Chapter 12: Ischemic Heart Disease

Question 1

What is MI?

Answer 1

myocardial ischemia—an imbalance between the supply (perfusion) and demand of the heart for oxygenated blood.

Ischemia brings not only an
insufficiency of oxygen, but also reduces the availability of nutrients and the removal of
metabolites ( Chapter 1 ).

For this reason, ischemia is generally less well tolerated by the heart than pure hypoxia, such as may be seen with severe anemia, cyanotic heart disease, or
advanced lung disease

Question 2

What is IHD?

Answer 2

IHD is the generic designation for a group of pathophysiologically
related syndromes resulting from myocardial ischemia—an imbalance between the supply
(perfusion) and demand of the heart for oxygenated blood.

Ischemia brings not only an
insufficiency of oxygen, but also reduces the availability of nutrients and the removal of
metabolites ( Chapter 1 ).

For this reason, ischemia is generally less well tolerated by the heart
than pure hypoxia, such as may be seen with severe anemia, cyanotic heart disease, or
advanced lung disease

Question 3

What is the reason why ischemia is generally less well tolerated by the heart than pure hypoxis?

Answer 3

Ischemia brings not only an
insufficiency of oxygen, but also reduces the availability of nutrients and the removal of
metabolites ( Chapter 1 ).

For this reason, ischemia is generally less well tolerated by the heart than pure hypoxia, such as may be seen with severe anemia, cyanotic heart disease, or
advanced lung disease

Question 4

In more than 90% of cases, the cause of myocardial ischemia is what?

Answer 4

In more than 90% of cases, the cause of myocardial ischemia is reduced blood flow due to
obstructive atherosclerotic lesions in the coronary arteries.

Question 5

IHD is often termed coronary artery disease ( CAD).

T or F

Answer 5

True

In more than 90% of cases, the cause of myocardial ischemia is reduced blood flow due to
obstructive atherosclerotic lesions in the coronary arteries.

Thus, **IHD is often termed coronary
artery disease (CAD) or coronary heart disease.**

In most cases there is a long period (up to
decades) of silent, slow progression of coronary lesions before symptoms appear. Thus, the
syndromes of IHD are only the late manifestations of coronary atherosclerosis that may have
started during childhood or adolescence ( Chapter 11 ).

Question 6

Is it true that the symptoms of IHD is on the late clinical manifestations ?

T or F

Answer 6

In most cases there is a long period (up to
decades) of silent, slow progression of coronary lesions before symptoms appear.

Thus, the
syndromes of IHD are only the late manifestations of coronary atherosclerosis that may have
started during childhood or adolescence ( Chapter 11 ).

Question 7

IHD usually presents as one or more of the following clinical syndromes:

Answer 7

• Myocardial infarction, the most important form of IHD, in which ischemia causes the death of heart muscle.
• Angina pectoris, in which the ischemia is of insufficient severity to cause infarction, but may be a harbinger of MI.
• Chronic IHD with heart failure.
• Sudden cardiac death

Question 8

What is the most important form of IHD, in which ischemia causes the
death of heart muscle.

Answer 8

Myocardial infarction

Question 9

What is Angina perctoris?

Answer 9

• *Angina pectoris**, in which the ischemia is of insufficient severity to cause infarction, but
• may be a harbinger of MI.*

Question 10

In addition to coronary atherosclerosis, myocardial ischemia may be caused by what?

Answer 10

• coronary emboli,
• blockage of small myocardial blood vessels, and
• lowered systemic blood pressure (e.g., shock).

Question 11

Moreover, in the setting of coronary arterial obstruction, ischemia can be aggravated by
what?

Answer 11

• an increase in cardiac energy demand (e.g., as occurs with myocardial hypertrophy or
• increased heart rate [tachycardia]), by diminished availability of blood or oxygen due to shock,
• or by hypoxemia.

Question 12

Why are some conditions like tachycardia have deleterious effects in IHD?

Answer 12

Some conditions have several deleterious effects; for example, tachycardia increases oxygen demand (because of more contractions per unit time) and decreases supply
(by decreasing the relative time spent in diastole, when cardiac perfusion occurs).

Question 13

Since its peak in 1963, the overall death rate from IHD has fallen in the United States by approximately 50%.

This remarkable improvement has resulted primarily
from:

Answer 13

(1) prevention, achieved by modification of important risk factors, such as smoking, elevated blood cholesterol, and hypertension, and

(2) diagnostic and therapeutic advances,
allowing earlier, more effective, and safer treatments.

Question 14

What are the new therapy that decreases the incidence of IHD?

Answer 14

The latter include new medications,
coronary care units, thrombolysis for MI, percutaneous transluminal coronary angioplasty, endovascular stents, coronary artery bypass graft (CABG) surgery, andimproved control of
heart failure and arrhythmias

Question 15

What are the additional risk reduction can be done in IHD?

Answer 15

Additional risk reduction may potentially be achieved by maintenance of normal blood glucose levels in diabetic patients, control of obesity, and
prophylactic anticoagulation of middle-aged men with aspirin.

Nevertheless, continuing this
encouraging trend in the 21st century will be challenging, in view of the predicted doubling of
the number of individuals over age 65 by 2050 and the increased longevity of “baby boomers,”
the “obesity epidemic,” and other factors.

Interestingly, the genetic determinants of coronary
atherosclerosis and IHD may not be identical, since MI occurs in only a small fraction of
individuals with coronary disease.

For example, the risk of MI but not coronary atherosclerosis is associated with genetic variants that modify leukotriene B4 metabolism

Question 16

Pathogenesis of IHD.

Answer 16

The dominant cause of the IHD syndromes is insufficient coronary perfusion relative to
myocardial demand, due to chronic, progressive atherosclerotic narrowing of the epicardial
coronary arteries, andvariable degrees of superimposed acute plaque change, thrombosis,
and vasospasm. The individual elements and their interactions are discussed be

Question 17

The individual elements of IHD and their interactions are:

Answer 17

• Chronic Atherosclerosis.
• Acute Plaque Change
• Consequences of Myocardial Ischemia.

Question 18

What is with IHD that 90% of patients have?

Answer 18

More than 90% of patients with IHD have atherosclerosis of one or more of the epicardial
coronary arteries.

