Dr. Adelina Vlad, MD PhD

Associate Professor, Physiology Department

UMPh ,Carol Davila’ Bucharest

Mechanical Properties of the Heart

Myocardial Properties

EXCITABILITY/ bathmotropia

AUTOMATICITY/ chronotropia

CONDUCTIBILITY/ dromotropia

CONTRACTILITY/ inotropia

RELAXATION/ lusitropia

Mechanical Properties of the Heart

Contractility inotropia

Relaxation lusitropia

Mechanical properties of

I. The myocardial fiber

II. The heart as a whole

I. Mechanical Events of the

Myocardial Fiber

Types of Muscles

Muscle Properties

Cardiac Muscle vs Skeletal Muscle

The Myocardial Fiber Striated, structurally similar, but not identical with the skeletal

muscle fiber

Skeletal Muscle

Skeletal Muscle

The Sarcomere

The Sarcomere

Structure of Thin and Thick Filaments

The Role of Ca2+ in Triggering

Contraction

Z line

M band

Structural Proteins of the Sarcomere

Actin Myosin

TitinAnchoring part

Elastic segment

Actin

Myosin

Moderate

stretch

Important stretch

The Cross-Bridge Cycle

Each cycle advances the myosin head by two actin monomers

The Cross-Bridge Cycle

Calcium Transport and Storage

The transverse

tubules (T tubules)

are extensions of

the plasma

membrane,

penetrating the

muscle cell at two

points in each

sarcomere:

the junctions of the A and I bands

The Triad

The Tetrade A tetrad of four L-

type Ca2+

channels on the T tubules faces a single Ca2+-release channel of the SR

Each L-type Ca2+

channel interacts with the foot of one of the four subunits of the Ca2+-release channel

Excitation-Contraction Coupling

Cardiac Contraction Requires Ca2+

Entry Through L-type Ca2+ Channels

EC coupling in skeletal muscle does not require Ca2+ influx

through L-type Ca2+ channels - the linkage between activated L-

type Ca2+ channels (Cav1.2, dihydropyridine receptors) in the T-

tubule membrane and the Ca2+ release channels is mechanical

and does not require Ca2+ entry per se

Cardiac contraction has an absolute requirement for Ca2+ influx

through these channels during the action potential.

The increase in [Ca2+]i resulting from Ca2+ influx alone is not

sufficient to initiate contraction is greatly amplified by Ca2+-

induced Ca2+ release from the SR through the Ca2+-release

channels, because the Ca2+-release channels remain open for a

longer period than do L-type Ca2+ channels

Calcium-Induced Calcium Release

Particularities of the Myocardial

EC-Coupling The initiating event

in the skeletal muscle is the arrival of an action potential at the

neuromuscular junction, the release of acetylcholine, and the

initiation of an end-plate potential.

in the ventricular myocyte, action potentials in adjacent

myocytes depolarize the target cell through gap junctions and

generate an action potential

T tubules

unlike skeletal muscle cells, cardiac myocytes also have axial

T tubules that run parallel to the long axis of the cell and

interconnect adjacent radial T tubules

Particularities of Myocardial EC-

Coupling

Cardiac contraction requires Ca2+ entry through L-type Ca2+

channels

Cardiac myocytes have a very high density of mitochondria and

thus are capable of sustaining very high rates of oxidative

phosphorylation (i.e., ATP synthesis, that fuels the cross-bridge

cycling, as well as the termination of contraction)

E-C Coupling in the Skeletal Muscle

E-C Coupling in the Cardiac Muscle

Ca2+ Removal From the Cytoplasm

After you activate your book, you will get

Termination of Contraction The relaxation of the contractile proteins depends on:

(1) extrusion of Ca2+ into the extracellular fluid

(2) re-uptake of Ca2+ from the cytosol by the SR

(3) dissociation of Ca2+ from troponin C

Termination of Contraction (2) and (3) are highly regulated:

Phospholamban (PLN), an integral SR membrane protein, inhibits

SERCA2a.

Phosphorylation of PLN by any of several kinases relieves

phospholamban's inhibition of SERCA2a, allowing Ca2+

resequestration to accelerate

an increase in the rate of cardiac muscle relaxation (e. g. by β1-

adrenergic agonists)

β1-Adrenergic agonists accelerate relaxation by promoting

phosphorylation of troponin I, which in turn enhances the dissociation of Ca2+ from troponin C.

