74
CARDIOVASCULAR PHYSIOLOGY CONCEPTS
sarcomere lengths (1.8 to 2.2 |J,m). These
and other observations have led to the con-
cept of length-dependent activation. Exper-
imental evidence supports three possible
explanations. First, studies have shown that
increased sarcomere length sensitizes the
regulatory protein troponin C to calcium
without necessarily increasing intracellular
release of calcium. This increases calcium
binding by troponin C, leading to an increase
in force generation as described in Chapter
3. A second explanation is that fiber stretch-
ing alters calcium homeostasis within the
cell so that increased calcium is available to
bind to troponin C. A third explanation is
that as a myocyte (and sarcomere) length-
ens, the diameter must decrease because the
volume has to remain constant. It has been
proposed that this would bring the actin
and myosin molecules closer to each other
(decreased lateral spacing), which would
facilitate their interactions.
Effects of Venous Return on
Stroke Volume (Frank-Starling
Mechanism)
Altered preload is an important mechanism
by which the ventricle changes its force
of contraction and therefore its SV When
venous return to
the heart is increased,
ventricular filling increases, and therefore
its preload. This stretching of the myocytes
causes an increase in force generation, which
enables the heart to eject the additional
venous return and thereby increase SV. This
is called the Frank-Starling mechanism in
honor of the scientific contributions of Otto
Frank (late 19th century) and Ernest Starling
(early 20th century). Another term for this
mechanism is “Starling’s law of the heart.”
In summary,
the Frank-Starling mechanism
states that increasing venous return and ven-
tricular preload leads to an increase in SV
.
Figure 4.10 shows the Frank-Starling rela-
tionship for the left ventricle. Assume that
the left ventricle is normally operating at
an end-diastolic pressure of 8 mm Hg and
is ejecting an SV of 70 mL (Point A). If the
■ FIGURE 4.10 Frank-Starling mechanism.
Increasing venous return to the left ventricle
increases left ventricular end-diastolic pres-
sure
(LVEDP)
by increasing ventricular volume;
this increased preload increases stroke volume
(SV)
from point
A
(normal operating point) to
B.
Decreasing venous return decreases preload and
stroke volume (point
C).
venous return to the heart is increased and
the end-diastolic pressure is increased, this
will lead to an increase in SV (Point B). A
decrease in venous return (Point C) would
result in less ventricular filling, leading to a
lower end-diastolic pressure and a reduced
SV along this Frank-Starling curve.
The Frank-Starling mechanism plays an
important role in balancing the output of the
two ventricles. For example, when venous
return increases to the right side of the heart
during physical activity, the Frank-Starling
mechanism enables the right ventricular SV
to increase, thereby matching its output to
the increased venous return. The increased
right ventricular output increases the venous
return to the left side of the heart, and the
Frank-Starling mechanism operates to increase
the output of the left ventricle. This mecha-
nism ensures that the outputs of the two ven-
tricles are matched over time; otherwise blood
volume would shift between the pulmonary
and systemic circulations.
This analysis using Frank-Starling curves
shows how changes in venous return and ven-
tricular preload lead to changes in SV. These
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