Question 19

The clinical manifestations of coronary atherosclerosis are due to what?

Answer 19

The clinical manifestations of coronary atherosclerosis are generally due to progressive narrowing of the lumen leading to stenosis (“fixed” obstructions) or to acute plaque disruption with thrombosis, both of which compromise blood flow.

Question 20

What percent of obstruction is generally required to cause symptomatic ischemia precipitated by exercise?

Answer 20

A fixed lesion obstructing 75%
or greater of the lumen is generally required to cause symptomatic ischemia precipitated by
exercise (most often manifested as chest pain, known as angina); with this degree of
obstruction, compensatory coronary arterial vasodilation is no longer sufficient to meet even
moderate increases in myocardial demand.

Question 21

What is Angina?

Answer 21

symptomatic ischemia precipitated by
exercise (most often manifested as chest pain,known as angina);

Question 22

What percent of obstruction can lead to inadequate coronary blood flow even at rest?

Answer 22

Obstruction of 90% of the lumen can lead to
inadequate coronary blood flow even at rest.

Question 23

When progressive myocardial ischemia induced by
slowly developing occlusions it may stimulate what in which can protect against myocardial ischemia?

Answer 23

The progressive myocardial ischemia induced by
slowly developing occlusions may stimulate the formation of collateral vessels over time, which
can protect against myocardial ischemia and infarction and mitigate the effects of high-grade
stenoses

Question 24

Although only a single major coronoray epicardial trunk may be affected, two or all three are often involved by atherosclerosis which are?

Answer 24

Although only a single major coronary epicardial trunk may be affected, two or all three—

• the left anterior descending (LAD),
• the left circumflex (LCX),
• and the right coronary artery (RCA)—

are often involved by atherosclerosis.

Question 25

Clinically significant stenosing plaques may be located
anywhere within these vessels but tend to predominate where?

Answer 25

Clinically significant stenosing plaques may be located
anywhere within these vessels but tend to predominate within the first several centimeters of the LAD and LCX and along the entire length of the RCA.

Question 26

Sometimes the major secondary
epicardial branches are also involved such as what?,

Answer 26

Sometimes the major secondary
epicardial branches are also involved

• diagonal branches of the LAD,
• obtuse marginal branches of the LCX, or
• posterior descending branch of the RCA)

Question 27

Atherosclerosis can also affect the intramural ( penetrating ) branches.

T or F

Answer 27

True

but atherosclerosis of the
intramural (penetrating) branches is rare.

Question 28

The risk of an individual developing clinically important IHD depends in part on the what?

Answer 28

• number,
• distribution
• structure, and
• degree of obstruction of atheromatous plaques.

Question 29

However, the varied
clinical manifestations of IHD cannot be explained by the anatomic disease burden alone with the following syndromes :

Answer 29

This
is particularly true for the so-called acute coronary syndromes, unstable angina, acute MI, and
sudden death.

Question 30

What are ACUTE CORONARY SYNDROMES?

Answer 30

The acute coronary syndromes are typically initiated by an unpredictable and
abrupt conversion of a stable atherosclerotic plaque to an unstable and potentially lifethreatening
atherothrombotic lesion through rupture, superficial erosion, ulceration, fissuring, or
deep hemorrhage( Chapter 11 ).

Question 31

In most instances, the plaque change causes what?

Answer 31

In most instances, the plaque change causes the formation of a superimposed thrombus that partially or completely occludes the affected artery. [46] [47]

These acute events are often associated with intralesional inflammation, which you will
remember mediates the initiation, progression, and acute complications of atherosclerosis
(discussed in Chapter 11 )

. For purposes of simplicity, the spectrum of acute alterations in
atherosclerotic lesions will be termed either plaque disruption or plaque change.

Question 32

In each syndrome the critical consequence is downstream myocardial ischemia

Answer 32

• Stable angina
• Unstable angina
• MI
• sudden cardiac death

Question 33

What is stable angina?

Answer 33

Stable angina results from increases in myocardial oxygen demand that outstrip the ability of stenosed
coronary arteries to increase oxygen delivery; it is usually not associated with plaque disruption.

Question 34

What is unstable angina?

Answer 34

Unstable angina is caused by plaque rupture complicated by partially occlusive thrombosis and
vasoconstriction, which lead to severe but transient reductions in coronary blood flow. In some
cases, microinfarcts can occur distal to disrupted plaques due to thromboemboli.

Question 35

In MI, acute
plaque change induces what?

Answer 35

In MI, acute
plaque change induces total thrombotic occlusion and the subsequent death of heart muscle.

Question 36

What is sudden cardiac death?

Answer 36

Finally, sudden cardiac death frequently involves an atherosclerotic lesion in which a disrupted
plaque causes regional myocardial ischemia that induces a fatal ventricular arrhythmia.

Each of
these important syndromes is discussed in detail below, followed by an examination of the
important myocardial consequences.

Question 37

What is Angina pectoris?

Answer 37

Angina pectoris (literally, chest pain)

Question 38

Answer 38

FIGURE 12-9 Schematic of sequential progression of coronary artery lesions and their
association with various acute coronary syndromes.

Question 39

What is the characteristic of angina pectoris?

Answer 39

is characterized by paroxysmal (sudden recurrence) and usually recurrent
attacks of substernalorprecordial chestdiscomfort (variously described asconstricting,
squeezing, choking, or knifelike)caused bytransient (15 seconds to 15 minutes) myocardial
ischemia that falls short of inducing myocyte necrosis

Question 40

What are the three overlapping patterns of angina pectoris?

Answer 40

The three overlapping patterns of angina pectoris—

• (1) stable or typical angina,
• (2) Prinzmetal variant angina, and
• (3) unstable or crescendo angina—

are caused by varying combinations of increased myocardial demand, decreased myocardial perfusion, and coronary arterial pathology.

Question 41

All ischemic events are perceived by patients?

T or F

Answer 41

FALSE

Moreover, not all ischemic events are perceived by patients (silent ischemia).

Question 42

What is stable angina?

Answer 42

Stable angina, the most common form, is also called typical angina pectoris.

It is caused by an
imbalance in coronary perfusion (due to chronic stenosing coronary atherosclerosis) relative to
myocardial demand, such as that produced by physical activity, emotional excitement, or any
other cause of increased cardiac workload.

