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Paramedic Electrophysiology. Colbeck

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The full set of slides for the 9 electrophysiology lectures presented on paramedicine.com and YouTube.

The full series:
Part 0 - https://youtu.be/gCbHyK6y4Ms
Part 1 - https://youtu.be/IW3J2Y2ty6w
Part 2 - https://youtu.be/5A_lEW1suAM
Part 3 - https://youtu.be/KV3AaXWrNeY
Part 4 - https://youtu.be/M39wMZFd22o
Part 5 - https://youtu.be/qqnL0Fy3e2g
Part 6 - https://youtu.be/UBINkoW6JzM
Part 7 - https://youtu.be/JmAaibgOrLw
Part 8 - https://youtu.be/oY0XVEkfKr4

Published in: Health & Medicine
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Paramedic Electrophysiology. Colbeck

  1. 1. 1. How does the heart generate electricity and make itself contract? 2. How does our body control the rate and strength of those contractions? 3. How can we, as paramedics, affect this process using medications? Paramedic Cardiology Electrophysiology
  2. 2. Part 0 – Cardiac Electrophysiology - 0 Fundamentals • In this lecture we'll be going over some basic biology to get you ready for cardiac electrophysiology. • https://youtu.be/gCbHyK6y4Ms Part 1 – Cardiovascular Electrophysiology 1 - Movement through the membrane • In this lecture we're going to describe how different ions are able to move in and out of the cell. • https://youtu.be/IW3J2Y2ty6w Part 2 – Cardiovascular Electrophysiology 2 - Electrical Flow In The Heart • In this lecture we're going to talk about how a hunk of meat in your chest can generate electricity. • https://youtu.be/5A_lEW1suAM Paramedic Cardiology Electrophysiology
  3. 3. Part 3 - Cardiovascular Electrophysiology 3 - Action Potential of the Myocytes • In this lecture, we're going to go over the pattern of how ions move in and out of the cell in a regular, repeating pattern - called the Action Potential. • https://youtu.be/KV3AaXWrNeY Part 4 - Cardiovascular Electrophysiology 4 - Action Potential of the Pacemaker Cells • In this lecture we're going to describe how 'pacemaker' cells can spontaneously depolarize without anything stimulating them externally. • https://youtu.be/M39wMZFd22o Part 5 - Cardiovascular Electrophysiology 5 - Anatomy and Physiology of Myocytes • In this lecture we describe how cardiac cells physically contract. • https://youtu.be/qqnL0Fy3e2g Paramedic Cardiology Electrophysiology
  4. 4. Part 6 - Cardiovascular Electrophysiology 6 - Excitation Contraction Coupling • In this video we're going to go over how depolarisation initiates contraction of the heart. • https://youtu.be/UBINkoW6JzM Part 7 - Cardiovascular Electrophysiology 7 - ANS Influence on the Heart • In this lecture we cover how our body changes the rate and strength of our heart, going from external stimuli to the actual ionic changes that take place in the myocardial cells. If I yell 'boo!', your heart speeds up. Why? How? • https://youtu.be/JmAaibgOrLw Part 8 - 8 Paramedic Pharmacology – Antidysrhythmics • In this final lecture, we review cardiac antidysrhythmics with a fairly introductory discussion of how they are classified and how they work. • https://youtu.be/oY0XVEkfKr4 Paramedic Cardiology Electrophysiology
  5. 5. Electrophysiology Part 0 Fundamentals Marc Colbeck Paramedic Cardiology
  6. 6. © Marc Colbeck and Paramedicine.com, used by permission of the author. See: https://creativecommons.org/licenses/by-nc-sa/4.0/ Maintaining this note in the file is sufficient attribution of authorship as per the author.
  7. 7. Topics 0. Fundamentals 1. Movement Through the Membrane 2. Electrical Flow in the Heart 3. The Action Potential – Myocytes 4. The Action Potential – Pacemaker cells 5. Anatomy and Physiology of Myocytes 6. Excitation-Contraction Coupling 7. ANS Influence on the Heart 8. Paramedic Pharmacology - Antidysrhythmics
  8. 8. Priming Questions 1. What is an ‘atom’ 2. What is an ‘element’? 3. What is an ‘ion’? 4. How about anions and cations, what are those? 5. What is a cell? 6. Where did cells come from? 7. What are the walls of a cell made out of? 8. What are the major elements that humans are made out of? 9. Why is phosphorous so important to humans? 10. What are the ions that are important in cardiac electrophysiology?