Phosphorylation of Phospholamban and of Troponin I

Speeds Cardiac Muscle Relaxation

Increasing the Entry of Ca2+ Enhances

the Contractile Force

In skeletal muscle the strength of contractions is regulated by

frequency summation and multiple-fiber summation

In cardiac muscle

frequency summation is precluded the strength of cardiac

muscle contraction is regulated by modulating the

contractile force generated during each individual muscle

twitch

contractile function is regulated by:

modulating the magnitude of the rise in [Ca2+]i

altering the Ca2+ sensitivity of the regulatory proteins

Effects of NE on Contractility

Norepinephrine increase the contractile force of the heart:

acts through the β-type adrenergic receptor

increases the generation of cAMP activates PKA

phosphorylate the L-type Ca2+ channels = increases the

influx of Ca2+ an increase in contractile force.

the cAMP pathway also increases the Ca2+ sensitivity of the

contractile apparatus by phosphorylating one or more of the

regulatory proteins an increase in the force generated for

any given [Ca2+]i.

The Effects of Sympathetic Stimulation

on Contraction and Relaxation

Effects of ACh on Contractility

ACh, acting through muscarinic ACh receptors, raises

intracellular cGMP concentrations

the cGMP-dependent phosphorylation of L-type Ca2+

channels at sites distinct from those phosphorylated by the

cAMP-dependent kinase,

causes a decrease in Ca2+ influx during the cardiac action

potential and thus a decrease in the force of contraction

Cardiac Glycosides (Digitalis)

Digitalis

Antagonists and Agonists of L-type

Ca2+ Channels

After you activate your book, you will get

SKELETAL MUSCLE CARDIAC MUSCLE

Mechanism of

excitation

Neuromuscular transmission Pacemaker potentials.

Electrotonic depolarization

through gap junctions

Electrical activity of

muscle cell

Action potential spikes Action potential plateaus

Ca2+ sensor Troponin Troponin

Excitation-

contraction coupling

L-type Ca2+ channel (DHP receptor)

in T-tubule membrane coupling to

Ca2+-release channel (ryanodine

receptor) in SR

Ca2+ entry through L-type

Ca2+ channel (DHP

receptor) triggers Ca2+-

induced Ca2+ release from

SR

Terminates

contraction

Breakdown of ACh by

Acetylcholinesterase

Action potential

repolarization

Twitch duration 20-200 ms 200-400 ms

Regulation of force Frequency and multifiber

summation

Regulation of calcium entry

Metabolism Oxidative, glycolytic Oxidative

Single Twitch and Tetanus in the

Skeletal Muscle

The Law of Periodic Unexcitability The heart is unexcitable during systole

Muscle Length and Tension

Types of Contraction

II. Mechanical Events of the Whole

Heart

Muscle Layers of the Myocardium

The spiral bundle

contraction wrings the blood

out of the ventricle

The contraction of the apex

before of the bases of the

ventricle propels blood

upward to the Ao and PA

LV

RV

PA

Ao

Tricuspid

Mitral

Geometry of Right Venticular

Contraction

A small movement

of the free wall

ejects a large

volume due to its

large surface area

RV ejects a large

volume at low

pressure

Geometry of Left Venticular

Contraction

The conical shape

of the lumen gives

the LV a smaller

surface-to-volume

ratio than the RV

helps LV to

generate high

pressures

RV

LV

1

2

Comparison of the LV and RV

Contraction

RIGHT VENTRICULAR PRESSURE AND FLOW LEFT VENTRICULAR PRESSURE AND FLOW

RV

LV

Peak systolic:

130 mm Hg

End dyastolic:

10 mm Hg

Peak systolic:

30 mm Hg

End dyastolic:

6 mm Hg

The Cardiac Cycle The sequence of mechanical and electrical events that repeats

with every heartbeat is called the cardiac cycle.

The cardiac cycle consists of a period of relaxation called

diastole, during which the heart fills with blood, followed by a

period of contraction called systole.

The duration of the cardiac cycle is the reciprocal of heart rate:

For a heart rate of 75 beats/min, the cardiac cycle lasts 0.8 s

The Cardiac Cycle

The electrical pacemaker in the sinoatrial node determines the

duration of the cardiac cycle

The electrical properties of the cardiac conduction system and

cardiac myocytes determine the relative duration of contraction

and relaxation

The Closing and Opening of the Cardiac Valves Define

Four Phases of the Cardiac Cycle

Cardiac valves open

passively when upstream

pressure exceeds

downstream pressure.

