580 SECTION VICardiovascular Physiology
skin (see below). Evidence suggests that in the heart it is due to
release of adenosine.
NEURAL FACTORS
The coronary arterioles contain α-adrenergic receptors, which
mediate vasoconstriction, and β-adrenergic receptors, which
mediate vasodilation. Activity in the noradrenergic nerves to
the heart and injections of norepinephrine cause coronary
vasodilation. However, norepinephrine increases the heart rate
and the force of cardiac contraction, and the vasodilation is due
to production of vasodilator metabolites in the myocardium
secondary to the increase in its activity. When the inotropic and
chronotropic effects of noradrenergic discharge are blocked by
a β-adrenergic blocking drug, stimulation of the noradrenergic
nerves or injection of norepinephrine in unanesthetized ani-
mals elicits coronary vasoconstriction. Thus, the direct effect of
noradrenergic stimulation is constriction rather than dilation
of the coronary vessels. On the other hand, stimulation of vagal
fibers to the heart dilates the coronaries.
When the systemic blood pressure falls, the overall effect of
the reflex increase in noradrenergic discharge is increased
coronary blood flow secondary to the metabolic changes in
the myocardium at a time when the cutaneous, renal, and
splanchnic vessels are constricted. In this way the circulation
of the heart, like that of the brain, is preserved when flow to
other organs is compromised.CUTANEOUS CIRCULATION
The amount of heat lost from the body is regulated to a large
extent by varying the amount of blood flowing through the
skin. The fingers, toes, palms, and earlobes contain well-
innervated anastomotic connections between arterioles and
venules (arteriovenous anastomoses; see Chapter 32). Blood
flow in response to thermoregulatory stimuli can vary from 1
to as much as 150 mL/100 g of skin/min, and it has been pos-
tulated that these variations are possible because blood can be
shunted through the anastomoses. The subdermal capillary
and venous plexus is a blood reservoir of some importance,
and the skin is one of the few places where the reactions of
blood vessels can be observed visually.WHITE REACTION
When a pointed object is drawn lightly over the skin, the
stroke lines become pale (white reaction). The mechanical
stimulus apparently initiates contraction of the precapillary
sphincters, and blood drains out of the capillaries and small
veins. The response appears in about 15 s.TRIPLE RESPONSE
When the skin is stroked more firmly with a pointed instru-
ment, instead of the white reaction there is reddening at the site
that appears in about 10 s (red reaction). This is followed in a
few minutes by local swelling and diffuse, mottled reddeningCLINICAL BOX 34–4
Coronary Artery Disease
When flow through a coronary artery is reduced to the point
that the myocardium it supplies becomes hypoxic, angina
pectoris develops (see Chapter 31). If the myocardial is-
chemia is severe and prolonged, irreversible changes occur
in the muscle, and the result is myocardial infarction. Many
individuals have angina only on exertion, and blood flow is
normal at rest. Others have more severe restriction of blood
flow and have anginal pain at rest as well. Partially occluded
coronary arteries can be constricted further by vasospasm,
producing myocardial infarction. However, it is now clear
that the most common cause of myocardial infarction is rup-
ture of an atherosclerotic plaque, or hemorrhage into it,
which triggers the formation of a coronary-occluding clot at
the site of the plaque. The electrocardiographic changes in
myocardial infarction are discussed in Chapter 30. When
myocardial cells actually die, they leak enzymes into the cir-
culation, and measuring the rises in serum enzymes and
isoenzymes produced by infarcted myocardial cells also
plays an important role in the diagnosis of myocardial infarc-
tion. The enzymes most commonly measured today are the
MB isomer of creatine kinase (CK-MB), troponin T, and tropo-
nin I. Myocardial infarction is a very common cause of death
in developed countries because of the widespread occur-
rence of atherosclerosis. In addition, there is a relation be-
tween atherosclerosis and circulating levels of lipopro-
tein(a) (Lp[a]). Lp(a) has an outer coat count of apo(a). It
interferes with fibrinolysis by down-regulating plasmin gen-
eration (see Chapter 32). There is also a strong positive corre-
lation between atherosclerosis and circulating levels of ho-
mocysteine. This substance damages endothelial cells. It is
converted to nontoxic methionine in the presence of folate
and vitamin B 12 , and clinical trials are under way to deter-
mine whether supplements of folate and B 12 lower the inci-
dence of coronary disease. It now appears that atherosclero-
sis has an important inflammatory component as well. The
lesions of the disease contain inflammatory cells, and there is
a positive correlation between increased levels of C-reactive
protein and other inflammatory markers in the circulation
and subsequent myocardial infarction. Treatment of myocar-
dial infarction aims to restore flow to the affected area as
rapidly as possible while minimizing reperfusion injury.
Needless to say, it should be started as promptly as possible
to avoid irreversible changes in heart function.