The Cardiovascular System: The Heart
thyroxine, and glucagon; the drug digitalis; and high levels of
are all positive inotropic agents.
which impair or decrease contractility, include
acidosis (excess H
), rising extracellular K
levels, and drugs
called calcium channel blockers.
Afterload: Back Pressure Exerted by Arterial Blood
is the pressure that the ventricles must overcome to eject
blood. It is essentially the back pressure that arterial blood ex-
erts on the aortic and pulmonary valves—about 80 mm Hg in
the aorta and 10 mm Hg in the pulmonary trunk.
In healthy individuals, aFerload is not a major determinant
of stroke volume because it is relatively constant. However, in
people with hypertension (high blood pressure), aFerload is
important indeed because it reduces the ability of the ventricles
to eject blood. Consequently, more blood remains in the heart
aFer systole, increasing ESV and reducing stroke volume.
Regulation of Heart Rate
Given a healthy cardiovascular system, SV tends to be relatively
constant. However, when blood volume drops sharply or the
heart is seriously weakened, SV declines and CO is maintained
by increasing HR and contractility. Temporary stressors can
begins to pump more blood than the other, the increased venous
return to the opposite ventricle forces that ventricle—through
increased cardiac muscle stretch—to pump out an equal volume,
preventing backup or accumulation of blood in the circulation.
EDV is the major
that increase heart muscle contractility
can also enhance SV.
is deﬁned as the contractile
strength achieved at a given muscle length. Note in ±igure 18.22
that contractility is
of muscle stretch and EDV. Con-
tractility rises when more Ca
enters the cytoplasm from the ex-
tracellular ﬂuid and the SR. Enhanced contractility means more
blood is ejected from the heart (greater SV), hence a lower ESV.
Increased sympathetic stimulation increases contractility. As
noted on p. 676, sympathetic ﬁbers serve not only the intrinsic
conduction system but the entire heart. One eﬀect of norepine-
phrine or epinephrine binding is to initiate a cyclic AMP second-
messenger system that increases Ca
entry, which in turn pro-
motes more cross bridge binding and enhances ventricular con-
A battery of other chemicals also inﬂuence contractility.
Substances that increase contractility are called
muscle, ﬁber). ²e hormones epinephrine,
G protein (G
Phosphorylates SR Ca
removal and relaxation, making more
available for release on the next beat
Phosphorylates SR Ca
force and velocity
ATP is converted
Norepinephrine increases heart contractility via a cyclic AMP second-
Cyclic AMP activates protein kinases that phosphorylate three different
proteins, as shown in