420
Chapter 12
standard practice to separate people with heart failure into
two categories: (1) those with diastolic dysfunction (problems
with ventricular fi lling) and (2) those with systolic dysfunction
(problems with ventricular ejection). Many people with heart
failure, however, exhibit elements of both categories.
In
diastolic dysfunction,
the wall of the ventricle has
reduced compliance. That is, it is abnormally stiff and there-
fore has a reduced ability to fi ll adequately at normal diastolic
fi lling pressures. The result is a reduced end-diastolic volume
(even though the end-diastolic pressure in the stiff ventricle
may be quite high) and, therefore, a reduced stroke volume
by the Frank-Starling mechanism. Note that in pure diastolic
dysfunction, ventricular compliance is decreased, but ventric-
ular contractility is normal.
Several situations may lead to decreased ventricular
compliance, but by far the most common is the existence of
systemic hypertension. As noted in the previous section, the
left ventricle, pumping chronically against an elevated arte-
rial pressure, hypertrophies. The structural and biochemical
changes associated with this hypertrophy make the ventricle
stiff and less able to expand.
In contrast to diastolic dysfunction,
systolic dysfunction
results from myocardial damage due, for example, to a heart
attack (discussed next). This type of dysfunction is characterized
by a decrease in cardiac contractility—a lower stroke volume at
any given end-diastolic volume. This is manifested as a decrease
in ejection fraction and, as illustrated in
Figure 12–65
, a down-
ward shift of the ventricular function curve. The affected ven-
tricle does not hypertrophy, but note that the end-diastolic
volume increases.
The reduced cardiac output of heart failure, regardless
of whether it is due to diastolic or systolic dysfunction, trig-
gers the arterial baroreceptor refl exes. In this situation these
refl exes are elicited more than usual because, for unknown
reasons, the afferent baroreceptors are less sensitive. In other
words, the baroreceptors discharge less rapidly than normal
at any given mean or pulsatile arterial pressure, and the brain
interprets this decreased discharge as a larger-than-usual fall
Table 12–8
Drugs Used to Treat Hypertension
1.
Diuretics:
These drugs increase urinary excretion of sodium and water (Chapter 14). They tend to decrease cardiac output with little or
no change in total peripheral resistance.
2.
Beta-adrenergic receptor blockers:
These drugs exert their antihypertensive effects mainly by reducing cardiac output.
3.
Calcium channel blockers:
These drugs reduce the entry of calcium into vascular smooth muscle cells, causing them to contract less
strongly and lowering total peripheral resistance. (Surprisingly, it has been found that despite their effectiveness in lowering blood
pressure, at least some of these drugs may signifi cantly increase the risk of a heart attack. Consequently, their use as therapy for
hypertension is now under intensive review.)
4.
Angiotensin-converting enzyme (ACE) inhibitors:
As Chapter 14 will describe, the fi nal step in the formation of angiotensin II, a
vasoconstrictor, is mediated by an enzyme called angiotensin-converting enzyme. Drugs that block this enzyme therefore reduce the
concentration of angiotensin II in plasma, which causes arteriolar vasodilation, lowering total peripheral resistance. The same effect can
be achieved with drugs that block the receptors for angiotensin II. A reduction in plasma angiotensin II or blockage of its receptors is
also protective against the development of heart wall changes that lead to heart failure.
5. Drugs that antagonize one or more components of the sympathetic nervous system: The major effect of these drugs is to reduce
sympathetic mediated stimulation of arteriolar smooth muscle and thereby reduce total peripheral resistance. Examples include drugs
that inhibit the brain centers that mediate the sympathetic outfl ow to arterioles, and drugs that block alpha-adrenergic receptors on the
arterioles.
200
100
0
100
200
300
400
500
End-diastolic ventricular volume (ml)
Stroke volume (ml)
After fluid retention
Normal
resting
value
Before fluid retention
Normal heart
Failing heart
Figure 12–65
Relationship between end-diastolic ventricular volume and stroke
volume in a normal heart and one with heart failure due to systolic
dysfunction (decreased contractility). The normal curve was shown
previously in Figure 12–24. With decreased contractility, the
ventricular function curve is displaced downward; that is, there
is a lower stroke volume at any given end-diastolic volume. Fluid
retention causes an increase in end-diastolic volume and restores
stroke volume toward normal by the Frank-Starling mechanism.
Note that this compensation occurs even though contractility—the
basic defect—has not been altered by the fl uid retention.
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