  9. 9. You Should Already Know Atoms • Basic building block – Protons+ and neutrons in nucleus – Electrons- in orbit Element • Substance made entirely of one type of atom (e.g. H2) Ions • An atom or element with a lack or surplus of either protons or electrons – Anions: negative charge – Cations: positive charge
  10. 10. The Elements of Life 99% CHON (by weight) http://bookofresearch.com/images/earth-transparent.png <1% P, as well as some S, Na, Mg, Cl, K, Ca and Fe 10
  11. 11. The Elements of Life http://1.bp.blogspot.com/-mrMWO9w3UvE/TdE67QdLgOI/AAAAAAAAAEY/Bpu6nJpEBgk/s1600/periodic_table_of_elements1.jpg composition (by weight) 11
  12. 12. The Elements of Life - Phosphorus • Highly reactive, usually found as ‘red phosphorus’ • Used in explosives (napalm), poisons and nerve agents • ‘Organophosphates’ are used as fertilizers, but can also (along with the more potent fluorophosphates) be used as neurotoxins. • 13th Element discovered (in 1669) • Distilled from urine (100L ≈ 5mg) (later discovered in bones) • Now mined from rocks Essential to life: • Part of DNA, RNA and ATP (‘phosphorylation) as well as phospholipids http://0.tqn.com/d/chemistry/1/0/Q/4/1/phosphorus_allotropes.jpg 12
  13. 13. The Elements of Life • Phosphorous – binds to 4 oxygen – hydrophilic • Hydrocarbon tails – hydrophobic http://bioweb.wku.edu/courses/biol115/wyatt/biochem/lipid/P-lipid.gif 13
  14. 14. Cell Membranes http://www.freethought-forum.com/images/anatomy2/phospholipid_bilayer.jpg 14
  15. 15. Cell Membranes Liposomes • “Inside/Outside” https://upload.wikimedia.org/wikipedia/commons/0/01/Liposome_scheme-en.svg 15
  16. 16. Cell Contents What’s inside liposomes? http://www.fossilmuseum.net/Paleobiology/Paleobiology_images/seawater.jpg 16
  17. 17. Cell Contents http://1.bp.blogspot.com/-mrMWO9w3UvE/TdE67QdLgOI/AAAAAAAAAEY/Bpu6nJpEBgk/s1600/periodic_table_of_elements1.jpg What’s in sea water? 17
  18. 18. Cell Contents What’s inside single celled organisms? Same stuff ... • Cations – Na+ – K+ – Mg+2 – Ca+2 • Anions – Cl- – HCO3 - (Bicarbonate) – SO4 -2 (Sulphate) http://www.salmonellablog.com/uploads/image/bacteria.jpg 18
  19. 19. Cell Contents Single celled life became multi-cellular life, surrounding each cell with fluid similar to the sea. http://www.pnas.org/content/104/suppl.1/8613/F1.large.jpg 19
  20. 20. Cell Contents Multi-cellular life came on land http://2.bp.blogspot.com/_2ocgSdkueHs/Rh1viEauffI/AAAAAAAAAVk/viHbhiBj2OY/s400/cartoon-drfunmrevolution.gif 20
  21. 21. Cell Contents Cytosol Na+ K + Ca 2+ Cl - Extracelluar Fluid Na+ K + Ca 2+ Cl - 21
  22. 22. Cell Contents – passing through the membrane • Small, non charged particles/molecules can move through the cell membrane easily, (e.g. O2 and CO2, lipids, hormones, anesthetic agents). • Most ions and large molecules (like proteins) or glucose (which is hydrophilic) can’t get through. P P P P P P P P P P 22
  23. 23. Cations 23
  24. 24. Cations 0.6 nm* 0.8 nm* 1.2 nm* *aqueous values (bonded with H2O)24
  25. 25. Electrophysiology Part 1 Movement Through the Membrane Marc Colbeck Paramedic Cardiology
  26. 26. © Marc Colbeck and Paramedicine.com, used by permission of the author. See: https://creativecommons.org/licenses/by-nc-sa/4.0/ Maintaining this note in the file is sufficient attribution of authorship as per the author.
  27. 27. Topics 0. Fundamentals 1. Movement Through the Membrane 2. Electrical Flow in the Heart 3. The Action Potential – Myocytes 4. The Action Potential – Pacemaker cells 5. Anatomy and Physiology of Myocytes 6. Excitation-Contraction Coupling 7. ANS Influence on the Heart 8. Paramedic Pharmacology - Antidysrhythmics
  28. 28. Priming Questions 1. Describe where Na, K and Ca are normally found in the polarised cell. 2. Describe what a voltage gated channel is and what role it plays in depolarisation 3. Describe what a g-coupled protein receptor is and describe how it effects changes in the cell. 4. Describe what a ligand gated channel is and give one example of a ligand. 5. What are the two primary active transport pumps and describe the ions they exchange and what drives the movement of those ions. 6. Referencing the ion exchangers, describe how cellular hypoxia leads to irritable dysrhythmias. 7. What are the two ion exchangers and describe the ions they exchange and what drives the movement of those ions.
  29. 29. Movement Through the Membrane How does stuff get in and out?? electrochemical K+electrochemical electrochemical Ca2+ Na+ 30
  30. 30. Movement Through the Membrane 31
  31. 31. Movement Through the Membrane Voltage Gated Channels (VGCs) “Gating” is the process of opening the channel. A “voltage gated” channel is a channel that opens due to electrical (voltage) stimuli. Time Dependent • Open when ‘gated’ • Stay open ≈ ‘fast/slow’ • Must close to reset (which is also voltage dependent) I = “intensite de courant” INa K Na Ca 32
  32. 32. Movement Through the Membrane Receptor Gated Channels VGCs hormone or neurotransmitter (“ligand”) receptor RGC K Na Ca 33 Examples: • Insulin • Hormones • Steroids • Prostaglandins
  33. 33. Movement Through the Membrane RGCs VGCs G proteins signal the inside of the cell to do other stuff (secondary messenger systems) “G coupled protein receptor” GCPR RGC K Na Ca 34 Examples: • Neurotransmitters • Adrenaline • Narcotics • 1/3 of drugs!