Typical angina pectoris is usually relieved by rest
(which decreases demand) or administering nitroglycerin, a strong vasodilator (which increases
perfusion)

Question 43

Is Typical angina usually relieved by rest or adminesteration of nitroglycerin?

T or F

Answer 43

True

Typical angina pectoris is usually relieved by rest
(which decreases demand) or administering nitroglycerin, a strong vasodilator (which increases
perfusion)

Question 44

What is Prinzmetal variant angina?

Answer 44

Prinzmetal variant angina is an uncommon from of episodic myocardial ischemia that is caused
by coronary artery spasm.

Although individuals with Prinzmetal variant angina may well have significant coronary atherosclerosis, the anginal attacks are unrelated to physical activity, heart
rate, or blood pressure.

Prinzmetal angina generally responds promptly to vasodilators, such as
nitroglycerin and calcium channel blockers.

Question 45

Prinzmetal variant angina are unrelated to physical activity, heart
rate, or blood pressure.

T or F

Answer 45

True

Although individuals with Prinzmetal variant angina may well have significant coronary atherosclerosis, the anginal attacks are unrelated to physical activity, heart
rate, or blood pressure.

Prinzmetal angina generally responds promptly to vasodilators, such as
nitroglycerin and calcium channel blockers.

Question 46

Prinzmetal angina generally responds to what?

Answer 46

Prinzmetal angina generally responds promptly to vasodilators, such as
nitroglycerin and calcium channel blockers.

Question 47

What is unstable or crescendo angina?

Answer 47

Unstable or crescendo angina refers to a pattern of increasingly frequent pain, often of
prolonged duration,that isprecipitated by progressively lower levels of physical activity or that
even occurs at rest.

Question 48

In most patients what is the cause of unstable angina?

Answer 48

In most patients, unstable angina is caused by the disruption of an
atherosclerotic plaquewithsuperimposed partial (mural) thrombosisandpossibly embolization
or vasospasm (or both).

Unstable angina thus serves as a warning that an acute MI may be imminent; indeed, this syndrome is sometimes referred to as preinfarction angina

Question 49

What is the other term for unstable angina?

Answer 49

Unstable angina thus serves as a warning that an acute MI may be imminent; indeed, this syndrome is sometimes referred to as preinfarction angina

Question 50

What is MI?

Answer 50

MI, also known as “heart attack,” is the death of cardiac muscle due to prolonged severe
ischemia.

It is by far the most important form of IHD.

About 1.5 million individuals in the United
States suffer an MI annually.

Question 51

What age are affected by MI?

Answer 51

MI can occur at virtually any age, but its frequency rises progressively with increasing age and
when predispositions to atherosclerosis are present

Question 52

How many percent of MI occurs in 40 yo?

Answer 52

Nearly 10% of myocardial infarcts occur in
people under age 40,

Question 53

How many percent of MI occurs in 65 yo and above?

Answer 53

and 45% occur in people under age 65.

Question 54

Whites are greatly
affected by MI

T or F

Answer 54

FALSE

Blacks and whites are equally
affected.

Question 55

Throughout life, men and women are equally affected by MI

T or F

Answer 55

FALSE

Throughout life, men are at significantly greater risk than women.

Indeed, except

• *for those having some predisposing atherogenic condition**, women are protected against MI and
• *other heart diseases** during the reproductive years.

However, the decrease of estrogen
following menopause is associated with rapid development of CAD, and IHD is the most
common cause of death in elderly women. Postmenopausal hormonal replacement therapy is
not currently felt to protect against atherosclerosis and IHD ( Chapter 11 ).

Question 56

Why are women of those who are at reproductive years are protected from MI except for those who are predisposing atherogenic condition?

Answer 56

Indeed, except for those having some predisposing atherogenic condition, women are protected against MI and other heart diseases during the reproductive years.

However, the decrease of estrogen
following menopause is associated with rapid development of CAD, andIHD is the most
common cause of death in elderly women.

Postmenopausal hormonal replacement therapy is
not currently felt to protect against atherosclerosis and IHD ( Chapter 11 ).

Question 57

Pathogenesis.
We now consider the basis for and consequences of myocardial ischemia.

Answer 57

• Coronary Arterial Occlusion
• Myocardial Response.
• Transmural Versus Subendocardial Infarction
• Infarct Modification by Reperfusion.

Question 58

In the typical case of MI, the following sequence of events is considered most likely (see
Chapter 11 for more detail):

Answer 58

• sudden change in atheromatous plaque
• platelet activation due to endotheilal exposure to collagen
• Vasospasm from mediators released by platelets
• Coagulation pathway activated
• **Frequently within minutes, the thrombus evolves to completely occlude the lumen of the
  vessel. **

Question 59

What is the initial event in Coronary Arterial Occlusion.?

Answer 59

The initial event is a sudden change in an atheromatous plaque, which may consist of
intraplaque hemorrhage, erosion or ulceration, or rupture or fissuring.

Question 60

The initial event is a sudden change in an atheromatous plaque, which may consist of

Answer 60

• intraplaque hemorrhage,
• erosion or ulceration, or
• rupture or fissuring.

Question 61

What happens when exposed to subendothelial collagen and necrotic plaque contents?

Answer 61

• ,platelets adhere,
• become activated,
• release their granule contents,
• and aggregate to form microthrombi.

Question 62

What stimulates Vasospasm ?

Answer 62

Vasospasm is stimulated by mediators released from platelets.

Question 63

What adds to the bulk of the thrombus?

Answer 63

Tissue factor activates the coagulation pathway, adding to the bulk of the thrombus.

Question 64

How long does it take in the events of Coronary Arterial Occlusion will the thrombus completely occlude the lumen of the vessel?

Answer 64

Frequently within minutes, the thrombus evolves to completely occlude the lumen of the
vessel.

Question 65

Compelling evidence for the coronary occlusion sequence has been obtained from :

Answer 65

Compelling evidence for this sequence has been obtained from

• (1) autopsy studies of patients dying of acute MI,
• (2) angiographic studies demonstrating a high frequency of thrombotic occlusion early after MI
• (3) the high success rate of coronary revascularization (i.e., thrombolysis, angioplasty, stent placement, and surgery) following MI, and
• (4) the demonstration of residual disrupted atherosclerotic lesions by angiography after thrombolysis.

