Biology of Disease

impaired. Stable angina is normally relieved by a short rest or by administering
glyceryltrinitrate. The latter dilates the arteries, increasing blood, and therefore
oxygen, supplies to the muscle leading to less pain.

Variant angina is an intensely painful, transient spasm caused by a blockage of
one of the coronary arteries. It is relatively uncommon, but can occur at rest.
It is exacerbated by smoking and by cocaine use. About one-third of patients
show no evidence of atherosclerotic lesions.

Ischemic heart disease and stable angina can be distinguished from other
conditions that cause chest pain on the basis of their characteristic symptoms
and by a number of types of diagnostic tests, for example the ECG, exercise
stress test and by using coronary angiography to obtain a direct radiographic
visualization, as described earlier.

The management of angina is designed to control the symptoms and reduce
any underlying risk factors. The drugs used include the nitrovasodilators,
for example glyceryltrinitrate, A-adrenoceptor blockers, calcium channel
antagonists, as well as drugs that inhibit platelet aggregation and thrombosis
(Margin Note 14.6 and Chapter 13). In the case of stable angina, mortality is
2 to 4% a year if only one coronary artery is diseased but increases with the
number of diseased arteries.

The other main variant of angina is the so-called unstable angina, which is
a dangerous condition, often heralding an impending myocardial infarction
(Section 14.14). In general, the symptoms resemble those of stable angina
but are more intense and persistent, often lasting 30 min, and the pain is
often resistant to glyceryltrinitrate treatment. The attacks may be frequent,
becoming progressively more severe and prolonged, may be brought on
by minimal exertion (or even during sleep) or may occur several days after
a myocardial infarction. The episodes are preceded by a fall in coronary
blood flow, which is thought to be the result of the periodic development of
coronary thrombosis and vasoconstriction. These are triggered by coronary
arterial disease. The thrombosis may be promoted by the turbulent blood
flow associated with atherosclerotic plaques: there may also be damage to
the endothelial lining of the blood vessels.

An ECG is taken to help in the diagnosis but, in addition, serum levels
of C-reactive protein and amyloid-A protein may be increased; these are
classic markers of inflammation. Unstable angina is a medical emergency
and treatment usually begins with aggressive drug therapy to control the
symptoms and prevent further episodes, and to try to reverse coronary
vasospasm. Platelet glycoproteins IIIA and IIb (Tirofiban and ReoPro) are now
used in unstable angina to stabilize the clot in the narrowed coronary artery,
which is causing the pain, prior to angiography and possibly angioplasty and
stenting. Angioplasty is a procedure similar to angiography (Section 14.5)
but the catheter delivers a small inflatable balloon to the narrowed portion
of the coronary artery. When the balloon is inflated it opens the restricted
section of the artery. Stents are very small, coated spring-like structures
that are deployed, by cardiac catheters into the narrowed section following
angioplasty. They act like miniature struts to maintain the opening of the
vessel.

Urgent revascularization needs to be considered for patients at high risk,
or unsuitable for angioplasty/stenting due to significant coronary arterial
disease. In a coronary artery bypass grafting a length of healthy ‘surplus’ blood
vessel, such as the saphenous vein from the leg (Figure 14.13), is obtained and
pieces of it are inserted between the aorta and the coronary arteries distal to
any stenosis (narrowing). The left internal mammary artery may also be used.
A bypass improves survival in patients with severe atherosclerotic disease in
all the major coronary arteries.

ATHEROSCLEROSIS OR ARTERIOSCLEROSIS

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Margin Note 14.6 Thrombolysis

Thrombolysis is the dissolution of

a blood clot blocking an artery.

Fibrinolysis occurs when the inactive

zymogen, plasminogen, is converted

to the fibrin-dissolving active enzyme

plasmin by endothelium-derived

tissueplasminogen activator (t-PA).

Plasmin also inactivates fibrinogen

and coagulation factors V and VIII

(Chapter 13).

Streptokinase is a bacterial

protein that binds to a molecule

of plasminogen. The resulting

complex cleaves other molecules

of plasminogen to produce more

plasmin, which dissolves the

fibrin. It can cause hemorrhage

and also it can only be used once

since it may cause the patient

to produce antibodies with the

danger of an allergic reaction.

Tissue plasminogen activator is

now produced commercially by

recombinant DNA methods and

marketed as tenecteplase and

alteplase. Tenecteplase is now the

thrombolytic of choice. It binds to

fibrin and this has a greater effect

on clot-associated plasminogen than

on plasma plasminogen. It has the

advantage that it is cleared from

the plasma in a few minutes and is

nonantigenic. Urokinase (u-PA) is

another endogenous plasminogen

activator with properties similar to

those of t-PA.

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