  34. 34. Movement Through the Membrane VGCs Primary Active Transport Pumps 3 Na+ out 2 K+ in ATP ADP Na/K • 1/3 of all ATP use in the body • 1000 pumps per square micrometre GCPR RGCs RGC K Na Ca 35
  35. 35. Movement Through the Membrane VGCs Primary Active Transport Pumps 3 Na+ out 2 K+ in ATP ADP Na/K Ca2+ out ATP ADP Ca/ATPase GCPR RGCs RGC K Na Ca 36
  36. 36. Movement Through the Membrane VGCs Ion Exchangers Rely on the concentration gradient created by the Na/K pump Na/Ca* 3 Na+ in 1 Ca2+ out 1 Na+ in 1 H+ out Na/Proton GCPR RGCs RGC K Na Ca *The Na/Ca exchanger is inhibited by acidosis, causing an intracellular hypercalcemia, increasing irritability in the cell. This is how hypoxia leads to irritable dysrhythmias. 37
  37. 37. Really Important Concept to Understand! Movement Through the Membrane RGCs VGCs Na/Ca Na/Proton 3 Na+ out 2 K+ in ATP ADP Na/K Ca2+ out ATP ADP Ca/ATPase Really Important Concept to Understand! 3 Na+ in 1 Ca2+ out 1 Na+ in 1 H+ out GCPR RGC K Na Ca
  38. 38. Electrophysiology Part 2 Electrical Flow in the Heart Marc Colbeck Paramedic Cardiology
  39. 39. © Marc Colbeck and Paramedicine.com, used by permission of the author. See: https://creativecommons.org/licenses/by-nc-sa/4.0/ Maintaining this note in the file is sufficient attribution of authorship as per the author.
  40. 40. Topics 0. Fundamentals 1. Movement Through the Membrane 2. Electrical Flow in the Heart 3. The Action Potential – Myocytes 4. The Action Potential – Pacemaker cells 5. Anatomy and Physiology of Myocytes 6. Excitation-Contraction Coupling 7. ANS Influence on the Heart (!) 8. Paramedic Pharmacology - Antidysrhythmics
  41. 41. Priming Questions 1. What is electricity? 2. How does the heart create an electrical current? 3. Specifically what are the roles of ions and gap junctions.
  42. 42. cell Sodium (Na+) Potassium (K+) + - There’s more sodium (+) outside, and more potassium (-) inside Electrical Flow in the Heart 44 There are also negatively charged proteins trapped inside the cell.
  43. 43. To make electricity … cell + - Na+ K+ Electricity “The collection of physical effects related to the force and motion of electrically charged particles, typically electrons, through or across matter and space.” http://www.thefreedictionary.com/electricity Electrical Flow in the Heart 45
  44. 44. Electrical Flow in the Heart The exchange takes place in a wave across the cell 46
  45. 45. Electrical Flow in the Heart Gap Junctions allow Na to flow between cells 47
  46. 46. Electrical Flow in the Heart depolarization conduction → at overshoot conduction → at overshoot conduction → at overshoot depolarization 48
  47. 47. Electrical flow Electrical Flow in the Heart - - - - - - - - -+ -+++++++++ 49
  48. 48. Electrical Flow in the Heart Heart cells - - - ----------- -- -- --- - -------- ---------- - ------------ ---------- ---------- -- -------- - - ---------- --------- ++ ++ + + +++ ++ +++++ +++++ ++ + ++++++++ + ++++++ + + + + +++++++ + + ++ ++++++ +++ + +++++ +++ + + +++++ + + ++ + ++++ + ++ ++++ + + + ++ + +++
  49. 49. Electrophysiology Part 3 The Action Potential: Myocytes Marc Colbeck Paramedic Cardiology
  50. 50. © Marc Colbeck and Paramedicine.com, used by permission of the author. See: https://creativecommons.org/licenses/by-nc-sa/4.0/ Maintaining this note in the file is sufficient attribution of authorship as per the author.
  51. 51. Topics 0. Fundamentals 1. Movement Through the Membrane 2. Electrical Flow in the Heart 3. The Action Potential – Myocytes 4. The Action Potential – Pacemaker cells 5. Anatomy and Physiology of Myocytes 6. Excitation-Contraction Coupling 7. ANS Influence on the Heart 8. Paramedic Pharmacology - Antidysrhythmics
  52. 52. Priming Questions 1. What is meant by ‘resting membrane potential’? 2. Label this diagram appropriately, using the given terms. 1. Polarised 2. Hyperpolarised 3. Depolarisation 4. Repolarisation 3. Also label the phases using the numbers 0-4. 4. Describe in details the movement of ions in phase 0-4 of the depolarisation. 5. What is a ‘potassium rectifier channel’?