Question 66

In 90% of cases what is seen in a coronary angiography when it is performed within 4 hours?

Answer 66

Coronary angiography performed within 4 hours of the onset of an MI shows a thrombosed
coronary artery in almost 90% of cases.

Question 67

However, when angiography is delayed until 12 to 24

ours after onset, how many percent of occlusion is see?

Answer 67

However, when angiography is delayed until 12 to 24

hours after onset, occlusion is seen only about 60% of the time, suggesting that some occlusions resolve due to fibrinolysis, relaxation of spasm, or both.

Question 68

In approximately 10% of cases, transmural MI occurs in the absence of the typical coronary
vascular pathology.

In such situations, other mechanisms may be responsible for the reduced
coronary blood flow, including:

Answer 68

• Vasospasm with or without coronary atherosclerosis
• Emboli
• Ischemia

Question 69

In approximately 10% of cases, transmural MI occurs in the absence of the typical coronary
vascular pathology.

In such situations, other mechanisms may be responsible for the reduced
coronary blood flow, including: vasospasm, what is the reason?

Answer 69

Vasospasm with or without coronary atherosclerosis, perhaps in association with platelet
aggregation or due to cocaine abuse

Question 70

In approximately 10% of cases, transmural MI occurs in the absence of the typical coronary
vascular pathology.

In such situations, other mechanisms may be responsible for the reduced
coronary blood flow, including: Emboli comes from where?

Answer 70

• Emboli from the left atrium in association with atrial fibrillation, a left-sided mural thrombus, vegetations of infective endocarditis, intracardiac prosthetic material; or
• paradoxical emboli from the right side of the heart or the peripheral veins, which travel through a patent foramen ovale to the coronary arteries

Question 71

In approximately 10% of cases, transmural MI occurs in the absence of the typical coronary
vascular pathology.

In such situations, other mechanisms may be responsible for the reduced
coronary blood flow, including: Ischemia without detectable coronary atherosclerosis and thrombosis may be caused by what?

Answer 71

by disorders of small intramural coronary vessels, such as:

• vasculitis,
• hematologic abnormalities such as sickle cell disease,
• amyloid deposition in vascular walls, and
• vascular dissection;
• lowered systemic blood pressure (shock); or
• inadequate myocardial “protection” during cardiac surgery

Question 72

What is the area of risk?

Answer 72

Coronary arterial obstruction compromises the blood supply to a region of myocardium ( Fig.
12-10 ), causing ischemia, myocardial dysfunction, and potentially myocyte death.

The anatomic region supplied by that artery is referred to as the area at risk . The outcome depends
predominantly on the severity and duration of flow deprivation ( Fig. 12-11 ).

Question 73

Answer 73

FIGURE 12-10 Postmortem angiogram showing the posterior aspect of the heart of a
patient who died during the evolution of acute myocardial infarction, demonstrating total
occlusion of the distal right coronary arteryby anacute thrombus (arrow) and alarge zone
of myocardial hypoperfusion involving the posterior left and right ventricles, as indicated by
arrowheads, and having almost absent filling of capillaries.

The heart has been fixed by
coronary arterial perfusion with glutaraldehyde and cleared with methyl salicylate, followed
by intracoronary injection of silicone polymer (yellow). Photograph courtesy of Lewis L.
Lainey.

Question 74

Answer 74

FIGURE 12-11 Temporal sequence of early biochemical findings and progression of
necrosis after onset of severe myocardial ischemia.

• A, Early changes include loss of adenosine triphosphate (ATP) and accumulation of lactate
• B, For approximately 30 minutes after the onset of even the most severe ischemia, myocardial injury is potentially reversible. Thereafter, progressive loss of viability occurs that is complete by 6 to 12 hours. The benefits of reperfusion are greatest when it is achieved early, and are progressively lost when reperfusion is delayed.

Question 75

Temporal sequence of early biochemical findings and progression of
necrosis after onset of severe myocardial ischemia.

Answer 75

• A, Early changes include loss of adenosine triphosphate (ATP) and accumulation of lactate.
• B, For approximately 30 minutes after the onset of even the most severe ischemia, myocardial injury is potentially reversible. Thereafter, progressive loss of viability occurs that is complete by 6 to 12 hours. The benefits of reperfusion are greatest when it is achieved early, and are progressively lost when reperfusion is delayed.

Question 76

What are the early biochemical consequence of myocardial ischemia?

Answer 76

The early biochemical consequence of myocardial ischemia is the cessation of aerobic
metabolism within seconds, leading toinadequate production of high-energy phosphates (e.g.,
creatine phosphate and adenosine triphosphate) and accumulation of potentially noxious
metabolites (such as lactic acid) ( Fig. 12-11A ).

Question 77

Because of the exquisite dependence of
myocardial function on oxygen, severe ischemia induces loss of contractility within how long?

Answer 77

60 seconds.

This cessation of function can precipitate acute heart failure long before myocardial cell death.
As detailed in Chapter 1 , ultrastructural changes (including myofibrillar relaxation, glycogen
depletion, cell and mitochondrial swelling) also develop within a few minutes of the onset of
ischemia.

Nevertheless, these early changes are potentially reversible.

Question 78

As demonstrated both
experimentally and in clinical studies, only severe ischemia lasting 20 to 30 minutes or longer
leads to irreversible damage (necrosis) of cardiac myocytes.

Question 79

Ultrastructural evidence of
irreversible myocyte injury(primary structural defects in the sarcolemmal membrane) develops
only after prolonged, severe myocardial ischemia (such as occurs when blood flow is_______________)

Answer 79

10% or
less of normal).

Question 80

What is the key feature that marks the early phases of myocyte necrosis?

Answer 80

A key feature that marks the early phases of myocyte necrosis is the disruption of the integrity
of the sarcolemmal membrane, which allowsintracellular macromolecules to leak out of cells
into the cardiac interstitiumandultimately into the microvasculature and lymphatics in the
region of the infarct.

Question 81

Tests that measure the levels of myocardial proteins in the blood are important in the diagnosis and management of MI (see later).

