160
CARDIOVASCULAR PHYSIOLOGY CONCEPTS
Coronary blood flow is primarily regulated
by changes in tissue metabolism.
Adenosine
has been shown to be important in dilating
the coronary vessels when the myocardium
becomes hypoxic or when cardiac metabolism
increases
during
increased
cardiac
work.
Experimental studies have shown that inhib-
iting
adenosine
formation,
enhancing
its
breakdown to inosine, or blocking vascular
adenosine receptors impairs coronary vaso-
dilation under these conditions. In addition,
nitric oxide has been shown to be important
in coronary vessels, particularly in producing
flow-dependent vasodilation. Finally, there is
also some evidence that prostaglandins play a
role in regulating coronary blood flow.
Coronary vessels are innervated by both
sympathetic
and
parasympathetic
nerves.
Unlike most other vascular beds, activation
of sympathetic nerves to the heart causes
only
transient
coronary
vasoconstriction
(a-adrenoceptor mediated) followed by vaso-
dilation.
The
vasodilation
occurs
because
sympathetic
activation
of
the
heart
also
increases heart rate and inotropy through
P-adrenoceptors, which leads to enhanced
production
of vasodilator metabolites
that
inhibit the vasoconstrictor response and cause
vasodilation. This is termed functional sym-
patholysis. If P-adrenoceptors are blocked
experimentally,
sympathetic
stimulation
of
the heart causes coronary vasoconstriction.
Parasympathetic stimulation of the heart (i.e.,
vagal nerve activation) elicits modest coro-
nary vasodilation owing to the direct effects of
released acetylcholine on the coronaries. How-
ever, if parasympathetic activation of the heart
results in a significant decrease in myocardial
oxygen demand, local metabolic mechanisms
increase coronary vascular tone (i.e., cause
vasoconstriction). Therefore, parasympathetic
activation of the heart generally results in a
decrease in coronary blood flow, although the
direct effect of parasympathetic stimulation of
the coronary vessels is vasodilation.
INSUFFICIENT CORONARY BLOOD FLOW
Coronary blood flow is crucial for the nor-
mal function of the heart. Because of the high
oxygen consumption of the beating heart
(see Chapter 4) and the fact that the heart
relies on oxidative metabolism (see Chapter
3), coronary blood flow (oxygen delivery) and
the metabolic activity of the heart need to be
tightly coupled. This is all the more important
because, as discussed in Chapter 4, the beat-
ing heart extracts more than half of the oxy-
gen from the arterial blood; therefore, there
is relatively little oxygen extraction reserve.
In coronary artery disease, chronic narrowing
of the vessels or impaired vascular function
reduces maximal coronary blood flow (i.e.,
there is reduced vasodilator reserve). When
this occurs, coronary flow fails to increase
adequately as myocardial oxygen demands
increase (Fig.
7.8).
This leads to
cardiac
hypoxia and impaired contractile function.
The relationship between coronary blood
flow and the metabolic demand of the heart is
often discussed in terms of the myocardial oxy-
gen supply/demand ratio. The oxygen supply
is the amount of oxygen delivered per minute
to the myocardium in the arterial blood (mL
O2/min), which is the product of the coronary
blood flow (mL blood/min) and arterial oxy-
gen content (mL O2/mL blood). The oxygen
demand of the heart is the myocardial oxygen
consumption, which is the product of coro-
nary blood flow and the difference between
the
arterial
and
venous
oxygen
contents
■ FIGURE 7.8 Relationship between coronary
blood flow and myocardial oxygen consumption.
Coronary blood flow increases as myocardial
oxygen consum ption increases. However, if the
coronary vessels are diseased and have increased
resistance owing to stenosis
(red line),
blood flow
(and therefore oxygen delivery) will be lim ited at
higher oxygen consumptions, leading to an oxy-
gen deficit and myocardial hypoxia.
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