  53. 53. The Action Potential - Myocytes 56 0 RMP: Resting Membrane Potential The charge of the inside of the cell compared to the outside. Voltage(mV) - 90 + 20 Polarised Equal internal and external charges Hyperpolarised
  54. 54. The Action Potential - Myocytes VGCs K Na Ca 57 Neuron Myocyte - 90 + 20
  55. 55. The Action Potential - Myocytes Polarised Depolarisation Hyperpolarised Plateau Voltage(mV) - 90 + 20 Polarised 58
  56. 56. The Action Potential - Myocytes 59 Voltage(mV) - 90 + 20
  57. 57. Voltage(mV) - 90 + 20 PHASE 0 • rapid influx of Na through some Na channels • Once an area of the cell wall reaches about 10-20mV less negative than the resting membrane potential (RMP) all the local voltage-gated Na channels open. • Sodium ions rapidly diffuse inward through the Na channels, and depolarisation occurs. • Sodium channels open at about -70 mV, close at about +20 mV • They won’t open again until the RMP falls under about -65 mV again (they have to ‘reset’) Extracellular Intracellular Phase 0 Na+ membrane
  58. 58. Voltage(mV) - 90 + 20 PHASE 1 • Voltage-gated Na channels close • Na influx stops • “Fast” K channels open • A very brief K efflux begins (causing a brief decrease in the RMP) Phase 0 Phase 1 Na+ K+ Extracellular Intracellular membrane
  59. 59. Voltage(mV) - 90 + 20 PHASE 2 • Ca influx begins at -60 to -50 mV through Ca channels • The efflux of K is slowed (small arrow) so an equilibrium is maintained • There’s no sodium movement Phase 0 Phase 1 Phase 2 Na+ K+ Ca++ K+ Extracellular Intracellular membrane
  60. 60. Voltage(mV) - 90 + 20 PHASE 3 • Ca Channels close • An efflux of K from K continues • The Na and Ca channels reset Phase 0 Phase 1 Phase 3Phase 2 Na+ K+ Ca++ Intracellular membrane Extracellular K+K+
  61. 61. Voltage(mV) - 90 + 20 Phase 4 • The cell returns to -80/-90 mV • The K rectifier channel keeps the transmembrane potential stable at -90 mV • The ATP pump restores K into the cell and Na out of the cell • Ca/ATP pump restores Ca to outside the cell • Na/Ca exchanger restores Na and Ca • Na/H exchanger removes H from cells Phase 0 Phase 1 Phase 3Phase 2 Na+ K+ Ca++ Phase 4 Intracellular membrane Extracellular K+K+ K+
  62. 62. Voltage(mV) - 90 + 20 Really Important Concept to Understand! Phase 0 Phase 1 Phase 3Phase 2 Na+ K+ K+ Ca++ K+ K+ Phase 4 Intracellular membrane Extracellular
  63. 63. The Action Potential - Myocytes https://www.youtube.com/watch?v=tLt3ZTeVzEY
  64. 64. https://www.khanacademy.org/science/health-and-medicine/circulatory-system
  65. 65. Electrophysiology Part 4 The Action Potential: Pacemaker Cells Marc Colbeck Paramedic Cardiology
  66. 66. © Marc Colbeck and Paramedicine.com, used by permission of the author. See: https://creativecommons.org/licenses/by-nc-sa/4.0/ Maintaining this note in the file is sufficient attribution of authorship as per the author.
  67. 67. Topics 0. Fundamentals 1. Movement Through the Membrane 2. Electrical Flow in the Heart 3. The Action Potential – Myocytes 4. The Action Potential – Pacemaker cells 5. Anatomy and Physiology of Myocytes 6. Excitation-Contraction Coupling 7. ANS Influence on the Heart 8. Paramedic Pharmacology - Antidysrhythmics
  68. 68. Priming Questions 1. How can SA and AV node cells depolarize without being externally stimulated? 2. What are ‘funny channels’? 3. What ions flow through the funny channels? 4. Why does a pacemaker cell only have phase 4, 0, and 3? 5. Compare the action potential of a pacemaker myocyte versus and ventricular myocyte.
  69. 69. The Action Potential – Pacemaker Cells Different tissue in the heart depolarizes in different ways. The SA and AV nodes are different than the rest of the heart. They are the pacemakers or ‘auto-rhythmic’ cells. 73
  70. 70. The Action Potential – Pacemaker Cells RMP • Spontaneous phase 4 rise (pacemaker potential) • Due to “Funny Channels” (IF) and Ca(T) channels • IF = nonspecific cation channels permeable to both Na+ (influx) and K+ (efflux): • At –ve membrane potential Na influx > K efflux → gradual depolarization • AP in SA and AV nodal cells is similar, but pacemaker potential in SA cells reaches threshold more rapidly Pacemaker Potential Action Potential Na+ influx Ca2+ influx -40 Resting membrane potential •Spontaneous phase 4 rise (pacemaker potential) •Due to “Funny Channels” (IF) and Ca(T) channels • IF = nonspecific cation channels permeable to both Na+ (influx) and K+ (efflux): • At –ve membrane potential Na + Ca influx > K efflux → gradual depolarization • AP in SA and AV nodal cells is similar – but pacemaker potential in SA cells reaches threshold more rapidly 4 0 3
  71. 71. Na/Ca Na/Proton 3 Na+ out 2 K+ in ATP ADP Na/K Ca2+ out ATP ADP Ca/ATPase Really Important Concept to Understand! If Funny Channels (pacemaker cells only) 3 Na+ in 1 Ca2+ out 1 Na+ out 1 H+ in GCPR RGC K Na Ca No fast Na channels in pacemaker cells! Na+ K+ The Action Potential – Pacemaker Cells 75 Na
  72. 72. PHASE 4 • If type channels gradually close as membrane potential becomes more +ve • Membrane potential threshold @ - 40mV, results in spontaneous AP PHASE 0 • Depolarization phase caused by opening of L-type Ca2+ channels (rather than Na+ in contractile cells) • Ca2+ channels slower than Na+ • No fast Na channels = no Phase 1 • Rapid deactivation of Ca channels = no Phase 2 The Action Potential – Pacemaker Cells 4 0 3 4 - 40 (IF) Ca(T) http://rezidentiat.3x.ro/eng/tulbritmeng.files/image001.gif
  73. 73. Pacemaker Potential Action Potential K+ effluxCa2+ influx - 40mV PHASE 3 • Repolarisation occurs when Ca2+ channels close and slow K+ channels open leading to K+ efflux • Return to –ve potential activates pacemaker mechanism Polarized State • Closure of “slow” K+ channels (opened during repolarisation of previous AP) • Cyclic/rhythmic excitation of the cells = “autorhythmicity” The Action Potential – Pacemaker Cells Cell has to hyperpolarize in order for F channels to open again. Cellular hypoxia obstructs this and so leads to bradycardia.