They close passively when

downstream pressure

exceeds upstream pressure.

Pressure Gradients in the Heart

Cardiac Cycle of the Atria Durig diastole atria opperate as passive reservoirs

Atrial contraction enhances ventricular filling and cardiac

output to a small degree.

For a heart rate of 75 (cycle duration = 0,8 s), atrial systole lasts

0,1 s and atrial diastole, 0,7 s

Cardiac Cycle of The Ventricles The cardiac cycle of the ventricles can be divided in four

phases:

1. Inflow phase (VENTRICULAR FILLING)

2. Isovolumetric contraction

3. Outflow phase (EJECTION)

4. Isovolumetric relaxation

Systole includes phases 2 and 3, and diastole includes phases

4 and 1.

For a heart rate of 75 (cycle duration = 0,8 s), ventricular systole

lasts approximately 0,3 s, and ventricular diastole approximately

0,5 s

1. Inflow phase. The inlet valve is open and the outlet valve is

closed.

RAPID VENTRICULAR FILLING (0,11 s)

DIASTASIS (0,19 s)

ATRIAL CONTRACTION (0,11 s)

2. Isovolumetric contraction (0,05 s). Both valves are closed,

with no blood flow.

3. Outflow phase (EJECTION). The outlet valve is open and

the inlet valve is closed.

RAPID EJECTION: 0,09 s; 70% of the stroke volume

ejected

SLOW EJECTION: 0,13 s; 30% of the SV ejected

4. Isovolumetric relaxation (0,08 s). Both valves are closed,

with no blood flow.

Events of the cardiac cycle

Slight Asynchrony Between Left and

Right Ventricle

IC IR

E

Ventricular VolumesSV – stroke volume = the amount of blood ejected by each

ventricle during one systole = EDV – ESV = 70 ml

EDV – end diastolic volume = the maximal ventricular volume =

the amount of blood present in the ventricle at the end of diastole

= 120 ml

ESV – end systolic volume = the minimal ventricular volume = the

amount of blood present in the ventricle at the end of systole =

50 ml

Ventricular VolumesCO - cardiac output = the flow of blood delivered by the heart in

one minute = heart rate x stroke volume

EF – ejection fraction = the stroke volume normalized to the end

diastolic volume:

EF = SV / EDV,

Should exceed 0.55 in a healthy person.

Pressure Values for the Right and Left Heart

Pressures

(mm Hg)

Pressures

(mm Hg)

Right Atrium Left Atrium

Mean 2 Mean 8

Right Ventricle Left Ventricle

Peak systolic

End diastolic

25

6

Peak systolic

End diastolic

130

10

Pulmonary Artery Aorta

Mean

Peak systolic

End diastolic

15

25

8

Mean

Peak systolic

End diastolic

95

130

80

Pulmonary

capillaries

Systemic capillaries

Mean 10 25

Pressure-Volume Loop

Cardiac Performance Is a generic term referring to how efficiently the ventricles are

carrying out their function as a pump

LEFT HEART

CARDIAC

OUTPUT

Performance = Actual CO/ Optimal CO

INPUT OUTPUT

End Diastolic

Volume

Ejection

Fraction

xStroke

Volume

Heart

Rate

•LV relaxation

•LV compliance

•LA function

•Mitral valve

•Pericardium

•Preload

•Afterload

•Contractility

DIASTOLIC

FUNCTION

SYSTOLIC

FUNCTION

=

PRESSURE

IN PULMONARY

VEINS

x

Systolic Function Expresses the ability of the ventricle to empty

It is determined by

Loading conditions

Preload – the load imposed on the ventricle just before

contraction has started, at the end of the diastole (EDV)

Afterload – the systolic load on the ventricle after it has

started to contract (Ao pressure, or more accurate, Ao

impedance)

Contractility – the intrinsic capacity of the myocard to shorten

independent of extrinsic factors (preload, afterload, heart rate)

Preload and the Frank-Starling Law of

the Heart

The intrinsic ability of the heart to adapt the force of ventricular

contraction (SV) to increasing volumes of inflowing blood

(preload, EDV) is called the Frank – Starling law of the heart.

