82
CARDIOVASCULAR PHYSIOLOGY CONCEPTS
■ FIGURE 4.22 Effects of increasing inotropy
on steady-state left ventricular pressure-volume
loops. Increased inotropy shifts the ESPVR (see Fig.
4.4) up and to the left, thereby increasing stroke
volume and decreasing end-systolic volume
(ESV).
Decreased inotropy shifts the end-diastolic pres-
sure-volume relationship down and to the right,
thereby decreasing stroke volume and increasing
end-systolic volume.
LV,
left ventricle. Preload and
aortic pressure are held constant in this illustration.
inotropy increases EF, whereas decreasing
inotropy decreases EF Therefore,
EF often is
used as a clinical index for evaluating the ino-
tropic state of the heart.
Factors Influencing
Inotropic State
Several
factors
influence
ventricular
inot-
ropy (Fig. 4.23); the most important of these
is the activity of sympathetic nerves. Sympa-
thetic nerves, by releasing norepinephrine that
binds to Pj-adrenoceptors on myocytes, serve
a prominent role in ventricular and atrial ino-
tropic regulation (see Chapter 3). Elevated lev-
els of circulating catecholamines (epinephrine
TSympathetic
Circulating
Activation
Catecholamines
Afterload
Heart Rate
(Anrep Effect)
(Bowditch Effect)
■ FIGURE 4.23 Factors that increase inotropy.
and norepinephrine) have positive inotropic
effects similar to sympathetic activation. In
humans and some other mammalian hearts, an
abrupt increase in afterload can cause a modest
increase in ino-tropy (Anrep effect) by a mecha-
nism that is not fully understood. In addition,
an increase in heart rate can cause a positive ino-
tropic effect (also termed the Bowditch effect,
treppe,
or
frequency-dependent
activation).
This latter phenomenon probably is due to an
inability of the Na+
/K+-ATPase to keep up with
the sodium influx at the higher frequency of
action potentials at elevated heart rates, leading
to an accumulation of intracellular calcium via
the sodium-calcium exchanger (see Chapter 2).
Increased inotropy brought about by sym-
pathetic activation and increased heart rate
is particularly important during exercise (see
Chapter 9) because it helps to maintain SV at
high heart rates. Recall that increased heart
rate alone decreases SV because reduced dias-
tolic filling time decreases EDV When ino-
tropic state increases at the same time, this
decreases ESV to help maintain SV despite
reduced EDV
Systolic failure that results from cardio-
myopathy, ischemia, valve disease, arrhyth-
mias, and other conditions is characterized
by a loss of intrinsic inotropy (see Chapter 9).
Furthermore, there are many inotropic drugs
that are used clinically to increase inotropy
in acute and chronic heart failure. These
drugs include
digoxin
(inhibits sarcolem-
mal Na+/K+-ATPase), P-adrenoceptor agonists
(e.g., dopamine, dobutamine, epinephrine,
isoproterenol), and cAMP-dependent phos-
phodiesterase inhibitors (e.g., milrinone).
Although the above discussion focuses on
the regulation of ventricular inotropy, it is
important to note that many of these same
factors influence atrial inotropy. Unlike the
ventricles, the atria are richly innervated with
parasympathetic
nerves
(vagal
efferents),
and activation of this autonomic pathway
decreases atrial inotropy.
Cellular Mechanisms of Inotropy
As previously stated, inotropy can be thought
of as a length-independent activation of the
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