  74. 74. The Action Potential ‘Normal’ Myocytes Pacemaker Myocytes Membrane Potential Stable at – 90 mV Unstable pacemaker potential; usually starts at – 60 mV Events leading to threshold potential Depolarization enters via gap junctions Net Na entry through If channels, reinforced by CaT entry Rise phase of action potential Na entry Ca entry Repolarization phase Extended plateau caused by Ca entry; rapid phase casued by K efflux Rapid; caused by K efflux Hyperpolarization None; resting potential is – 90 mV, the equilibrium potential for K Normally none; when repolarization hits -60 mV the If channels open again. Duration of action potential Extended: 200+ msec Variable: generally 150+ msec Refractory period Long because resetting of Na channel gates delayed until end of action potential None 78
  75. 75. Putting it All Together Comparison of Action Potential’s across the heart Top Bottom Marieb Fig 18-14
  76. 76. Electrophysiology Part 5 Anatomy & Physiology of Myocytes Marc Colbeck Paramedic Cardiology
  77. 77. © Marc Colbeck and Paramedicine.com, used by permission of the author. See: https://creativecommons.org/licenses/by-nc-sa/4.0/ Maintaining this note in the file is sufficient attribution of authorship as per the author.
  78. 78. Topics 0. Fundamentals 1. Movement Through the Membrane 2. Electrical Flow in the Heart 3. The Action Potential – Myocytes 4. The Action Potential – Pacemaker cells 5. Anatomy and Physiology of Myocytes 6. Excitation-Contraction Coupling 7. ANS Influence on the Heart 8. Paramedic Pharmacology - Antidysrhythmics
  79. 79. Priming Questions 1. What percent of myocytes are contractile and what percent are pacemaker cells? 2. What are the two structures of the intercalated disks? Describe their function? 3. What is meant by the term ‘functional syncytium’? 4. What are the two main filaments involved in muscular contraction (which are attached to the M and Z structures) 5. What is tropomyosin? What is its role in contraction? Describe this by explaining the roles of three elements of the troponin complex, Ca and ATP.
  80. 80. Myocytes
  81. 81. Myocytes
  82. 82. Myocytes • ≈99% of cardiomyocytes are contractile • ≈1% specialised autorhythmic (pacemaker) cells
  83. 83. Myocytes
  84. 84. Myocytes
  85. 85. Myocytes Z disks: Z stands for “zwischen” which means “between” in German M line: M stands for “Mittle” which means “middle” in German A bands: A stand for “anisotropic” I bands: I stands for “isotropic”, both A & I have to do with how the structures interact with polarized light H zone: H stands for “helle” which means “bright” in German
  86. 86. Myocytes
  87. 87. Myocytes
  88. 88. Myocytes
  89. 89. Myocytes Troponin C • has a strong affinity for Calcium, when bound it moves the tropomyosin strand off the actin so that the actin can interact with the myosin Troponin I • Inactivates the actin/myosing binding • Defibrillation and (brief) CPR don’t elevate TnI levels • TnI is more specific to cardiac muscle, so is theoretically better to test for Tropinin T • Ties the TnC and TnI together • TnT is analyzed in the ER to determine the presence of A.M.I. • Current research into ‘high sensitivity TnT’ lab tests are being conducted
  90. 90. Myocytes Free Ca ions binding to the actin TnC sites (thus revealing the tropomyosin) plus ATP to myosin S1 heads produces the power stroke.
  91. 91. Myocytes No ATP→ cell unable to dissociate actin and myosin filaments Relaxation of the power stroke (by decoupling the actin and myosin) also requires ATP-supplied energy. This is relevant to APO – any idea how?
  92. 92. Myocytes An animated movie (very short) of the power stroke http://www.sci.sdsu.edu/movies/actin_myosin.html
  93. 93. Electrophysiology Part 6 Excitation-Contraction Coupling Marc Colbeck Paramedic Cardiology
  94. 94. © Marc Colbeck and Paramedicine.com, used by permission of the author. See: https://creativecommons.org/licenses/by-nc-sa/4.0/ Maintaining this note in the file is sufficient attribution of authorship as per the author.
  95. 95. Topics 0. Fundamentals 1. Movement Through the Membrane 2. Electrical Flow in the Heart 3. The Action Potential – Myocytes 4. The Action Potential – Pacemaker cells 5. Anatomy and Physiology of Myocytes 6. Excitation-Contraction Coupling 7. ANS Influence on the Heart 8. Paramedic Pharmacology - Antidysrhythmics
  96. 96. Priming Questions 1. What are the ten stages of excitation contraction coupling? 2. Which ion is the ‘driver’ of contraction? 3. Label the diagram on the following slide
  97. 97. Excitation-Contraction Coupling How do we go from depoloarizing conductive tissue (for example, purkinje fibres) to getting the actin and myosin in a myocyte to contract ??? This process is called “excitation-contraction coupling”.
  98. 98. Excitation-Contraction Coupling The 3 ways a myocyte is usually depolarized 1. Stimulation by a pacemaker cell (in a node). 2. From an adjacent myocyte, injecting sodium through the gap junction. 3. From an adjacent Purkinje fibre injecting sodium through the gap junction.
  99. 99. Excitation-Contraction Coupling How does getting the membrane of a myocyte to depolarize cause the actin and the myosin on the inside to contract?
  100. 100. Excitation-Contraction Coupling 1. An action potential enters from adjacent cell, depolarizing the plasma membrane. This wave of depolarization continues deep into the myocyte via the T- tubules.