Within physiologic limits, the heart pumps all the blood that

returns to it by the way of the veins.

The greater the heart muscle is stretched during ventricular

filling by an increased EDV, the greater is the force of

contraction and the greater the stroke volume pumped into the

aorta.

Right atrial dilation following an increased venous return

increases the heart rate as well by mechanical stimulation of the

SAN an increased venous return increases the cardiac output

by rising both SV and HR.

Starling Effect on Pressure-Volume

Loop

Force – Length Relationship An increased stretch of the cardiac muscle causes a stronger

contraction.

Why? In skeletal muscle, increased stretch provides a better

interaction between actin and myosin; the amount of tension

developed corresponds to the degree of overlap between the

actin and the myosin filaments

2 mm

2.2 mm

1.4 - 2 mm

> 2.2 mm

In cardiac muscle, as

the sarcomere length

decreases from 2.4 to 1.8

mm, active tension falls

steeply

Since the sarcomere has

the same length in both

types of muscle, the fall in

tension at lower

sarcomere length cannot

be due to the decrease in

the overlap of actin and

myosin

The greater force (f, red curve) developed at higher sarcomere

length (SL) (2.15 mm versus 1.65 mm) in cardiac muscle is

probably due to a length – induced calcium sensitisation; short

sarcomere length somehow reduces the calcium affinity for

TnC

Ca++ transients (c, green curve) are not significantly affected by

sarcomere length

Pressure – Volume Diagram

Shows the limits of ventricular

stretch and the effects of

stretching on systolic and

diastolic pressures

Systolic pressure curve proves

the Frank-Starling law of the

heart: at increasing loading

volumes the force of contraction

increases

Influence of Increased Contractility on

Performance Curves

A ventricular performance

curve

it is a length – tension diagram

that expresses the functional

ability of the ventricles to

pump blood

plots stroke work (P x V) as an

estimate of tension, against

left atrial pressure, as an

estimate of EDV; can be

obtained on a patient

Positive inotropic agents shift the performance curve upward

and to the left Starling’s law is not a fixed relationship

Afterload and the Anrep Effect A healthy heart can overcome any physiological acute increase

in afterload; after an initial decrease, the SV comes back to

normal whithin a couple of heart beats

How?

The Anrep effect (homeometric autoregulation):

– when Ao pressure increases abruptly, a positive inotropic effect

follows within 1-2 minutes

- mechanism: increased wall tension stimulates stretch receptors

a rise of [Ca++]i

The ”garden-hose” effect:

- increased Ao pressure rises the coronary perfusion; an

increase in the coronary artery pressure is distending the heart

from within its walls (stretch), inducing a better shortening of the

myocardial fibers

Preload is related to the degree to which the myocardial fibers

are stretched at the end of the diastole

Afterload is related to the wall stress generated by the

myocardial fibers during systole

Heart Rate and the Force of Ventricular

Contraction

An increase in heart rate progressively enhances the force of

ventricular contraction (Bowditch staircase or treppe

phenomenon)

Why? – During rapid stimulation more Ca++ enter the cell than

can be handled by the mechanisms for Ca++ exit

Time

Tension

Contractility Contractility is the inherent capacity of the myocardium to

shorten independent of changes in load or heart rate

Increased contractility

Means a greater rate of contraction to reach a higher peak of

force

It is explained at a molecular level by increased interaction

between Ca++ and the contractile proteins

Contractility or inotropism (ino, fiber; tropos, to move) is an

important regulator of the myocardial oxygen uptake

Clinical Assessment of Contractility

Ejection fraction, EDV – ESV / EDV, but depends also on

preload and afterload

The rate of pressure development during ejection, DP/Dt, and

the velocity of ejection; are influenced by preload; they

correlate well with inotropic interventions

Pressure-volume loop

LV pressure

The Rate of Pressure Development

During Ejection

Isoprenaline Effort

Pressure – Volume Loops Are among the best of the current methods for estimating the

contractility of the intact heart

The maximal pressure that can be developed by the ventricle at

the ESV is defined by the end-systolic pressure-volume

relationship (ESPVR), which represents the inotropic state of

the ventricle.

