Human Physiology, 14th edition (2016)

454 Chapter 14

inotropic effect on contractility and (2) through a positive chro-

notropic effect on cardiac rate ( fig.  14.5 ). Stimulation through

parasympathetic nerve endings to the SA node and conducting

tissue has a negative chronotropic effect but does not directly

affect the contraction strength of the ventricles. However,

the increased EDV that results from a slower cardiac rate can

increase contraction strength through the mechanism described

by the Frank-Starling law of the heart. This increases stroke vol-

ume, but not enough to completely compensate for the slower

cardiac rate. Thus, the cardiac output is decreased when the heart

beats slower, a fact used by people who treat their hypertension

with beta-adrenergic blocking drugs that slow the cardiac rate.

Venous Return

The end-diastolic volume—and thus the stroke volume and

cardiac output—is controlled by factors that affect the venous

return, which is the return of blood to the heart via veins. The

rate at which the atria and ventricles are filled with venous

blood depends on the total blood volume and the venous pres-

sure (pressure in the veins). It is the venous pressure that serves

as the driving force for the return of blood to the heart.

As the ventricles fill with blood, the myocardium stretches so
that the actin filaments overlap with myosin only at the edges of
the A bands ( fig. 14.3 ). This increases the number of interactions
between actin and myosin, allowing more force to be developed
during contraction. Also, stretching of myocardial cells during
diastole increases the sensitivity of the Ca^2 1 -release channels
in the sarcoplasmic reticulum (SR), promoting their release of
Ca^2 1 in response to stimulation (chapter 12; see fig. 12.34). This
greater release of Ca^2 1 results in a stronger contraction.
The Frank-Starling mechanism results in the initial rapid
increase in contractility when the ventricles are stretched. However,
the force of myocardial contraction then gradually increases over
the next 10–15 minutes following stretching of the ventricles. This
is known as the Anrep effect, and appears to be due to increased
Ca^2 1 entering the cytoplasm through the Na^1 /Ca^2 1 exchanger
(chapter 12, section 12.5). Because the degree of myocardial
stretching depends on the end-diastolic volume, these mechanisms
ensure that an increase in end-diastolic volume intrinsically pro-
duces an increase in contraction strength and stroke volume.
As shown in figure  14.4 , muscle length has a more pro-
nounced effect on contraction strength in cardiac muscle than
in skeletal muscle. That is, a particular increase in sarcomere
length will stimulate contraction strength more in cardiac mus-
cle than in skeletal muscle. This is believed to be due to an
increased sensitivity of stretched cardiac muscle to the stimu-
latory effects of Ca^2 1.
The Frank-Starling law explains how the heart can adjust
to a rise in total peripheral resistance: (1) a rise in peripheral
resistance causes a decrease in the stroke volume of the ven-
tricle, so that (2) more blood remains in the ventricle and the
end-diastolic volume is greater for the next cycle; as a result,
(3) the ventricle is stretched to a greater degree in the next
cycle and contracts more strongly to eject more blood. This
allows a healthy ventricle to sustain a normal cardiac output
when there are changes in the total peripheral resistance.
A very important consequence of these events is that the
cardiac output of the left ventricle, which pumps blood into
the systemic circulation with its ever-changing resistances, can
be adjusted to match the output of the right ventricle (which
pumps blood into the pulmonary circulation). The rate of blood
flow through the pulmonary and systemic circulations must be
equal to prevent fluid accumulation in the lungs and to deliver
fully oxygenated blood to the body.

Extrinsic Control of Contractility

Contractility is the strength of contraction at any given fiber
length. At any given degree of stretch, the strength of ventricu-
lar contraction depends on the activity of the sympathoadrenal
system. Norepinephrine from sympathetic nerve endings and
epinephrine from the adrenal medulla produce an increase in
contraction strength (see figs. 14.2 and 14.4 ). This positive
inotropic effect results from an increase in the amount of Ca^2 1
available to the sarcomeres.
The cardiac output is thus affected in two ways by the
activity of the sympathoadrenal system: (1) through a positive

Figure 14.4 The effect of muscle length and

epinephrine on contraction strength. In this schematic

comparison, all three curves demonstrate that each muscle

contracts with its maximum force (100% relative tension) at its

own optimum length (100% optimum length). As the length is

decreased from optimum, each curve demonstrates a decreased

contraction strength. Notice that the decline is steeper for

cardiac muscle than for skeletal muscle, demonstrating the

importance of the Frank-Starling relationship in heart physiology.

At any length, however, epinephrine increases the strength of

myocardial contraction, demonstrating a positive inotropic effect.

0

50 60 70 80 90 100

80

60

40

20

100

Relative tension (%)

Cardiac muscle

without epinephrine

Cardiac muscle

with epinephrine

(inotropic effect)

Skeletal muscle

Length of muscle (as percent of optimum at 100%)