Blood, Heart, and Circulation 439Ischemic Heart Disease
A tissue is said to be ischemic when its oxygen supply is defi-
cient because of inadequate blood flow. The most common
cause of myocardial ischemia is atherosclerosis of the coronary
arteries. The adequacy of blood flow is relative—it depends on
the tissue’s metabolic requirements for oxygen. An obstruction
in a coronary artery, for example, may allow sufficient coro-
nary blood flow at rest but not when the heart is stressed by
exercise or emotional conditions. In these cases, the increased
activity of the sympathoadrenal system causes the heart rate
and blood pressure to rise, increasing the work of the heart and
raising its oxygen requirements. Recent evidence also suggests
that mental stress can cause constriction of atherosclerotic cor-
onary arteries, leading to ischemia of the heart muscle. The
vasoconstriction is believed to result from abnormal function
of a damaged endothelium, which normally prevents constric-
tion (through secretion of paracrine regulators) in response to
mental stress. The control of vasoconstriction and vasodilation
is discussed more fully in chapter 14, section 14.3.
Myocardial ischemia is associated with increased concen-
trations of blood lactic acid produced by anaerobic metabolism
in the ischemic tissue. This condition often causes substernal
pain, which may also be referred to the left shoulder and arm,
as well as to other areas. This referred pain (chapter 10, sec-
tion 10.2) is called angina pectoris. People with angina fre-
quently take nitroglycerin or related drugs that help to relieve
the ischemia and pain. These drugs are effective because they
produce vasodilation, which improves circulation to the heart
and decreases the work that the ventricles must perform to
eject blood into the arteries.
Myocardial cells are adapted for aerobic respiration and
cannot metabolize anaerobically for more than a few minutes.
If ischemia and anaerobic metabolism are prolonged, necro-
sis (cellular death) may occur in the areas most deprived of
oxygen. A sudden, irreversible injury of this kind is called a
myocardial infarction, or MI. Often called “heart attack”
(though this imprecise term may also refer to other condi-
tions), myocardial infarction is the leading cause of death in
the Western world.
The area of dead cells is not replaced because human myo-
cardial cells have only a very limited capacity to divide. Instead,
fibroblasts produce noncontractile scar tissue, which forms the
infarct. The area of infarcted tissue is usually relatively small
if the person is hospitalized and treated within a few hours
after the onset of symptoms. However, after the heart becomes
re-perfused with blood (so that it receives sufficient oxygen
to resume aerobic respiration), larger numbers of myocardial
cells may die. This reperfusion injury may be a greater threat
than the initial event and is caused by apoptosis (chapter 3,
section 3.5) due to the accumulation of Ca^2 1 and the produc-
tion of superoxide free radicals (chapters 5 and 19) by mito-
chondria. Apoptosis of myocardial cells surrounding the initial
lesion can greatly increase the size of the infarct and weaken
the wall of the ventricle.
The infarct may thereby cause the ventricular wall to thin
and distend under pressure. In recent years, scientists have inves-
tigated a variety of potential stem cell therapies for myocardial
infarction. These include the use of stem cells from the bone
marrow (which can secrete cytokines that promote healing); the
possible differentiation of embryonic stem cells and induced
pluripotent stem cells (chapter 20, section 20.6) into myocar-
dial cells; and the transformation of fibroblasts (perhaps within
an infarct) into myocardial cells. Another approach has been to
stimulate myocardial cell division, which is normally too limited
to repair the infarct. This has been achieved in rodent hearts , but
more research in these strategies, particularly involving human
hearts, is needed before they can become medical therapies.
Acute chest pain caused by myocardial ischemia is a com-
mon reason that patients seek emergency medical care. Myocar-
dial ischemia may be detected by changes in the S-T segment
of the electrocardiogram ( fig. 13.33 ). Sustained occlusion of a
coronary artery that produces a myocardial infarction (MI) is
accompanied by an elevation of the S-T segment of the ECG.
Chest pain from myocardial ischemia can indicate the pres-
ence of myocardial infarction (MI), and early detection of an
MI is very important. Currently, the diagnosis of an MI is based
mainly on rising blood troponin levels, primarily troponin I.
Troponin is a regulatory protein in muscles (chapter 12, sec-
tion 12.2) released into the blood from damaged myocardial
cells. Tests for enzymes released into the blood from damaged
myocardial cells are also useful. These include tests for creatine
phosphokinase (CPK) and lactate dehydrogenase (LDH). Once
an MI has been detected and the patient is stabilized, the rea-
son for the myocardial ischemia can be addressed. The detec-
tion and treatment of coronary thrombosis is discussed with the
coronary circulation in chapter 14, section 14.4 (see fig. 14.18).FITNESS APPLICATION
Exercise and a proper diet contribute to cardiovascular
health. The American Heart Association ( AHA ) recommends
that people exercise moderately for at least 30 minutes
on most days, and even better, engage in 40 minutes of
aerobic exercise 3 to 4 times a week. People should eat
a diet that encompasses all food groups and contains low
amounts of high-calorie/low-nutrient items. To achieve the
goal of lowering blood cholesterol, saturated fat and trans
fats should be limited to 5% to 6% of total calories. By
contrast, 40% to 50% of the calories in many typical fast-
food meals are derived from fat. The AHA recommends that
people eat fish at least twice a week. One of the benefits of
this is that fish—especially oily fish such as trout, salmon,
mackerel, herring, and sardines—are rich in omega-3 (or
n-3) fatty acids, which appear to provide some protection
against cardiovascular disease. Walnuts, soybeans, and
rapeseed (canola) oil are also rich in EPA and DHA, the n-3
fatty acids found in fish (chapter 19, section 19.1). However,
the singly most effective action that smokers can take to
lower their risk of atherosclerosis is to stop smoking.