Page 755 - Fundamentals of anatomy physiology

742 Unit 4 Fluids and Transport
20 The EDV and Stroke Volume. In general, the greater the EDV,
the larger the stroke volume. Stretching the cardiac muscle cells
past their optimal length would reduce the force of contraction,
but this degree of stretching does not normally take place.
Myocardial connective tissues, the cardiac skeleton, and the
pericardial sac all limit the expansion of the ventricles.
The relationship between the amount of ventricular stretch-
ing and the contractile force means that, within normal physi-
ological limits, increasing the EDV results in a corresponding
increase in the stroke volume. This general rule of “more in 5
more out” was first proposed by Ernest H. Starling based on his
studies and research by Otto Frank. The relationship is known
as the Frank–Starling principle, or Starling’s law of the heart.
Autonomic adjustments to cardiac output normally make
the effects of the Frank–Starling principle difficult to see. How-
ever, we can see the effects more clearly in individuals who
have received a heart transplant, because the implanted heart
is not innervated by the ANS. The most obvious effect of the
Frank–Starling principle in these hearts is that the outputs of
the left and right ventricles remain balanced under a variety of
conditions.
Consider, for example, an individual at rest, with the two
ventricles ejecting equal volumes of blood. Although the ven-
tricles contract together, they work in series: When the heart
contracts, blood leaving the right ventricle heads to the lungs.
During the next ventricular diastole, that volume of blood
passes through the left atrium, to be ejected by the left ventricle
at the next contraction. If the venous return decreases, the EDV
of the right ventricle will decline. During ventricular systole, the
right ventricle will then pump less blood to the lungs. In the
next cardiac cycle, the EDV of the left ventricle will be reduced,
and that ventricle will eject a smaller volume of blood. The out-
put of the two ventricles will again be in balance, but both will
have smaller stroke volumes than they did initially.
The ESV
After the ventricle has contracted and ejected the stroke volume,
the amount of blood that remains in the ventricle at the end
of ventricular systole is the ESV. Three factors that influence the
ESV are the preload (discussed earlier), the contractility of the
ventricle, and the afterload.
Contractility. Contractility is the amount of force produced
during a contraction, at a given preload. Under normal cir-
cumstances, autonomic innervation or circulating hormones
can alter contractility. Under special circumstances, drugs or
abnormal ion concentrations in the extracellular fluid can alter
contractility.
Factors that increase contractility are said to have a positive
inotropic action (ino-, fiber). Factors that decrease contractil-
ity have a negative inotropic action. Positive inotropic agents
typically stimulate Ca21 entry into cardiac muscle cells, thus
increasing the force and duration of ventricular contractions.
Negative inotropic agents may block Ca21 movement or de-
press cardiac muscle metabolism. Positive and negative ino-
tropic factors include ANS activity, hormones, and changes in
extracellular ion concentrations.
Effects of Autonomic Activity on Contractility. Autonomic ac-
tivity alters the degree of contraction and changes the ESV in
the following ways:
Sympathetic stimulation has a positive inotropic effect.
It causes the release of norepinephrine (NE) by postgan-
glionic fibers of the cardiac nerves and the secretion of
epinephrine (E) and NE by the adrenal medullae. These
hormones affect heart rate, as we will discuss shortly. They
also stimulate alpha and beta receptors in cardiac muscle
plasma membranes. This stimulation increases cardiac
muscle cell metabolism and the force and degree of con-
traction. The net effect is that the ventricles contract more
forcefully, increasing the ejection fraction and decreasing
the ESV.
Parasympathetic stimulation from the vagus nerves has a
negative inotropic effect. The primary effect of acetylcho-
line (ACh) is at the membrane surface, where it produces
hyperpolarization and inhibition. As a result, the force of
cardiac contractions is reduced. The atria show the greatest
changes in contractile force because the ventricles are not
extensively innervated by the parasympathetic division.
However, under strong parasympathetic stimulation or
after the administration of drugs that mimic the actions
of ACh, the ventricles contract less forcefully, the ejection
f­raction decreases, and the ESV becomes larger.
Hormones. Many hormones affect the contractility of the
heart. For example, epinephrine, norepinephrine, and thyroid
hormones all have positive inotropic effects. Glucagon also has
a positive inotropic effect. Before synthetic inotropic agents
were available, glucagon was widely used to stimulate cardiac
function. It is still used in cardiac emergencies and to treat some
forms of heart disease.
The drugs isoproterenol, dopamine, and dobutamine mimic
the action of E and NE by stimulating beta-1 receptors on
cardiac muscle cells. p. 567 Dopamine (at high doses) and
dobutamine also stimulate Ca21 entry through alpha-1 recep-
tor stimulation. Digitalis and related drugs elevate intracellu-
lar Ca21 concentrations, but by a different mechanism. They
interfere with the removal of Ca21 from the cytosol of cardiac
muscle cells.
Many of the drugs used to treat hypertension (high blood
pressure) have a negative inotropic action. Beta-blocking drugs
such as propranolol, timolol, metoprolol, atenolol, and labetalol block
beta receptors, alpha receptors, or both, and prevent sympathetic