  101. 101. Excitation-Contraction Coupling 2. Voltage gated L- type Ca channels open, and Ca enters the myocyte through the plasma membrane Verapamil (isoptin) partially blocks this entry - acting as a negative inotrope.
  102. 102. Excitation-Contraction Coupling 3. Ca binds to a receptor in the sarcoplasmic reticulum. This induces Ca release from the cisternae of the SR. This is called Calcium Induced Calcium Release (CICR). “Nice-to-know” (not tested): These receptors are called “Ryanodine receptors” because we found (experimentally) that the drug Ryanodine will bind to them. “Nice-to-know” (not tested): These receptors are called “Dihydropiridine receptors” because we found (experimentally) that the drug Dihydropiridine will bind to them.
  103. 103. Excitation-Contraction Coupling 4. The local release of Ca causes Ca ‘sparks’ (short lived, highly local releases of Ca throughout the cell)
  104. 104. Excitation-Contraction Coupling 5. Summated Ca sparks create a Ca signal which travels to the actin and myosin.
  105. 105. Excitation-Contraction Coupling 6. Ca binds to Troponin C (TnC) to move the tropomyosin sheath off the actin, with power from ATP, the myosin heads initiate the ‘power stroke’ and contraction occurs.
  106. 106. Excitation-Contraction Coupling 7. Relaxation of the actin/myosin complex occurs when Troponin I (TnI) initiates Ca release from the TnC, and the myosin heads reset to their starting position.
  107. 107. Excitation-Contraction Coupling 8. Ca is pumped back into the SR for storage.
  108. 108. Excitation-Contraction Coupling 9. Calcium in the cytosol is moved out of the cell by the Na/Ca exchanger.
  109. 109. Excitation-Contraction Coupling 10. The Na brought into the cell by the Na/CA exchanger is removed by Na/K- ATPase pump.
  110. 110. Excitation-Contraction Coupling Ca2+ entry in the cell is the driver of contraction
  111. 111. Electrophysiology Part 7 ANS Influence on The Heart Marc Colbeck Paramedic Cardiology
  112. 112. © Marc Colbeck and Paramedicine.com, used by permission of the author. See: https://creativecommons.org/licenses/by-nc-sa/4.0/ Maintaining this note in the file is sufficient attribution of authorship as per the author.
  113. 113. Topics 0. Fundamentals 1. Movement Through the Membrane 2. Electrical Flow in the Heart 3. The Action Potential – Myocytes 4. The Action Potential – Pacemaker cells 5. Anatomy and Physiology of Myocytes 6. Excitation-Contraction Coupling 7. ANS Influence on the Heart 8. Paramedic Pharmacology - Antidysrhythmics
  114. 114. Priming Questions 1. Sketch the layout of the nervous system using the following terms: 1. Central and peripheral 2. Afferent and Efferent 3. Somatic and Autonomic 4. Sympathetic and Parasympathetic 2. Define the following terms. State the role of the SNS and the PSNS on each. 1. Inotropy 2. Chronotropy 3. Dromotropy 4. Irritability 3. Differentiate between the autonomic innervation of the atria and the ventricles. 4. List 5 important categories of factors that determine the autonomic tone in the body. 5. Sketch and label the transmission of signals from the brain to the heart through the nervous system. Include the receptors found on the myocytes for both SNS and PSNS signals. 6. Section Review – label the following diagram
  115. 115. ANS Influence Peripheral Nervous System Central Nervous System Afferent Nervous System Efferent Nervous System Autonomic Nervous System Somatic Nervous System Sympathetic Nervous System Parasympathetic Nervous System The SNS and PSNS balance each other S ensory is … A fferent M otor is … E fferent (SAME)
  116. 116. ANS Influence Most involuntary organs and glands have both sympathetic and parasympathetic innervation. The SNS and PSNS act antagonistically to maintain or quickly restore homeostasis. The sympathetic nervous system excites the receptors (‘fight or flight’ response). The parasympathetic nervous system relaxes the receptors (‘rest and digest’ response).
  117. 117. ANS Influence If you’re a bit vague on the ANS there’s a lecture on it here: https://www.youtube.com/watch?v=7lVt0ABcnM4
  118. 118. ANS Influence Sympathetic Stimulation (thoraco-lumbar) SNS innervates both atria and ventricles ↑ heart rate (↑ chronotropy) ↑ conduction velocity (↑ dromotropy) ↑ strength of contraction (↑ inotropy) ↑ irritability
  119. 119. ANS Influence Parasympathetic Stimulation (cranio-saccral) PSNS innervates only the atria ↓ heart rate (↓ chronotropy) ↓ conduction velocity (↓ dromotropy) ↓ strength of contraction (↓ inotropy) ↓ irritability
  120. 120. The sympathetic branch influences both the atria (i.e. SA Node, the Intraatraial and internodal pathways, and the AV junction) and the ventricles. The parasympathetic branch influences only the atria. parasympathetic sympathetic ANS Influence
  121. 121. TheAutonomicNervousSystem This is important! The SNS can speed up the whole heart, but the PSNS can only slow down the atria. If the ventricles are going too fast, it’s no use trying to activate the PSNS to try and slow them down. The PSNS has no effect on the ventricles.
  122. 122. ANS Influence Contractile cells of the: 1. atrial myocardium 2. ventricular myocardium AV Node cells: 3. velocity of conduction 4. length of refractoriness Automaticity cells of the: 5. SA node 6. AV node 7. atria 8. ventricular conduction system (not velocity, just automaticity) SNS Stimulates PSNS Inhibits Really Important Concept to Understand!
