Cardiovascular Physiology
421
in pressure. The results of the refl exes are (1) heart rate is
increased through increased sympathetic and decreased para-
sympathetic discharge to the heart, and (2) total peripheral
resistance is increased by increased sympathetic discharge to
systemic arterioles as well as by increased plasma concentra-
tions of the two major hormonal vasoconstrictors—angioten-
sin II and vasopressin.
The refl ex increases in heart rate and total peripheral
resistance are initially benefi cial in restoring cardiac output
and arterial pressure, just as if the changes in these parameters
had been triggered by hemorrhage.
Maintained chronically throughout the period of cardiac
failure, the baroreceptor refl exes also bring about fl
uid reten-
tion and an expansion—often massive—of the extracellular
volume. This is because, as Chapter 14 describes, the neuroen-
docrine efferent components of the refl exes cause the kidneys
to reduce their excretion of sodium and water. The retained
fl uid then causes expansion of the extracellular volume.
Because the plasma volume is part of the extracellular fl
uid
volume, plasma volume also increases. This in turn increases
venous pressure, venous return, and end-diastolic ventricular
volume, which tends to restore stroke volume toward normal
by the Frank-Starling mechanism (see Figure 12–65). Thus,
fl uid retention is also, at least initially, an adaptive response to
decreased cardiac output.
However, problems emerge as the fl uid retention pro-
gresses. For one thing, when a ventricle with systolic dysfunc-
tion (as opposed to a normal ventricle) becomes very distended
with blood, its force of contraction actually decreases and
the situation worsens. Second, the fl
uid retention, with its
accompanying elevation in venous pressure, causes edema—
accumulation of interstitial fl
uid. Why does an increased
venous pressure cause edema? The capillaries drain via
venules into the veins; so when venous pressure increases, the
capillary pressure also increases and causes increased fi ltra-
tion of fl uid out of the capillaries into the interstitial fl
uid.
Thus, most of the fl uid retained by the kidneys ends up as
extra interstitial fl uid rather than extra plasma. Swelling of the
legs and feet is particularly prominent.
Most important in this regard, failure of the
left
ventricle—whether due to diastolic or systolic dysfunction—
leads to
pulmonary edema,
the accumulation of fl
uid in the
interstitial spaces of the lung or in the air spaces themselves,
which impairs gas exchange. The reason for such accumula-
tion is that the left ventricle fails to pump blood to the same
extent as the right ventricle, so the volume of blood in all
the pulmonary vessels increases. The resulting engorgement
of pulmonary capillaries raises the capillary pressure above its
normally very low value, causing fi ltration to occur at a rate
faster than the lymphatics can remove the fl
uid. This situa-
tion usually worsens at night. During the day, because of the
patient’s upright posture, fl uid accumulates in the legs; then
the fl uid is slowly absorbed back into the capillaries when the
patient lies down at night, thus expanding the plasma volume
and precipitating an attack of pulmonary edema.
Another component of the refl
ex response to heart fail-
ure that is at fi rst benefi cial but ultimately becomes maladap-
tive is the increase in total peripheral resistance, mediated by
the sympathetic nerves to arterioles and by angiotensin II and
vasopressin. By chronically maintaining the arterial blood
pressure the failing heart must pump against, this increased
resistance makes the failing heart work much harder.
One obvious treatment for heart failure is to correct,
if possible, the precipitating cause (for example, hyperten-
sion).
Table 12–9
lists the types of drugs most often used
for treatment. Finally, although cardiac transplantation is
often the treatment of choice, the paucity of donor hearts,
the high costs, and the challenges of postsurgical care render
it a feasible option for only a very small number of patients.
Cons
iderab
le
research
has
a
lso
been
d
irected
toward
the
development of artifi cial hearts, though success has been lim-
ited to date.
Table 12–9
Types of Drugs Used to Treat Heart Failure
1.
Diuretics:
Drugs that increase urinary excretion of sodium and water (Chapter 14). These drugs eliminate the excessive fl
uid
accumulation contributing to edema and/or worsening myocardial function.
2.
Cardiac inotropic drugs:
Drugs such as
digitalis
that increase ventricular contractility by increasing cytosolic calcium concentration in
the myocardial cell. The use of these drugs is currently controversial, however, because although they clearly improve the symptoms of
heart failure, they do not prolong life and, in some studies, seem to have shortened it.
3.
Vasodilator drugs:
Drugs that lower total peripheral resistance and thus the arterial blood pressure (afterload) the failing heart must
pump against. Some inhibit a component of the sympathetic nervous pathway to the arterioles, whereas others [angiotensin-converting
enzyme (ACE) inhibitors] block the formation of angiotensin II (see Chapter 14). In addition, the ACE inhibitors prevent or reverse
the maladaptive remodeling of the myocardium that is mediated by the elevated plasma concentration of angiotensin II in heart failure.
4.
Beta-adrenergic receptor blockers:
Drugs that block the major adrenergic receptors in the myocardium. The mechanism by which this
action improves heart failure is unknown (indeed, you might have predicted that such an action, by blocking sympathetically induced
increases in cardiac contractility, would be counterproductive). One hypothesis is that excess sympathetic stimulation of the heart
refl exly produced by the decreased cardiac output of heart failure may cause an excessive elevation of cytosolic calcium concentration,
which would lead to cell apoptosis and necrosis; beta-adrenergic receptor blockers would prevent this.
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