g1bh 2012 2013 hc-13-14 - contractie mechanismen 1 en 2 - steendijk

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

Cardiac mechanics

Paul Steendijk, PhD

Associate Professor Cardiovascular PhysiologyDepartment of Cardiology, LUMC

p.steendijk@lumc.nl

2013.02.13

Contraction mechanisms

Excitation-contraction

Pump function

Electrical activation

Anatomy & geometry

Cardiovascular interactions & loading conditions

Neurohormonal systems

Determinants of cardiac function

Cardiac mechanics

Contraction mechanisms

Excitation-contraction coupling

Pump function (+ PV loops)

Literature

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

myofilaments:contractile proteins

myofibers

myofibrils

myocardium: beating heart

~20x100 µm ~2 µm

~1-10cm

From the sarcomere to the heartFrom shortening to ejection

myocytes

sarcomeres: contractile units

10-6 m

~10 nm

10-8 m 10-4 m 10-2 m

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

300-400 myosin molecules, 460kD

Head region, ATP and actin binding sites

Cross-bridges, every 14.3nm, 600 angle

Thick filament (Myosin)

Actine, globular protein, 44kD, 5.5nm

Tropomyosin

Troponine complex, regulatory

Thin filament (Actin)

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

C

B

D

Peak isometric force is length-dependent

©1999 by American Physiological Society

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

Force-length relationship

Peak Isometric Force-Length relationship

Landesberg et al. Am J Physiol Heart Circ Physiol 1999;276:H998-H1011

Passive Force-Length relationship

Isometric and isotonic contractions

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Actin – Myosin overlap

Sarcomere Force-Length relationship

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