Michel Nasser, MD, FAHA

SYSTOLIC PROPERTIES OF THE LEFT VENTRICLE

THE SYSTOLIC PROPERTIES OF THE LEFT VENTRICLE (LV) ARE

THOSE PROPERTIES CONCERNED WITH PARAMETERS OF
MYOCARDIAL PERFORMANCE. MYOCARDIAL PERFORMANCE IS
DEFINED AS THE STATE OF FUNCTION OF THE VENTRICLE (STROKE
VOLUME) FROM A SET OF GIVEN LOADING CONDITIONS AND
CONTRACTILITY. PERFORMANCE OF THE VENTRICLE MAY CHANGE
IF THE LOADING CONDITIONS ARE ALTERED BUT ONLY A CHANGE IN
PERFORMANCE WITHOUT A CHANGE IN LOADING CONDITIONS IS
DEFINED AS AN INDICATION OF A CHANGE IN LV CONTRACTILITY.

I THE FRANK-STARLING RELATIONSHIP

The Length-tension Diagram represents developed tension (isometric) for a

given muscle length or preload. As muscle length is increased, developed
tension increases up to a maximum level of tension at which point, if muscle
length is increased further, there is no further increase in developed tension.
The latter remains the same despite further increase in preload. This plateau
response of systolic function to a higher than optimal preload may represent
the maximum that myofilament sensitivity to Ca2+ can attain as sarcomeres
are stretched precisely because the number of Tn-C molecules which are
bound to Ca2+ do not change for that level of cytosolic Ca2+.

If end-diastolic ventricular volume or preload is increased by increasing

“venous return”, the extent of shortening is increased and this is translated by
an increase in “stroke volume” from the point of lower to the point of higher
preload. As we mentioned earlier, LV end-diastolic pressure (LVEDP) can be
reliably considered as preload if LV compliance is normal. It is unreliable as
preload if LV compliance is abnormal because LVEDP will be abnormally high
(more than 10-12 mm Hg) while the preload can be normal. However, when
LV compliance is low, repeated measurements of LVEDP can be considered
as a reliable index of changes in preload if LV compliance has been constant
during the intervals of measurements. At this point in time, preload (LV end-
diastolic dimensions) is obtained at echocardiography with reasonable
accuracy and reproducibility and fewer scientists are looking at LVEDP as
preload.

The Frank-Starling relationship, also called Starling‟s Law or „the Law of the
Heart” can also be coined „LV performance dependence on preload”. It is also
a form of “heterometric autoregulation” because LV systolic function is
dependent on preload. One should keep in mind that, since the in situ LV
normally operates from an optimal initial sarcomere length of 2.0 to 2.2 µm,
which is the length from which the ventricle produces its maximal or nearly
maximal contractile force, the Frank-Starling mechanism is not operative in
the normal cardiovascular system. The Frank-Starling mechanism or the
“heterometric autoregulatory function” of the ventricle is operative in heart
failure at which time, an increase in preload may result in an improvement of
the depressed contractile force and subsequent increase in stroke volume.

A change in Contractility is a change in LV performance

independent of loading conditions
The relationship (ventricular function curve) between contractile force and
preload (Frank-Starling mechanism) is shifted upward and to the left when,
following ß-adrenergic stimulation, intracytosolic Ca2+ is increased. Similar
trends are seen when the muscle is stimulated by norepinephrine which
promotes higher loads of cytosolic Ca2+.

The maximum possible increase in contractility in the left ventricle shall

depend on the maximum possible intracellular Ca2+ loading. This maximum
intracellular Ca2+ loading is the molecular counterpart of the reserve function
of the left ventricle.

II THE FORCE-VELOCITY RELATIONSHIP

The second law that governs ventricular performance is the “Force-Velocity

Relationship.” Force is the “afterload” imposed on the ventricle and velocity is
the velocity of shortening of the ventricle. This law is characterized by an
inverse relationship between force and velocity of shortening which means
that at any given preload, if force (afterload) is decreased, velocity will
increase, so will the extent of shortening of myocardial fibers and ejection
(stroke volume).

The explanation of this relationship relates to the energy stored in the

preload. At any preload, the energetics of the next contractile force are set by
the initial sarcomere length and the level of cytosolic Ca2+. Since the
energetics of contractile force are translated into isometric tension (afterload)
and velocity of shortening, it follows that when one goes down, the other must
go up and vice versa. The Force-Velocity relationship is shifted upward and to
the right when the preload is increased.

