Coronary Circulation

The myocardial blood supply comes from the

two coronary arteries that arise from the aortic
root (B,D). Usually the right coronary artery
supplies most of the right ventricle, the left
one most of the left ventricle. The contribution
of the two arteries to the supply of the interventricular
septum and the posterior wall of
the left ventricle varies.
Coronary blood flow,Q˙ cor, has a few special
features:
1. Phasic flow.Q˙ cor changes markedly during
the cardiac cycle (A), especially due to the
high tissue pressure during systole that, in
areas close to the endocardial regions of the
left ventricle, reaches ca. 120mmHg (B).
While the main epicardial branches of the coronary
arteries and the flow in the subepicardial
regions are largely unaffected by this
(B), vessels near the endocardium of the
left ventricle are “squeezed” during systole,
because during this phase the extravascular
pressure (left ventricular pressure) surpasses
the pressure in the lumen of the coronary arteries.
Blood supply to the left ventricle is
therefore largely limited to the diastole (A).
Conversely, the high systolic tissue pressure
presses the blood out of the coronary sinus
and other veins, so that most of it flows into
the right occurs during systole.
2. Adaptation to O2 demand is achieved
largely by changes in vascular resistance. O2 demand
of an organ can be calculated from the
blood flow through it,Q˙ , multiplied by the arteriovenous
O2 concentration difference (Ca –
Cv)O2. If O2 demand rises, for example, through
physical activity or hypertension (C, right
and p. 218), both variables may in principle be
increased, but (Ca – Cv)O2 and thus oxygen extraction
(= 100 · [(Ca – Cv)/Ca]O2) 60%) is very
high even at rest. During physical work, O2
supply to the myocardium, and thus cardiac
work, can essentially only be increased by an
increase inQ˙ cor (= aortic pressure PAo/coronary
resistance Rcor). If PAo remains unchanged, Rcor
must be reduced (vasodilation; C, left),
which is normally possible down to ca. 20–
25% of the resting value (coronary reserve). In
this way Q˙ cor can be increased up to four to
five times the resting value, i.e., it will be able
to meet the ca. four to fivefold increase in O2
demand of the heart at maximal physical
work (p. 219 A, normal).
3.Q˙ cor is closely linked to myocardial O2 demand.
The myocardium works aerobically, i.e.,
there must be a rapid and close link between
the momentary energy demand andQ˙ cor. Several
factors are involved in this autoregulation:
! Metabolic factors. First of all, O2 acts as a vasoconstrictor,
i.e., O2 deficiency dilates the coronary
arteries. AMP, a metabolic breakdown
product of ATP, cannot be sufficiently regenerated
to ATP during hypoxia, and thus the concentration
of AMP and its breakdown product
adenosine rises in the myocardium. Adenosine
acts as a vasodilator on the vascular musculature
via A2 receptors (cAMP increase). Finally,
the accumulation of lactate and H+ ions (both
of them products of the anaerobic myocardial
metabolism; p. 219 C) as well as prostaglandin
I2 will locally cause vasodilation.
! Endothelium-mediated factors. ATP (e.g.,
from thrombocytes), ADP, bradykinin, histamine,
and acetylcholine are vasodilators. They
act indirectly by releasing nitric oxide (NO) that
secondarily diffuses into the vascular muscle
cells, where it increases guanylylcyclase activity,
and thus intracellularly raises the concentration
of cyclic guanosine monophosphate
(cGMP). Finally, cGMP activates protein kinase
G, which relaxes the vascular musculature.
! Neurohumoral factors. Epinephrine and norepinephrine,
circulating and released from the
sympathetic nerve fiber endings, respectively,
act as vasoconstrictors on the 1-adrenoreceptors
that prevail in epicardial vessels, and as vasodilators
at -adrenoceptors that predominate
in subendocardial vessels.
If O2 supply can no longer keep in step with
oxygen demand, for example, at a high heart
rate with a long systole, or in atherosclerotic
obstruction of the coronary arteries, coronary
isufficiency (hypoxia) results (C,D and
p. 218ff.).

