(see Equation 4-3). A decrease in the oxygen
supply/demand ratio causes tissue hypoxia,
which can result in chest pain (angina pecto-
ris). This can occur by a decrease in oxygen
supply (decreased coronary blood flow or arte-
rial oxygen content), an increase in myocardial
oxygen consumption, or a combination of the
two. One of the therapeutic goals for people
who have coronary artery disease and anginal
pain is to increase the oxygen supply/demand
ratio either by improving coronary flow (e.g.,
coronary bypass grafts or coronary stent place-
ment) or by decreasing myocardial oxygen
consumption by reducing heart rate, inotropy,
preload, and afterload (see Chapter 4).
Both structural and functional changes
occur when coronary arteries become dis-
eased. Atherosclerotic processes decrease the
lumen diameter, causing stenosis. This com-
monly occurs in the large epicardial arteries,
although the disease also afflicts small vessels.
The large coronary arteries ordinarily repre-
sent only a very small fraction of total coro-
nary vascular resistance. Therefore, stenosis
in these vessels needs to exceed a 60% to 70%
reduction in lumen diameter (i.e., exceed the
critical stenosis) to have significant effects on
resting blood flow and maximal flow capacity
(see Chapter 5).
In addition to narrowing the lumen and
increasing resistance to flow, atherosclero-
sis causes endothelial damage and dysfunc-
tion. This leads to reduced nitric oxide and
prostacyclin formation, which can precipitate
coronary vasospasm and thrombus formation,
leading to increased vascular resistance and
decreased flow. Loss of these endothelial fac-
tors impairs vasodilation, which decreases the
vasodilator reserve capacity. When coronary
flow is compromised by coronary artery dis-
ease either at rest or during times of increased
metabolic demand (e.g., during exercise),
the myocardium becomes hypoxic, which
can impair mechanical function, precipitate
arrhythmias, and produce angina.
When coronary oxygen delivery is lim-
ited by disease, collateral vessels can play an
important adjunct role in supplying oxygen to
the heart. Conditions of chronic stress (e.g.,
chronic hypoxia or exercise training) stimulate
the process of angiogenesis, which causes
new blood vessels to form. Collateralization
increases myocardial blood supply by increas-
ing the number of parallel vessels, thereby
reducing vascular resistance within the myo-
cardium. This helps to supply blood flow to
ischemic regions caused by vascular stenosis or
CASE 7-1
A patient with known coronary artery
disease (stenosis of multiple vessels) is
also hypertensive. Explain why blood
pressure-lowering drugs that produce
reflex tachycardia should be not be used
in such a patient.
Cerebral Circulation
The brain is a highly oxidative organ that
consumes almost 20% of resting total-body
oxygen consumption. To deliver adequate
oxygen, the cerebral blood flow needs to be
relatively high, about 50 to 60 mL/min per
100 g tissue weight (see Table 7-1). Although
the brain represents only about 2% of body
weight, it receives approximately 14% of the
cardiac output.
The brain circulation is supplied by four prin-
cipal arteries: the left and right carotid arter-
ies and the left and right vertebral arteries
(Fig. 7.9). The vertebral arteries join together
on the ventral surface of the pons to form
the basilar artery, which then travels up the
brainstem to join the carotid arteries through
interconnecting arteries, forming the Circle
of Willis. Arterial vessels originating from
the vertebral and basilar arteries as well as the
Circle of Willis distribute blood flow to differ-
ent regions of the brain. This interconnecting
network of arterial vessels at the brainstem
provides a safety mechanism for cerebral perfu-
sion. If, for example, a carotid artery becomes
partly occluded and flow is reduced through
that artery, increased flow through the other
interconnecting arteries can help improve per-
fusion of the affected portion of the brain.
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