With prolonged severe ischemia, injury to the microvasculature then follows.

The temporal progression of these events is
summarized in Table 12-4

Question 82

TABLE 12-4 – Approximate Time of Onset of Key Events in Ischemic Cardiac Myocytes

Answer 82

Feature :Time

• Onset of ATP depletion: Seconds
• Loss of contractility :<2 min
• ATP reduced
  
  • to 50% of normal : 10 min
  • to 10% of normal: 40 min
• Irreversible cell injury: 20–40 min
• Microvascular injury : >1 hr

Question 83

In most cases of acute MI, permanent damage to the heart occurs when the perfusion of the
myocardium is severely reduced for an extended interval usually for how long?

Answer 83

(usually at least 2 to 4 hours), ( Fig.
12-11B ).

This delay in the onset of permanent myocardial injury provides the rationale for rapid diagnosis in acute MI—to permit early coronary intervention, the purpose of which is to
establish reperfusion and salvage as much “at risk” myocardium as possible

Question 84

The progression of ischemic necrosis in the myocardium is summarized in Figure 12-12 .

Ischemia is most pronounced in the ____; thus, irreversible injury of ischemic myocytes occurs first in the subendocardial zone.

Answer 84

subendocardium

Question 85

Ischemia is most pronounced in the subendocardium; thus, irreversible injury of ischemic myocytes occurs first where?

Answer 85

in the subendocardial zone.

Question 86

With more extended ischemia, a wavefront of
cell death moves through the myocardium to involve progressively more of the transmural
thickness and breadth of the ischemic zone.

The precise location, size, and specific
morphologic features of an acute MI depend on:

Answer 86

• The location, severity, and rate of development of coronary obstructions due to atherosclerosis and thromboses
• • The size of the vascular bed perfused by the obstructed vessels
• • The duration of the occlusion
• • The metabolic/oxygen needs of the myocardium at risk
• • The extent of collateral blood vessels
• • The presence, site, and severity of coronary arterial spasm
• • Other factors, such as heart rate, cardiac rhythm, and blood oxygenation

Question 87

Answer 87

FIGURE 12-12 Progression of myocardial necrosis after coronary artery occlusion.

• Necrosis begins in a small zone of the myocardium beneath the endocardial surface in the center of the ischemic zone.
• The area that depends on the occluded vessel for perfusion is the “at risk” myocardium (shaded).
• Note that a very narrow zone of myocardium immediately beneath the endocardium is spared from necrosis because it can be oxygenated by diffusion from the ventricle.

Question 88

When is necrosis usually complete?

Answer 88

Necrosis is usually complete within 6 hours of the onset of severe myocardial ischemia.

However, in instances where the coronary arterial collateral system, stimulated by chronic ischemia,
is better developed and thereby more effective, the progression of necrosis may follow a more protracted course (possibly over 12 hours or longer)

Question 89

Knowledge of the areas of myocardium perfused by the three major coronary arteries helps
correlate sites of vascular obstruction with regions of myocardial infarction.

Typically, the left
anterior descending branchof theleft coronary artery (LAD) supplies most of the :

Answer 89

• apex of the heart (distal end of the ventricles),
• the anterior wall of the left ventricle, and the anterior two thirds of the ventricular septum.

Question 90

What coronary artery is called the dominant?

Answer 90

By convention, the coronary artery (either the right coronary artery [RCA] or the left circumflex artery [LCX]) that perfuses the posterior third of the septum is
called “dominant” (even though the LAD and LCX collectively perfuse the majority of the left
ventricular myocardium).

Question 91

What is the reason when there are occlusions of the RCA ( as well as left coronary artery) can cause left ventricular damage?

Answer 91

In a right dominant circulation, present in approximately four fifths of
individuals,theLCX generally perfuses only the lateral wall of the left ventricle, and theRCA
supplies the entire right ventricular free wall,theposterobasal wall of the left ventricle, and the
posterior third of the ventricular septum.

Thus, occlusions of the RCA (as well as the left
coronary artery) can cause left ventricular damage. The right and left coronary arteries function
as end arteries, aright and left coronary arteries function as end arteries, although anatomically most hearts have numerous intercoronary anastomoses (connections called the collateral circulation). Little blood courses through the collateral
circulation in the normal heart. However, when one artery is severely narrowed, blood flows via
collaterals from the high- to the low-pressure system, and causes the channels to enlarge.
Thus, progressive dilation and growth of collaterals, stimulated by ischemia, may play a role in
providing blood flow to areas of the myocardium otherwise deprived of adequate perfusion.

Question 92

The distribution of myocardial necrosis correlates with what?

Answer 92

the location and cause of the decreased
perfusion ( Fig. 12-16 ).

Question 93

Most myocardial infarcts are of what type?

Answer 93

​Most myocardial infarcts are transmural, in which the ischemic necrosis
involves the full or nearly full thickness of the ventricular wall in the distribution of a single
coronary artery. This pattern of infarction is usually associated with a combination of chronic
coronary atherosclerosis, acute plaque change, and superimposed thrombosis (as discussed
previously).

Question 94

What are transmural myocardial infarct?

Answer 94

​Most myocardial infarcts are transmural, in which the ischemic necrosis involves the full or nearly full thickness of the ventricular wall in the distribution of a single coronary artery.

​Most myocardial infarcts are transmural, in which the ischemic necrosis
involves the full or nearly full thickness of the ventricular wall in the distribution of a single
coronary artery. This pattern of infarction is usually associated with a combination of chronic
coronary atherosclerosis, acute plaque change, and superimposed thrombosis (as discussed
previously).

Question 95

​Most myocardial infarcts are transmural, in which the ischemic necrosis
involves the full or nearly full thickness of the ventricular wall in the distribution of a single
coronary artery. This pattern of infarction is usually associated with a combination of what?

Answer 95

• chronic coronary atherosclerosis,
• acute plaque change,
• and superimposed thrombosis (as discussed previously).

Question 96

What is subendocardial ( nontransmural) infarct?

Answer 96

In contrast, a subendocardial (nontransmural) infarct constitutes an area of ischemic necrosis limited to the inner one third to one half of the ventricular wall.

As the
subendocardial zone is normally the least perfused region of myocardium, this area is most
vulnerable to any reduction in coronary flow.

