The signiﬁ cance of the Frank-Starling mechanism is as
follows: At any given heart rate, an increase in the
—the ﬂ ow of blood from the veins into the heart—
automatically forces an increase in cardiac output by increasing
end-diastolic volume and thus stroke volume. One impor-
tant function of this relationship is maintaining the equality
of right and left cardiac outputs. Should the right side of the
heart, for example, suddenly begin to pump more blood than
the left, the increased blood ﬂ ow to the left ventricle would
automatically produce an increase in left ventricular output.
This ensures that blood will not accumulate in the pulmo-
Sympathetic nerves are distributed to the entire myocardium.
The sympathetic neurotransmitter norepinephrine acts on beta-
adrenergic receptors to increase ventricular
defined as the strength of contraction
at any given end-
Plasma epinephrine acting on these receptors
also increases myocardial contractility. Thus, the increased
force of contraction and stroke volume resulting from sym-
pathetic nerve stimulation or epinephrine is independent of a
change in end-diastolic ventricular volume.
Note that a change in contraction force due to increased
end-diastolic volume (the Frank-Starling mechanism) does
not reﬂ ect increased contractility. Increased contractility is
speciﬁ cally deﬁ ned as an increased contraction force at
given end-diastolic volume.
The relationship between the Frank-Starling mecha-
nism and the cardiac sympathetic nerves is illustrated in
. The green ventricular function curve is the
same as that shown in Figure 12–24. The orange ventricular
function curve was obtained for the same heart during sympa-
thetic nerve stimulation. The Frank-Starling mechanism still
applies, but during nerve stimulation, the stroke volume is
greater at any given end-diastolic volume. In other words, the
increased contractility leads to a more complete ejection of the
end-diastolic ventricular volume.
One way to quantify contractility is through the
tion fraction (EF),
deﬁ ned as the ratio of stroke volume
(SV) to end-diastolic volume (EDV):
EF = SV/EDV
Expressed as a percentage, the ejection fraction normally aver-
ages between 50 and 75 percent under resting conditions.
Increased contractility causes an increased ejection fraction.
Not only does increased sympathetic nerve activity to
the myocardium cause a more powerful contraction, it also
causes both the contraction and relaxation of the ventricles to
occur more quickly (
). These latter effects are
quite important because, as described earlier, increased sym-
pathetic activity to the heart also increases heart rate. As heart
rate increases, the time available for diastolic ﬁ lling decreases,
but the quicker contraction and relaxation induced simultane-
ously by the sympathetic neurons partially compensate for this
problem by permitting a larger fraction of the cardiac cycle to
be available for ﬁ lling.
Cellular mechanisms involved in sympathetic regula-
tion of myocardial contractility are shown in
Adrenergic receptors activate a G-protein-coupled cascade that
includes the production of cAMP and activation of a protein
kinase. A number of proteins involved in excitation-contraction
Ventricular end-diastolic volume (ml)
Stroke volume (ml)
Effects on stroke volume of stimulating the sympathetic nerves to the
heart. Stroke volume is increased at any given end-diastolic volume;
that is, the sympathetic stimulation increases ventricular contractility.
From this ﬁ gure, estimate the ejection fraction and end-systolic
volumes under control and sympathetic stimulation conditions at
an end-diastolic volume of 140 mL.
Answer can be found at end of chapter.
Effects of sympathetic stimulation on ventricular contraction and
relaxation. Note that both the rate of force development and the rate
of relaxation increase, as does the maximum force developed. All
these changes reﬂ ect an increased contractility.
of sympathetic nerves