Therefore, as afterload is reduced, the velocity of shortening increases.

When afterload is reduced to zero, the velocity of shortening is maximal
(Vmax). Vmax does not depend on the preload from which contraction is
initiated.

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Vmax is a measure of contractility:
Vmax (velocity at zero afterload) increases with an increase in inotropic state
(i.e. increased contractility) in the presence of an unchanged initial length
(preload). Vmax is a measure of contractility.

In individual cardiac muscle cells, Vmax is a measure of contractility because it

reflects changes in muscle performance not related to changes in preload or
changes in afterload. Vmax is difficult to measure clinically.

The maximum rate of pressure development in the left ventricle, dp/dt

max, in some respects, can be related to Vmax on theoretical grounds (with
certain assumptions), and is sometimes used as a measure of contractile
state. Care must be exercised when interpreting dp/dt max as an index of
contractility since it is not entirely independent of preload and afterload.

III CONTROL OF CARDIAC PUMP FUNCTION

Definition: Cardiac pump function or LV performance is simply the ability
of the heart to supply the periphery with output commensurate with peripheral
metabolic demands. It may be defined in terms of any of a number of different
performance parameters such as: cardiac output, stroke volume, rate of fiber
shortening, stroke work, ejection fraction and several others. All these
performance parameters are inter-related to varying degrees

Myocardial performance is dependent on four major factors.

1. Preload
2. Afterload
3. Heart rate
4. Contractility

Increased contractility: Positive inotropic effect. Performance

improves at any given preload and afterload. Increased contractility is
associated with increased availability of Ca++ to the contractile machinery.

Factors influencing myocardial contractility

Neural influences. Sympathetic discharge to the ventricles increases their

contractility. Likewise, circulating epinephrine increases contractility.

Metabolic conditions. Hypoxia, hypercapnia, and acidosis depress the

function of myocardial muscle cells and result in reduced contractility.

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Heart rate. As the time between heart beats decreases the contractility
increases. This is thought to be due to an increased Ca++ available to the
contractile machinery.

Treppe or staircase phenomenon. As rate is gradually increased over the

range of 20 bpm to 200 bpm the contractile force increases.

Post-extrasystolic potentiation. A premature ventricular depolarization

results in a weak contraction; however, the subsequent beat shows an
increased force of contraction. This is independent of filling. It is thought that
intracellular reuptake of Ca++ may be impaired during the weak beat.

Performance dependence on afterload. A sudden rise in afterload causes

an immediate decrease in ejection fraction and a rise in end- systolic volume.
Two compensations occur. Because increased end-systolic volume coupled
with a normal venous return leads to elevated preload, stroke volume is
maintained by Starling's Law. Thus, small changes in afterload have minimal
steady state effect on performance as measured by stroke volume or cardiac
output despite a signficant initial effect.

Effect of atrial pacing on Cardiac Output and Stroke Volume

Increasing heart rate by electrical pacing does not change cardiac output
because the increase in heart rate does not take place in response to
increased peripheral metabolic demands. However, stoke volume is seen to
decline progressively as pacing is made faster. The fall in stroke volume is
related to the Frank-Starling mechanism: Since peripheral demands are not
changed, there is no physiologic reason for cardiac output to change. But
Stroke Volume decreases steadily because preload decreases because of
pacing. It is to be noted that atrial contraction becomes a more effective
contributor to LVEDV because it now occurs early in diastole.

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Diagram of the effects on stroke volume and cardiac output of changing heart
rate by electrical pacing of the right atrium:

At very low heart rates (25-50 beats/min) the ventricle is maximally filled, and
the cardiac output progressively drops as heart rate is slowed, without a
change in the stroke volume. Over the range of 50-180/min the cardiac
output does not change appreciably, so that the stroke volume progressively
falls as heart rate is increased. Above about 180/min, the cardiac output falls
with increasing rates, probably due to impaired ventricular filling.

Ejection Fraction is the ratio of blood ejected to the total blood contained in
the ventricle at end-diastole. It is expressed as percent of LVEDV.

SV EDV  ESV
EF  
EDV EDV

where SV = Stroke Volume, EDV = End-Diastolic Volume

ESV = End-Systolic Volume