MECHANICAL PROPERTIES OF THE
HEART
Sandor Gyorke, Ph.D.
Office: DHLRI 507
Telephone: (614) 292-3969
Learning Objectives
• Compare and contrast cardiac and skeletal muscle cells
in terms of mechanisms of contraction and relaxation,
cross bridging, and ion transport.
• Define the determinants of myocardial oxygen
consumption
• Relate cardiac muscle mechanics to ventricular function
using LaPlace’s Law: define pressure and volume work
• Describe the effects of parasympathetic and sympathetic
stimulation on cardiac muscle cells.
Learning Resources
 Pathophysiology of heart disease. Fifth Edition, Ed. L.S.
Lilly, Lippincott Williams & Wilkins, Baltimore, MD, 2011
(pp. 23-27; 28-43; 217-227)
 D.E. Mohrman & L.J. Heller. Cardiovascular Physiology,
8th edition, McGraw-Hill, New York 2014.
Lecture Topics
•
Cardiac excitation-contraction coupling.
•
Modulation of myocyte calcium handling by
parasympathetic and sympathetic influences.
•
Force-length relationships.
•
Myocardial oxygen consumption.
Introduction
• Heart muscle has many properties in common with skeletal
muscle. Both muscles are striated, and have similar
contractile elements including sarcomeres that contain thick
and thin filaments. The basic principles of muscle structure
and function are covered in the Bone and Muscle block.
• At the same time many important functional and
morphological differences exist between cardiac and skeletal
muscles, including differences in Ca2+ handling, connectivity,
and energetics.
• This eModule will focus on principles underlying the clinically
relevant concepts of myocardial contractility and pressurevolume relationships as well as oxygen consumption.
Excitation-Contraction Coupling in Cardiac
Muscle
Na+-Ca2+ exchange
Na+
Sarcolemma
Ca2+
Ca2+
Na+ channel
Na+
T-tubule
Ca2+
ATP
Troponin-C
Ca2+
Ca2+ channel
Sarcoplasmic
reticulum
Ryanodine
receptor
Sequence of Events in Cardiac ExcitationContraction Coupling
• Action potential (AP) propagates over the surface of the myocyte
and into the myocyte along the T-tubule.
• The AP in the T-tubule opens voltage dependent Ca2+ channels
allowing the entry of Ca2+ from the extracellular fluid into the cell.
• This rise in cytosolic [Ca2+] causes the release of a larger pool of
Ca2+ stored in the sarcoplasmic reticulum (SR) through Ca2+
release channels called ryanodine receptors. This mechanism is
known as Ca2+-induced Ca2+ release.
• The released Ca2+ binds to troponin, which disinhibits actin and
myosin interactions and results in force production.
• Contraction ends when released [Ca2+] is pumped back to the SR
by Ca2+ ATPase
Relation Between Tension and Cytosolic
Calcium Concentration in Cardiac Muscle
Relative force (%)
100%
peak of
enhanced
contraction
Diastole
10
peak of
normal
contraction
-7
[Ca2+]i (molar)
10
-5
•The rise in [Ca2+] in normal
cardiomyocytes during a beat is
only large enough to produce a
fraction of the intrinsically
available tension.
•The strength of contraction can
be increased by increments of
[Ca2+] attained via inotropic
interventions.
Similarities Between Length-Tension and VolumePressure Relationships
100
50
peak
resting
Pressure (mm Hg)
Force (100% maximum)
200
Intraventricular
systolic pressure
Intraventricular
diastolic pressure
100
0
0
60
120
Length (% resting)
180
Peak and resting force produced
by a stimulated and unstimulated,
respectively, cardiac muscle
strip.
0
100
200
Diastolic volume (ml)
The intraventricular systolic
pressure is similar in shape to the
total force development
measured in a muscle strip.
Contractility Positive and Negative
Inotropes
 CONTRACTILITY (or INOTROPIC STATE) is defined as
the strength of contraction at a constant initial muscle
(sarcomere) length
 Inotropic interventions that increase contractility are
called
 POSITIVE INOTROPES (noradrenaline, digoxin)
 Inotropic interventions that decrease contractility are
called
 NEGATIVE INOTROPES (acetylcholine, Ca2+ channel
blockers)
Positive and Negative Inotropic Effects on
the Ventricular Volume-Pressure Curve
Ventricular pressure
norepinephrine
(digoxin)
control
acetylcholine
End-Diastolic volume
(Ca-channel
blockers,
Heart failure)
Molecular Mechanisms of Positive
Inotropic Effects of Norepinephrine
Ca
Channel
Norepinephrine
AC
b -R
Gs
P
ATP
cAMP
PKA
C
Phospholamban
P
SR CaATPase
R C
Myosin
ATP
Ca2+
Sarcoplasmic
reticulum
Molecular Mechanisms of Negative
Inotropic Effects Of Achetylcholine
Ca
Channel
Ach
AC
mAchR
Gi
ATP
cAMP
Mode of Action of Digoxin in Increasing
Intracellular Cystolic Calcium Concentration [Ca2+]
Na+ -Ca2+
exchange
digoxin
(-)
3Na+
3Na+
(-)
2K+
Ca2+
(-)
[Ca2+]
[Na+] raises
Metabolism
• High fatigue resistance due to a large number of mitochondria
(oxidative phosphorylation) and a good blood supply, which
provides nutrients and oxygen.
• Most of energy comes from fatty acids and carbohydrates.
• Only ~1% of energy is derived from anaerobic metabolism
(through lactate production) at basal metabolic rates.
• In ischemic conditions not enough ATP can be produced to
sustain ventricular contractions.
Main Sources of ATP Production in
Cardiac Muscle
ADP + Pi
Lactic acid
ATP
Amino acids
and ketones
Glycogen
(5%)
Glucose
Fatty
acids
Oxygen
Glycolysis
(35%)
(60%)
Oxidative
Phosphorylation
Major Determinants of Myocardial Oxygen
Consumption (MVO2)
Organ
MVO
2
Cardiac State
MVO2
(ml O2/min per 100g)
(ml O2/min per
100g)
Brain
3
Kidney
5
Skin
0.2
Arrested heart
2
Resting heart rate
8
Resting muscle
1
Heavy exercise
70
Contracting muscle
50
Myocardial O2 consumption

Heart rate

Contractility

Wall tension
(T = Pr/2h, T-wall tension, P
intraventricular pressure, r-radius, and
h-wall thickness)
Coronary blood flow.
Vascular tone (adenosine and
nitric oxide, etc)
Mechanical factors
(compression)
Summary
•
•
•
•
The Ca2+ which enters the cardiomyocyte during the action potential triggers Ca2+induced Ca2+ release from the sarcoplasmic reticulum (SR), causing contraction by
sliding of thick and thin filaments.
The force of contraction is modulated by increasing or decreasing the amount of
Ca2+ released from the SR and bound to troponin binding sites. Sympathetic
stimulation, results in phosphorylation of Ca2+ channels and of the SR Ca2+ pump
regulatory protein phospholamban, thereby increasing SR Ca2+ release and
contractility (positive inotropy). Stimulation of the parasympathetic system reduces
contractility by reducing phosphorylation of the same proteins (negative inotropy).
An increase in myocardial fiber length (as occurs with augmented ventricular filling)
increases contractile strength due to a more optimal overlap between the thin and
thick filaments (Frank-Starling relationship).
The heart relies almost entirely on aerobic metabolism for energy production.
Carbohydrates and fatty acids used as energy sources, the energy of which is
converted into ATP by oxidative metabolism in the mitochondria.
Thank you for completing this module
Questions?
sandor.gyorke@osumc.edu