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. Determinants of cardiac function
Neurohormonal
systems
Electrical
activation
Excitation-contraction
Cardiovascular interactions
& loading conditions
Pump function
Contraction
mechanisms
Anatomy & geometry

3. Cardiac mechanics
Contraction mechanisms
Excitation-contraction coupling
Pump function (+ PV loops)

4. Literature
•
•
•
•
Medical Physiology - Boron & Boulpaep
Cardiovascular Physiology Concepts – Klabunde
Heart Disease – Braunwald
Cardiovascular Medicine - Camm

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. Cardiac muscle, coloured TEM

7. Contractile proteins

8. Contractile proteins, transverse section

9. Contractile proteins, transverse section

10. Myofilament interaction (sliding filaments)

11. Crossbridge cycling – power stroke

12. Crossbridge cycling

13. Sarcomere, contraction-relaxation

14. Myosin

15. Thick filament (Myosin)
300-400 myosin molecules, 460kD
Head region, ATP and actin binding sites
Cross-bridges, every 14.3nm, 600 angle

16. Thin filament (Actin)
Actine, globular protein, 44kD, 5.5nm
Tropomyosin
Troponine complex, regulatory

19. Actin-Myosin interaction

20. Myosin, ATP dependent motor proteins

21. Myosin V, movement along an actin filament
Spudich - Nature Reviews Molecular Cell Biology 2001

22. Molecular motors

23. Actin-Myosin & Titin

24. Isotonic contraction:
force development and shortening

25. Isometric contraction:
maximal force development, no shortening

26. Peak isometric force is length-dependent
B
C
D

27. 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

28. 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

29. Isometric and isotonic contractions
AFTERLOAD
PRELOAD

30. Actin – Myosin overlap

31. Sarcomere Force-Length relationship

32. 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