Question 97

A subendocardial infarct can occur as a result of a
what?

Answer 97

plaque disruption followed by a coronary thrombus that becomes lysed before myocardial
necrosis extends across the full thickness of the wall; in this case theinfarct will be limited to the
distribution of the coronary artery that suffered plaque change.

However, subendocardial
infarcts can also result from prolonged, severe reduction in systemic blood pressure, as in
shock superimposed on chronic, otherwise noncritical, coronary stenoses.

In the
subendocardial infarcts that occur as a result of global hypotension, myocardial damage is usually circumferential, rather than being limited to the distribution of a single major coronary
artery. Owing to the characteristic electrocardiographic changes resulting from myocardial
ischemia/necrosis in various distributions, transmural infarcts are often referred to as “ST
elevation infarcts” and subendocardial infarcts are known as “non-ST elevation infarcts.”

Question 98

In the
subendocardial infarcts that occur as a result of global hypotension, myocardial damage is
usually what?

Answer 98

• *circumferential**, **rather than being limited to the distribution of a single major coronary
  artery. **

Question 99

Owing to the characteristic electrocardiographic changes resulting from myocardial
ischemia/necrosis in various distributions, transmural infarcts are often referred to as___________

Answer 99

“ST
elevation infarcts”

Question 100

Owing to the characteristic electrocardiographic changes resulting from myocardial
ischemia/necrosis in various distributions,subendocardial infarcts are known as ____________

Answer 100

“non-ST elevation infarcts.”

Question 101

Answer 101

FIGURE 12-16 Consequences of myocardial ischemia followed by reperfusion.

• A, Schematic illustration of the progression of myocardial ischemic injury and its modification by restoration of flow (reperfusion). Hearts suffering brief periods of ischemia of longer than 20 minutes followed by reperfusion do not develop necrosis (reversible injury). Brief ischemia followed by reperfusion results in stunning. If coronary occlusion is extended beyond 20 minutes’ duration, a wavefront of necrosis progresses from subendocardium to subepicardium over time. Reperfusion before 3 to 6 hours of ischemia salvages ischemic but viable tissue. This salvaged tissue may also demonstrate stunning. Reperfusion beyond 6 hours does not appreciably reduce myocardial infarct size.
• B, Gross and
• C, microscopic appearance of myocardium modified by reperfusion.
• B, Large, densely hemorrhagic, anterior wall acute myocardial infarction in a patient with left anterior descending artery thrombus treated with streptokinase, a fibrinolytic agent (triphenyl tetrazolium chloride–stained heart slice). Specimen oriented with posterior wall at top.
• C, Myocardial necrosis with hemorrhage and contraction bands, visible as dark bands spanning some myofibers (arrow). This is the characteristic appearance of markedly ischemic myocardium that has been reperfused.

Question 102

TABLE 12-5 – Evolution of Morphologic Changes in Myocardial Infarction

REVERSIBLE INJURY

Answer 102

Time: 0–½ hr

Gross Features:None

Light Microscope :None

Electron Microscope: Ralaxation of myofibrils; glycogen loss; mitochondrial swelling

Question 103

TABLE 12-5 – Evolution of Morphologic Changes in Myocardial Infarction

IRREVERSIBLE INJURY

Answer 103

• Time : ½–4 hr
• Gross Features : None
• Light Microscope: Usually none; variable waviness of fibers at border
• Electron Microscope: Sarcolemmal disruption

Question 104

TABLE 12-5 – Evolution of Morphologic Changes in Myocardial Infarction

IRREVERSIBLE INJURY

Answer 104

Time : 4–12 hr
Gross Features : Dark mottling (occasional)
Light Microscope: Early coagulation necrosis; edema;
hemorrhage
Electron Microscope: Sarcolemmal disruption; mitochodrial amorphous densities

Question 105

TABLE 12-5 – Evolution of Morphologic Changes in Myocardial Infarction

IRREVERSIBLE INJURY

Answer 105

Time :12–24 hr
Gross Features : Dark mottling
Light Microscope: Ongoing coagulation necrosis; pyknosis of nuclei; myocyte hypereosinophilia; marginal contraction band necrosis; early neutrophilic infiltrate
Electron Microscope: Sarcolemmal disruption; mitochodrial amorphous densities

Question 106

TABLE 12-5 – Evolution of Morphologic Changes in Myocardial Infarction

IRREVERSIBLE INJURY

Answer 106

Time : 1–3 days
Gross Features : Mottling with yellowtan infarct center
Light Microscope:Coagulation necrosis, with loss of nuclei and striations; brisk interstitial infiltrate of neutrophils
Electron Microscope: Sarcolemmal disruption; mitochodrial amorphous densities

Question 107

TABLE 12-5 – Evolution of Morphologic Changes in Myocardial Infarction

IRREVERSIBLE INJURY

Answer 107

Time : 3–7days
Gross Features : Hyperemic border;
central yellow-tan softening
Light Microscope:Beginning disintegration of dead myofibers,with dying neutrophils; early phagocytosis of
dead cells by macrophages at infarct border
Electron Microscope: Sarcolemmal disruption; mitochodrial amorphous densities

Question 108

TABLE 12-5 – Evolution of Morphologic Changes in Myocardial Infarction

IRREVERSIBLE INJURY

Answer 108

Time : 7–10 days
Gross Features :Maximally yellow-tan
and soft, with depressed red-tan margins
Light Microscope:Well-developed phagocytosis of dead cells; early formation of fibrovascular granulation tissue at margins
Electron Microscope: Sarcolemmal disruption; mitochodrial amorphous densities

Question 109

TABLE 12-5 – Evolution of Morphologic Changes in Myocardial Infarction

IRREVERSIBLE INJURY

Answer 109

Time : 10 –14 days
Gross Features :Red-gray depressed
infarct bordersand soft, with depressed red-tan margins
Light Microscope:Well-established granulation tissue with new blood vessels and collagen deposition
Electron Microscope: Sarcolemmal disruption; mitochodrial amorphous densities