  123. 123. ANS Influence What controls the autonomic balance? 1. Nervous Regulation • cortex and hypothalamus 2. Circulatory Regulation • venous and arterial 3. Respiratory Regulation • inspiration and expiration 4. Other Somatic Regulation • muscles, pain, temp., etc. 5. Chemical Regulation • O2, CO2 , H+ • Adrenaline, Noradrenaline, Thyroxin & Histamine • Poisons and Drugs
  124. 124. ANS Influence What controls the autonomic balance? Thoughts Feelings Hypothalamus Blood pressure Respiration Movement Pain Temperature pH Hormones Chemicals Brain MedullaOblongata Cardiac Acceleratory Centre Cardiac Inhibitory Centre Really Important Concept to Understand!
  125. 125. ANS Influence How does the brain send messages to the heart? MedullaOblongata CIC&CAC Preganglionic neuron R. & L. Vagus Nerve Sympathetic Chain Ganglia Cardiac Plexus Postganglionic nerve Postganglionic nerve HEART
  126. 126. ANS Influence SNS Ganglia Chain Cardiac Plexus
  127. 127. ANS Influence How does the ANS affect the heart? http://www.thecolor.com/images/Magician.gif “...and then the rabbit makes the heart speed up ...”
  128. 128. ANS Influence Let’s connect this ... With this ... HOW IT DOES IT WHAT IT DOES
  129. 129. ANS InfluenceMedullaOblongata CIC&CAC Preganglionic neuron R. & L. Vagus Nerve Sympathetic Chain Ganglia Cardiac Ganglia Postganglionic nerve Postganglionic nerve NAd Ach M2 Ach Really Important Concept to Understand! β1NAd M2Ach
  130. 130. Na/K ATP ADP Ca2+ ATP ADP Ca/Na Na/H GCPR RGC K Ca Clinical Effects of SNS Activation: 1. ↑ Chronotropy: The pumps and exchangers work more quickly, allowing the heart to ‘reset’ more quickly, allowing an increased HR, and an increased resistance to acidosis. 2. ↑ Dromotropy: Ion channels work more quickly, increasing the speed of depolorization. 3. ↑ Inotropy: The increased amount of calcium entering the cell causes an increased release of calcium from the sarcoplasmic reticulum, causing more actin and myosin to bridge, increasing the strength of contraction. β1NAd Na ANS Influence ① ② ③ Really Important Concept to Understand!
  131. 131. ATP ADP ATP ADP GCPR RGC K Ca K+ IKAch M2Ach Na/K Ca2+ Ca/Na Na/H 2-5x more M2 in the atria than in the ventricles Clinical Effects of PSNS activation: 1. ↓ Chronotropy: The pumps and exchangers work more slowly, causing the heart to ‘reset’ more slowly, causing a decreased HR, and an decreased resistance to acidosis. 2. ↓ Dromotropy: Ion channels work more slowly, decreasing the speed of depolorization. 3. ↓ Inotropy: The decreased amount of calcium entering the cell causes a decreased release of calcium from the sarcoplasmic reticulum, causing less actin and myosin to bridge, decreasing the strength of contraction. Na ANS Influence ① ② ③ Really Important Concept to Understand!
  132. 132. Under ischemia or cardiac stress ATP (Adenosine Triphosphate) is degraded down to just Adenosine (Ado) by losing all 3 of its Pi. Adenosine (Ado) P P P Adenosine (Ado) ANS Influence
  133. 133. Ado inhibits NAd release from the SNS postganglionic nerve terminal. Ado inhibits the β1 secondary messenger systems and so acts as a sympatholytic. Ado ↑K efflux and ↓Ca influx, hyperpolarizing (mostly) the AVN, slowing and/or temporarily inactivating it (up to 30s!). It’s kind of like an internal, cardioprotective “emergency brake”. In effect, it works like the PSNS without having to invoke the PSNS. Possibly the nociceptive (pain) pathway for angina. ATP ADP ATP ADP GCPR RGC K If Na+ K+ K+ IKAch Na/K Ca2+ Ca/Na Na/H Na β1 Ca NAd ANS Influence Really Important Concept to Understand!
  134. 134. Quick Review • The SNS speeds things up by affecting various structures in the plasma membrane. • The PSNS slows things down by affecting various structures in the plasma membrane. • Adenosine kind of does a lot of what the PSNS does, without having to stimulate the PSNS. Really Important Concept to Understand! ANS Influence
  135. 135. ATP ADP ATP ADP GCPR RGC K Na/K Ca2+ Ca/Na Na/H Na β1 Ca NAd Ach M2 MedullaOblongata CIC&CAC Preganglionic neuron R. & L. Vagus Nerve Sympathetic Chain Ganglia Cardiac Plexus Postganglionic nerve Postganglionic nerve ANS Influence - Overview M2 Really Important Concept to Understand!
  136. 136. ATP ADP ATP ADP GCPR RGC K If Na+ K+ Na/K Ca2+ Ca/Na Na/H Na β1 Ca NAd Ach M2 MedullaOblongata CIC&CAC Preganglionic neuron R. & L. Vagus Nerve Sympathetic Chain Ganglia Cardiac Plexus Postganglionic nerve Postganglionic nerve ANS Influence - Overview M2 Summary of the ANS Influence in One Diagram
  137. 137. Electrophysiology Part 8 Antidysrhythmic Pharmacology Marc Colbeck Paramedic Cardiology
  138. 138. © Marc Colbeck and Paramedicine.com, used by permission of the author. See: https://creativecommons.org/licenses/by-nc-sa/4.0/ Maintaining this note in the file is sufficient attribution of authorship as per the author.