Slope of end-systolic pressure-volume relationship (ESPVR

or Es) – almost insensitive to preload, afterload, and heart rate

most reliable index for assessing myocardial contractility

Inotropic agentsModifiers of contractility can affect the dynamics of cardiac muscle

contraction, independent of preload or afterload

Positive inotropic agents increase [Ca++]i by

- opening Ca++ channels

- inhibiting Na-Ca exchanger

- inhibiting the Ca++ pump, all at the plasma membrane

Examples: Adrenergic agonists

Cardiac glycosides (digitalis derivatives)

High extracellular [Ca++]

Low extracellular [Na+]

Increased heart rate

Influence of Increased Contractility on

Performance Curves

A ventricular performance

curve

it is a length – tension diagram

that expresses the functional

ability of the ventricles to

pump blood

plots stroke work (P x V) as an

estimate of tension, against

left atrial pressure, as an

estimate of EDV; can be

obtained on a patient

Positive inotropic agents shift the performance curve upward

and to the left Starling’s law is not a fixed relationship

Negative inotropic agents decrease [Ca++]i

Examples:

Ca++-channel blockers (verapamil, diltiazem)

Low extracellular [Ca++]

High extracellular [Na+]

Diastolic Function

Expresses the filling capacity of the ventricle

It is influenced by several factors:

o Ventricular relaxation (lusitropia)

o Ventricular compliance

o Atrial function

o AV valve

o Pericardium

o Heart rate

Pressure – Volume Diagram Shows the limits of ventricular

stretch and the effects of

ventricular volumes on systolic

and diastolic pressures

Diastolic pressure curve is an

expression of ventricular

compliance:

C = DV / DP

Assessment of Diastolic Function Izovolumic relaxation

Parameters: duration of izovolumic relaxation (from Ao closure

until Mi opening), time constant of isovolumic pressure decay (t,

ms)

Methods: echocardiography, Doppler echography,

mechanograms

Assessment of Diastolic Function Ventricular filling

Parameter: pressure-volume relationship during ventricular

filling; the slope of the pressure – volume curve dP/dV plotted

from the minimal diastolic pressure to the end-diastolic pressure

represents ventricular stiffness

Methods: Doppler echocardiography

Work of the Heart The stroke work output of the heart is the amount of energy

that the heart converts to work during each heartbeat while

pumping blood into the arteries

The general expression of external work done when a mass is

lifted a certain distance is W = force x distance

For pressure moving a volume, the external work is:

W = P · DV

The pressure-volume area

is used for calculating the net external work

is an index of myocardial O2 uptake

The pressure-volume area requires invasive monitoring for

accurate determination

In clinics the pressure work can be approximated by the

product of stroke volume and peak systolic blood pressure

(SBP):

SBP x SV

Minute work output is the total amount of energy

converted to work in 1 minute:

Minute work = SBP x SV x HR

The total external work is the sum of the pressure-volume work

(= area of the PV loop) and the kinetic energy

W = P · DV + ½ mv2

Kinetic energy

½ mv2, where m is the mass of blood ejected and v is the

velocity of ejection - represents the energy spent for the

acceleration imparted by the heart to the blood during the

cardiac cycle;

accounts for less than 1% of the total external work in healthy

hearts, but increases steeply in aortic stenosis.

Tension Heat Is the potential energy generated by each contraction that is not

converted to external work but maintains active tension

= the energy cost for isometric contraction

the muscle breaks down ATP and the energy ends up as heat

The pressure against which the ventricle must pump (pressure in

the Ao or the PA) is a major determinant of tension heat

Formula: k · T · Dt , where T is the tension of the ventricular wall,

Dt is the time interval that the ventricle maintains this tension,

and k is a proportionality constant

Total Energy Required for Cardiac

Contraction

The total energy transformed in one cardiac cycle is the sum of

the total external work done on the blood and the tension

heat:

E = P · DV + ½ mv2 + k · T · Dt

E is derived mainly from oxidative metabolism of fatty acids,

lactate or glucose the rate of oxygen consumption by the

heart is a measure of E

Mechanical Efficiency of the Heart Or efficiency of work, is the ratio between the external work

performed and the total energy expenditure during systole, W/E

Can be defined also as the relation between the work

performed and the myocardial oxygen uptake

Maximum efficiency of the normal heart is between 20 and 25

per cent; in heart failure, this can decrease to as low as 5 to10

per cent

! Has nothing to do with how effective the ventricle is expelling the

blood, which is expressed by the ejection fraction (EF =

SV/EDV).