Question 110

TABLE 12-5 – Evolution of Morphologic Changes in Myocardial Infarction

IRREVERSIBLE INJURY

Answer 110

Time :2–8 wk
Gross Features :Gray-white scar,
progressive from border toward core of infarct
Light Microscope:Increased collagen deposition, with decreased cellularity
Electron Microscope: Sarcolemmal disruption; mitochodrial amorphous densities

Question 111

TABLE 12-5 – Evolution of Morphologic Changes in Myocardial Infarction

IRREVERSIBLE INJURY

Answer 111

Time :>2 mo
Gross Features :Scarring complete
Light Microscope:Dense collagenous scar
Electron Microscope: Sarcolemmal disruption; mitochodrial amorphous densities

Question 112

Answer 112

FIGURE 12-13 Distribution of myocardial ischemic necrosis correlated with the location
and nature of decreased perfusion. Left, The positions of transmural acute infarcts
resulting from occlusions of the major coronary arteries; top to bottom, left anterior
descending, left circumflex, and right coronary arteries. Right, The types of infarcts that
result from a partial or transient occlusion, global hypotension, or intramural small vessel
occlusions

Question 113

Describe the involvement of transmural infarcts.

Answer 113

Nearly all transmural infarcts involve at least a portion of the left ventricle (comprising the free wall and ventricular septum) and encompass nearly the entire perfusion zone of the occluded coronary artery save for a narrow rim (∼0.1 mm) of preserved subendocardial myocardium
that is sustained by the diffusion of oxygen and nutrients from the ventricular lumen.

Question 114

Of MIs caused by a right coronary obstruction, 15% to 30% extend from the posterior free wall
of the septal portion of the left ventricle into the adjacent right ventricular wall. Isolated
infarction of the right ventricle is unusual (1% to 3% of cases), as is infarction of the atria.

Question 115

The frequencies of involvement of each of the three main arterial trunks and the
corresponding sites of myocardial lesions resulting in infarction (in the typical right dominant
heart) are as follows ( Fig. 12-13A ):

Answer 115

• Left anterior descending coronary artery (40% to 50%): infarcts involving the anterior wall of left ventricle near the apex; the anterior portion of ventricular septum; and the apex circumferentially
• • Right coronary artery (30% to 40%): infarcts involving the inferior/posterior wall of left ventricle; posterior portion of ventricular septum; and the inferior/posterior right ventricular free wall in some cases
• • Left circumflex coronary artery (15% to 20%): infarcts involving the lateral wall of left ventricle except at the apex

Question 116

In the frequencies of involvement of each of the three main arterial trunks and the corresponding sites of myocardial lesions resulting in infarction (in the typical right dominant
heart)

Which has the highest percentage?

Answer 116

Left anterior descending coronary artery (40% to 50%)

Question 117

Left anterior descending coronary artery (40% to 50%): what are involved?

Answer 117

infarcts involving the:

• anterior wall of left ventricle near the apex;
• the anterior portion of ventrcular septum; and the
• apex circumferentially

Question 118

Right coronary artery (30% to 40%):

What are the infarcts involved?

Answer 118

• infarcts involving the inferior/posterior wall of left ventricle;
• posterior portion of ventricular septum; and the
• inferior/posterior right ventricular free wall in some cases

Question 119

Left circumflex coronary artery (15% to 20%):

What are involved?

Answer 119

infarcts involving the lateral wall of left
ventricle except at the apex

Question 120

Other locations of critical coronary arterial lesions causing infarcts are sometimes encountered, such as the

Answer 120

• left main coronary artery,
• the secondary branches of the left
• anterior descending coronary artery, or the
• marginal branches of the left circumflex coronary artery.

Question 121

The gross and microscopic appearance of an infarct depends on the duration of
survival of the patient following the MI.

Areas of damage undergo a progressive
sequence of morphologic changes that consist of typical ischemic coagulative necrosis (the predominant mechanism of cell death in MI, although apoptosis may also occur), followed by
inflammation and repair that closely parallels tissue responses to injury at other sites.

Question 122

Early recognition of acute MI can be difficult, particularly when death has occurred within a
few hours after the onset of symptoms.

MIs less than 12 hours old , what can be seen in the gross examination?

Answer 122

are usually not apparent
on gross examination.

Question 123

If the patient died of MI at least 2 to 3 hours after the infarct, however, it is
possible to highlight the area of necrosis by what procedure?

Answer 123

• *immersion of tissue slices in a solution of**
• *triphenyltetrazolium chloride**.

This histochemical stain imparts a brick-red color to intact, noninfarcted myocardium where dehydrogenase (e.g., lactate dehydrogenase) activity is preserved.

Because dehydrogenases leak out through the damaged membranes of dead cell, an infarct appears as an unstained pale zone ( Fig. 12-14 ). By 12 to 24 hours an infarct can be identified grossly in transverse slices as a reddish-blue area of discoloration caused by stagnated, trapped blood.

Thereafter, the infarct becomes progressively more sharply defined, yellow-tan, and soft.

By 10 days to 2 weeks, it is rimmed by a hyperemic zone of highly vascularized granulation tissue.

Over the succeeding weeks, the injured region evolves to a fibrous scar.

Question 124

The histopathologic changes also proceed in a fairly predictable sequence (summarized in
Fig. 12-15 ).

The typical changes of coagulative necrosis become detectable in the first what hours and what apperance?

Answer 124

6 to 12 hours.

“Wavy fibers” may be present at the periphery of the infarct; these changes probably result from the forceful systolic tugs of the viable fibers on immediately adjacent, noncontractile dead fibers, which stretches and folds them

An additional sublethal ischemic change may be seen in the margins of infarcts: so-called vacuolar degeneration or myocytolysis, which takes the form of large vacuolar spaces within cells that probably
contain water.

The necrotic muscle elicits acute inflammation (most prominent between 1 and 3 days).

Thereafter macrophages remove the necrotic myocytes (most pronounced at 3 to 7 days), and the damaged zone is progressively replaced by the ingrowth of highly vascularized granulation tissue (most prominent at 1 to 2 weeks); as healing progresses, this is replaced by fibrous tissue. In most instances, scarring is well advanced by the end of the sixth week, but the efficiency of repair depends on the size of the original lesion

Question 125

What is myocytolysis?

Answer 125

An additional sublethal ischemic change may be seen in the margins of infarcts: so-called vacuolar degeneration or myocytolysis, which takes the form of large vacuolar spaces within cells that probably
contain water.