216
Coronary Heart Disease
During physical work or psychological stress,
the myocardial oxygen demand rises, particularly
because heart rate and myocardial contractility
will have been increased by sympathetic
stimulation. In response to this the coronary
vascular resistance can in the normal
heart drop to as low as ca. 20% of its resting
level so that, with the corresponding increase
in coronary perfusion, the O2 balance will be
restored even during this period of increased
demand. The capacity to increase perfusion to
up to five times the resting value is called coronary
reserve. The wide range in coronary
blood flow is due to the fact that the distal coronary
vessels are constricted at rest and dilate
only on demand (A; normal vs. 14 resistance).
Diminished coronary reserve is characteristic
of coronary heart disease (CHD) and leads
to O2 supply no longer being able to meet any
increased O2 demand. This ischemic anoxia
manifests itself in painmainly in the left chest,
arm, and neck during physical work or psychological
stress (angina pectoris; see below)
The main cause of CHD is narrowing of the
proximal large coronary arteries by atherosclerosis
(p. 217 D and 236ff.). The poststenotic
blood pressure (Pps) is therefore significantly
lower than mean diastolic aortic pressure
(PAo; A). To compensate for this raised
resistance or reduced pressure, the coronary
reserve is encroached upon, even at rest. The
price paid for this is a diminution in the range
of compensatory responses, which may ultimately
be used up. When the luminal diameter
of the large coronary arteries is reduced by
more than 60–70% and the cross-sectional
area is thus reduced to 10–15% of normal,
myocardial ischemia with hypoxic pain occurs
even on mild physical work or stress. If synchronously
O2 supply is reduced, for example,
by a lowered diastolic blood pressure (hypotension,
aortic regurgitation), arterial hypoxemia
(staying at high altitude), or decreased
O2 capacity (anemia), O2 balance is disturbed,
even when there is only mild coronary artery
stenosis (p. 217 C).
If the pain ceases when the physical or psychological
stress is over, the condition is called
stable angina pectoris. When a patient with
chronic stable angina pectoris suddenly has
stronger and more frequent anginal pain (unstable
angina pectoris), it is often a premonitory
sign of acute myocardial infarction, i.e.,
complete occlusion of the relevant coronary
artery (see below).
However, complete coronary occlusion does
not necessarily lead to infarction (see below),
because in certain circumstances a collateral
blood supply may develop as long-term adaptation
so that, at least at rest, the O2 demand
can be met (B). The affected region will,
however, be particularly in danger in cases of
hypoxemia, a drop in blood pressure, or an increased
O2 demand.
Pain resulting from a lack of O2 can also occur
at rest due to a spasm (1-adrenoreceptors;
p. 216) in the region of an only moderate
atherosclerotic narrowing of the lumen (vasospastic,
Prinzmetal’s, or variant angina). While
shortening of the arterial muscle ring by, for
example, 5% increases the resistance of a normal
coronary artery about 1.2fold, the same
shortening in the region of an atheroma that
is occluding 85% of the lumen will increase
the resistance 300 times the normal value
(D). There are even cases in which it is largely
(or rarely even exclusively) a coronary
spasm and not the atheromatous occlusion
that leads to an episode of vasospastic angina.
Another cause of diminished coronary reserve
is an increased O2 demand even at rest,
for example, in hypertension or when there is
an increased ventricular volume load. The
ventricular wall tension, i.e., the force that the
myocardium must generate perwall cross-sectional
area (N ·m– 2) to overcome an elevated
aortic pressure or to eject the increased filling
volume, is then significant. In accordance with
Laplace’s law, the wall tension (K) of an approximately
spherical hollow organ can be calculated
from the ratio of (transmural pressure
· radius)/(2 ·wall thickness) (p. 217 C).
Thus if, without change in wall thickness, the
ventricular pressure (Pventr) rises (aortic valve
stenosis, hypertension; p.198 and 208)
and/or the ventricular radius increases (greater
filling in mitral or aortic regurgitation;
p.196 and 200), the wall tension necessary
for maintaining normal cardiac output andthus myocardial O2 demand are raised. Should
this continue over a long period, the ventricular
myocardium will hypertrophy (
p. 224ff.). This reduces wall tension, at least
for a while (compensation). Decompensation
occurs when the heart weight has reached the
critical value of 500 g, atwhich time the ventricle
dilates (p. 224ff.). The radius of the
ventricular cavity and thus wall tension increases,
so that O2 demand now suddenly rises
to very high values.
Consequences and symptoms of myocardial
ischemia. The myocardium covers its energy
requirement by metabolizing free fatty acids,
glucose, and lactate. These substrates are used
for the O2-dependent formation of ATP (C,
normal). When blood supply is interrupted
(ischemia), this aerobic energy gain stagnates,
so that ATP can only be formed nonaerobically.
Lactatic acid is now produced, dissociating
into H+ ions and lactate. In these circumstances
not only is lactate not used up, it is actually
produced (C, early “ischemic anoxia”).
The ATP yield is thus quite meagre and, furthermore,
the H+ ions accumulate because of
the interrupted blood flow, both events being
responsible for abnormal ventricular contraction
(reversible cell damage;C). If the ischemia
persists, glycolysis is also inhibited by tissue
acidosis, and irreversible cell damage occurs
(infarct; see below) with release of intracellular
enzymes into the blood (C, left).
ATP deficiency leads to:
! Impairment of the systolic pumping action
of the ventricle (forward failure; p. 224ff.)
as well as
! Decreased compliance of the myocardium
during diastole (backward failure; 
p. 224ff.), so that the diastolic atrial and
ventricular pressures are raised.
! Congestion in the pulmonary circulation
(dyspnea and tachypnea). Just before ventricular
systole the lowered compliance in diastole
produces a fourth heart sound that originates
from the increased atrial contraction
(“atrial gallop”). If the papillary muscles are affected
by the ischemia, this may result in
! Mitral regurgitation (p.196).
! Finally, disorder of myocardial excitation
caused by the ischemia (E) may precipitate
dangerous arrhythmias (ECG;p.186ff.). During
the ischemia period the ECG will show an
elevation or depression (depending on the
lead) of the ST segment as well as flattening
or reversal of the T wave (similar to that in
F4). If the resting ECG of a patient with angina
is normal, these ECG changes can be provoked
by controlled (heart rate, blood pressure)
physical exercise.
Stimulation of the nociceptors (by kinins?,
serotonin?, adenosine?) will lead not only to
– anginal pain (see above), but also to
– generalized activation of the sympathetic
nervous system with tachycardia, sweating,
and nausea.
Therapeutic attempts at restoring an even O2
balance (p. 217 C) in patients with angina
are:
! Lowering myocardial O2 consumption (-
adrenergic blockers; organic nitrates that reduce
the preload [and to some extent also the
afterload] by generalized vasodilation; Ca2+
channel blockers), and
! Increasing the O2 supply (organic nitrate
and Ca2+ channel blockers that both function
to counteract spasm and to dilate coronary
vessels). In addition, the size and position of
the atherosclerotically stenosed coronary arteries
make it possible to dilate them by balloon
angioplasty or vascular stents or by revascularization
with a surgically created aortocoronary
bypass.