G1BH 2012-2013 - HC-13 en HC-14

Cardiac mechanics

Paul Steendijk, PhD

Associate Professor Cardiovascular Physiology
Dep...
Determinants of cardiac function
Neurohormonal
systems

Electrical
activation

Excitation-contraction

Cardiovascular inte...
Cardiac mechanics
Contraction mechanisms

Excitation-contraction coupling

Pump function (+ PV loops)
Literature
•
•
•
•

Medical Physiology - Boron & Boulpaep
Cardiovascular Physiology Concepts – Klabunde
Heart Disease – Br...
From the sarcomere to the heart
From shortening to ejection
myocardium:
beating heart

myofilaments:
contractile
sarcomere...
Cardiac muscle, coloured TEM
Contractile proteins
Contractile proteins, transverse section
Contractile proteins, transverse section
Myofilament interaction (sliding filaments)
Crossbridge cycling – power stroke
Crossbridge cycling
Sarcomere, contraction-relaxation
Myosin
Thick filament (Myosin)

300-400 myosin molecules, 460kD
Head region, ATP and actin binding sites
Cross-bridges, every 14....
Thin filament (Actin)

Actine, globular protein, 44kD, 5.5nm
Tropomyosin
Troponine complex, regulatory
Actin-Myosin interaction
Myosin, ATP dependent motor proteins
Myosin V, movement along an actin filament

Spudich - Nature Reviews Molecular Cell Biology 2001
Molecular motors
Actin-Myosin & Titin
Isotonic contraction:
force development and shortening
Isometric contraction:
maximal force development, no shortening
Peak isometric force is length-dependent

B

C

D
Force-length relationship
Peak Isometric
Force-Length
relationship

Landesberg et al. Am J Physiol Heart Circ Physiol 1999...
Force-length relationship
Peak Isometric
Force-Length
relationship

Passive
Force-Length
relationship

Landesberg et al. A...
Isometric and isotonic contractions

AFTERLOAD

PRELOAD
Actin – Myosin overlap
Sarcomere Force-Length relationship
Possible mechanisms Frank-Starling Relationship
Starling: “Law of the Heart”
(Linacre Lecture, 1915)
Increased sarcomere l...
G1BH 2012 2013 HC-13-14 - Contractie mechanismen 1 en 2 - steendijk - PDF
G1BH 2012 2013 HC-13-14 - Contractie mechanismen 1 en 2 - steendijk - PDF
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G1BH 2012 2013 HC-13-14 - Contractie mechanismen 1 en 2 - steendijk - PDF

  1. 1. G1BH 2012-2013 - HC-13 en HC-14 Cardiac mechanics Paul Steendijk, PhD Associate Professor Cardiovascular Physiology Department of Cardiology, LUMC p.steendijk@lumc.nl 2013.02.13
  2. 2. Determinants of cardiac function Neurohormonal systems Electrical activation Excitation-contraction Cardiovascular interactions & loading conditions Pump function Contraction mechanisms Anatomy & geometry
  3. 3. Cardiac mechanics Contraction mechanisms Excitation-contraction coupling Pump function (+ PV loops)
  4. 4. Literature • • • • Medical Physiology - Boron & Boulpaep Cardiovascular Physiology Concepts – Klabunde Heart Disease – Braunwald Cardiovascular Medicine - Camm
  5. 5. From the sarcomere to the heart From shortening to ejection myocardium: beating heart myofilaments: contractile sarcomeres: proteins contractile units myofibers myocytes ~10 nm myofibrils ~2 µm 10-8 m ~1-10cm ~20x100 µm 10-6 m 10-4 m 10-2 m
  6. 6. Cardiac muscle, coloured TEM
  7. 7. Contractile proteins
  8. 8. Contractile proteins, transverse section
  9. 9. Contractile proteins, transverse section
  10. 10. Myofilament interaction (sliding filaments)
  11. 11. Crossbridge cycling – power stroke
  12. 12. Crossbridge cycling
  13. 13. Sarcomere, contraction-relaxation
  14. 14. Myosin
  15. 15. Thick filament (Myosin) 300-400 myosin molecules, 460kD Head region, ATP and actin binding sites Cross-bridges, every 14.3nm, 600 angle
  16. 16. Thin filament (Actin) Actine, globular protein, 44kD, 5.5nm Tropomyosin Troponine complex, regulatory
  17. 17. Actin-Myosin interaction
  18. 18. Myosin, ATP dependent motor proteins
  19. 19. Myosin V, movement along an actin filament Spudich - Nature Reviews Molecular Cell Biology 2001
  20. 20. Molecular motors
  21. 21. Actin-Myosin & Titin
  22. 22. Isotonic contraction: force development and shortening
  23. 23. Isometric contraction: maximal force development, no shortening
  24. 24. Peak isometric force is length-dependent B C D
  25. 25. Force-length relationship Peak Isometric Force-Length relationship Landesberg et al. Am J Physiol Heart Circ Physiol 1999;276:H998-H1011 ©1999 by American Physiological Society
  26. 26. Force-length relationship Peak Isometric Force-Length relationship Passive Force-Length relationship Landesberg et al. Am J Physiol Heart Circ Physiol 1999;276:H998-H1011 ©1999 by American Physiological Society
  27. 27. Isometric and isotonic contractions AFTERLOAD PRELOAD
  28. 28. Actin – Myosin overlap
  29. 29. Sarcomere Force-Length relationship
  30. 30. Possible mechanisms Frank-Starling Relationship Starling: “Law of the Heart” (Linacre Lecture, 1915) Increased sarcomere length >>> Increased force of contraction Possible mechanisms: - Optimal actin-myosin overlap - Reduced lattice spacing - Altered myosin head orientation - Increased Ca sensitivity

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