocardiography, pulse of ultrasonic waves at 2.25 MHz are emitted from a transducer.
This transducer also functions as a receiver to detect waves reflected back from various portion of the heart.
Reflections occur whenever and wherever acoustic impedance changes.
This produce a recording of the echoes displayed against time on an oscilloscope.
This is a record of the movements of the ventricular wall, septum and valves during the cardiac cycle.
Echocardiography combined with Doppler techniques can measure blood flow velocity and volume through valves.
It has clinical applications in evaluating and planning therapy with patients with valvular lesions