  139. 139. Topics 0. Fundamentals 1. Movement Through the Membrane 2. Electrical Flow in the Heart 3. The Action Potential – Myocytes 4. The Action Potential – Pacemaker cells 5. Anatomy and Physiology of Myocytes 6. Excitation-Contraction Coupling 7. ANS Influence on the Heart 8. Paramedic Pharmacology - Antidysrhythmics
  140. 140. Priming Questions 1. Explain the Singh/Vaughan classifications of drugs acting on the heart and indicate where on the graph they act. a. Class 1: b. Class 2: c. Class 3: d. Class 4 e. Class 5: 2. Explain the actions of the following antidysrhythmic medications • Adenosine • Amiodarone • Beta Blockers • Calcium Channel Blockers • Digoxin • Magnesium Sulphate • Xylocaine/Lidocaine 3. Why might ‘The Sicilian Gambit’ be a better method to describe ventricular antidysrhythmics?
  141. 141. Antidysrhythmics • Singh / Vaughan Williams classification • “Sicilian Gambit” classification
  142. 142. Antidysrhythmics Singh / Vaughan Williams classification Introduced in 1970 by doctoral candidate at Oxford University, Dr. Bramah Singh (a cardiologist) (his supervisor was EM Vaughan Williams)
  143. 143. Antidysrhythmics – Singh/Vaughan Williams Na/K pump Na/Ca exchanger Na influx through gap junctions Fast K channel efflux T and L channel Ca influx Voltage(mV) - 90 + 10 Ca influx stops K efflux through “slow K” channels Class II Beta Blockers (↓ SNS tone) Class I (a,b,c) Fast Na channel blockers Class III Block K efflux Class IV Block Ca Channels Class V Does other stuff
  144. 144. Class I agents: Sodium Channel Blockers are divided into three groups based upon their effect on the length of the action potential. • Ia lengthens the action potential (right shift) Procainamide • Ib shortens the action potential (left shift) Xylocaine • Ic does not significantly affect the action potential (no shift) Propafenone Antidysrhythmics – Class I http://en.wikipedia.org/wiki/Antiarrhythmic_agent
  145. 145. Antidysrhythmics – Class I http://en.wikipedia.org/wiki/Antiarrhythmic_agent Class Ia Disopyramide, Quinidine, Procainamide Double Quarter Pounder Class Ib Lidocaine, Mexiletine, Tocainide Lettuce, Mayo*, Tomato Class Ic Moricizine, Flecainide, Propafenone More* Fries Please. *note there are two "M"s in the mnemonic, but morcizine and more can clarify which is which) How to remember the Class 1 drugs.
  146. 146. Class II agents are conventional beta blockers. They act by blocking the effects of catecholamines at the β1- adrenergic receptors, thereby decreasing sympathetic activity on the heart. They decrease conduction through the AV node. Antidysrhythmics – Class II http://en.wikipedia.org/wiki/Antiarrhythmic_agent Cardioselective Acebutolol Atenolol Esmolol Metoprolol Non -Cardioselective Aprenolol Labetalol Propranolol Sotalol
  147. 147. Class III agents predominantly block the potassium channels, thereby prolonging repolarization. Since these agents do not affect the sodium channel, conduction velocity is not decreased. Antidysrhythmics – Class III http://en.wikipedia.org/wiki/Antiarrhythmic_agent Amiodarone
  148. 148. Class IV agents are slow calcium channel blockers. They decrease conduction through the AV node, and shorten phase two (the plateau) of the cardiac action potential. They thus reduce the contractility of the heart. However, in contrast to beta blockers, they allow the body to retain adrenergic control of heart rate and contractility. Antidysrhythmics – Class IV http://en.wikipedia.org/wiki/Antiarrhythmic_agent Diltiazem Verapamil
  149. 149. Class V agents Since the development of the original Vaughan-Williams classification system, additional agents have been used that don't fit cleanly into categories I through IV. Some sources use the term "Class V". However, they are more frequently identified by their precise mechanism. Agents include: • Digoxin, which decreases conduction of electrical impulses through the AV node (by inhibiting the Na/K pump) and increases vagal activity via its central action on the central nervous system. • Adenosine, which helps block signals through the AV node • Magnesium sulfate, which helps block ventricular dysrhythmias Antidysrhythmics – Class V http://en.wikipedia.org/wiki/Antiarrhythmic_agent
  150. 150. Antidysrhythmics – The Sicilian Gambit Classification by site of action https://academic.oup.com/eurheartj/article-abstract/12/10/1112/440813
  151. 151. Antidysrhythmics – The Sicilian Gambit Classification by site of action Drugs are classified by the… • voltage gated channels, • receptor gated channels, • pumps • or exchangers … that they affect, and how they affect them.
  152. 152. Adenosine - V Amiodarone - III Diltiazem - IV Labetalol - II Magnesium Sulphate - V Metoprolol - II Nifedipine - IV (Oxygen) (Phenytoin - I) Verapamil - IV Australasian Paramedic Antidysrhythmics
  153. 153. Topics 0. Fundamentals 1. Movement Through the Membrane 2. Electrical Flow in the Heart 3. The Action Potential – Myocytes 4. The Action Potential – Pacemaker cells 5. Anatomy and Physiology of Myocytes 6. Excitation-Contraction Coupling 7. ANS Influence on the Heart 8. Paramedic Pharmacology - Antidysrhythmics

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