Question 126

Why do infarct heals form its margins towards its center?

Answer 126

Since healing requires the participation of inflammatory cells that migrate to the region of
damage through intact blood vessels, which oftensurvive only at the infarct margins, the
infarct heals from its margins toward its center.

Thus, a large infarct may not heal as quickly
or as completely as a small one.

A healing infarct may appear nonuniform, with the mostadvanced healing at the periphery.

Once a lesion is completely healed, it is impossible to
determine its age (i.e., the dense fibrous scar of 8-week-old and 10-year-old infarcts may look
identical).

Question 127

What is extension?

Answer 127

Infarcts may expand beyond their original borders over a period of days to weeks via a
process of repetitive necrosis of adjacent regions (extension).

In such cases, there is a central zone in which healing is more advanced than the periphery of the infarct.

This contrasts with the appearance of a simple infarct described above, in which the most
advanced repair is peripheral.

Infarct extension may occur because of retrograde propagation of a thrombus, proximal vasospasm, progressively impaired cardiac contractility that renders flow through moderate stenoses insufficient, the deposition of platelet-fibrin microemboli, or
an arrhythmia that impairs cardiac function.

Question 128

Answer 128

FIGURE 12-14 Acute myocardial infarct, predominantly of the posterolateral left ventricle,
demonstrated histochemically by a lack of staining by triphenyltetrazolium chloride in areas
of necrosis (arrow).

The staining defect is due to the enzyme leakage that follows cell death.

Note the myocardial hemorrhage at one edge of the infarct that was associated with
cardiac rupture, and the anterior scar (arrowhead), indicative of old infarct. Specimen is
oriented with the posterior wall at the top.
Ischemic Heart Disease
1023

Question 129

Answer 129

FIGURE 12-15 Microscopic features of myocardial infarction and its repair.

• A, One-day-old infarct showing coagulative necrosis and wavy fibers (elongated and narrow, as compared with adjacent normal fibers at right). Widened spaces between the dead fibers contain edema fluid and scattered neutrophils.
• B, Dense polymorphonuclear leukocytic infiltrate in area of acute myocardial infarction of 3 to 4 days’ duration.
• C, Nearly complete removal of necrotic myocytes by phagocytosis (approximately 7 to 10 days).
• D, Granulation tissuecharacterized by loose collagen and abundant capillaries.
• E, Well-healed myocardial infarct with replacement of the necrotic fibers by dense collagenous scar. A few residual cardiac muscle cells are present.

Question 130

We now consider interventions that seek to limit infarct size by salvaging myocardium that is not
yet necrotic.

Answer 130

Infarct Modification by Reperfusion.

Question 131

What is the most effective way to “ rescue” ischemic myocardium threatened by infarction?

Answer 131

The most effective way to “rescue” ischemic myocardium threatened by infarction is to restore
myocardial blood flow as rapidly as possible, a process referred to as reperfusion.

Question 132

What is reperfusion?

Answer 132

The most effective way to “rescue” ischemic myocardium threatened by infarction is to restore
myocardial blood flow as rapidly as possible, a process referred to as reperfusion.

Question 133

Although
reperfusion can often be accomplished, reperfusion may also trigger deleterious complications.

T or F

Answer 133

True

Although
reperfusion can often be accomplished, reperfusion may also trigger deleterious complications,
including arrhythmias, myocardial hemorrhage with contraction bands, irreversible cell damage
superimposed on the original ischemic injury (reperfusion injury), microvascular injury, and
prolonged ischemic dysfunction (myocardial stunning)

Question 134

What is reperfusion injury?

Answer 134

, irreversible cell damage
superimposed on the original ischemic injury (reperfusion injury), microvascular injury, and

Question 135

What is myocardial stunning?

Answer 135

prolonged ischemic dysfunction (myocardial stunning)

Question 136

What is often used in an attempt to
dissolve, mechanically alter, or bypass the lesion that initiated the acute MI.

Answer 136

Coronary intervention (i.e., thrombolysis, angioplasty,
stent placement, or coronary artery bypass graft [CABG] surgery) is often used in an attempt to
dissolve, mechanically alter, or bypass the lesion that initiated the acute MI.

The purpose of
these treatments is to restore blood flow to the area at risk for infarction and rescue the
ischemic(but not yet necrotic) heart muscle.Because loss of myocardial viability in infarction is
progressive, occurring over a period of at least several hours early reperfusion can salvage myocardium and thereby limit infarct size, with consequent
improvement in both short- and long-term function and survival.

Question 137

The potential benefit of reperfusion is related to

Answer 137

• (1) the rapidity with which the coronary obstruction is alleviated (the first 3 to 4 hours following onset are critical) and
• (2) the extent of correction of the vascular occlusion and the underlying causal lesion.For example, thrombolysis can remove a thrombus occluding a coronary artery, but does not alter the underlying atherosclerotic plaque that initiated it. In contrast, percutaneous transluminal coronary angioplasty (PTCA) with stent placement not only eliminates a thrombotic occlusion but also can relieve some of the original obstruction and instability caused by the underlying disrupted plaque. CABG provides flow around a blocked vessel.

Question 138

Answer 138

FIGURE 12-17 Effects of reperfusion on myocardial viability and function.

Following
coronary occlusion, contractile function is lost within 2 minutes and viability begins to
diminish after approximately 20 minutes. If perfusion is not restored (A), then nearly all
myocardium in the affected region will die.

B, If flow is restored, then some necrosis is
prevented, myocardium is salvaged, and at least some function will return. The earlier reperfusion occurs, the greater the degree of salvage. However, the process of reperfusion itself may induce some damage (reperfusion injury), and return of function of salvaged
myocardium may be delayed for hours to days (post-ischemic ventricular dysfunction) .

Question 139

The outcome following the restoration of blood flow may vary from region to region.

T or F

Answer 139

TRUE

As indicated in Figure 12-16A , reperfusion of myocardium within 20 minutes of the onset of
ischemia may completely prevent necrosis. Reperfusion after a longer interval may not prevent
all necrosis but can salvage at least some myocytes that would have otherwise died.

Recall that (1) severe ischemia does not cause immediate cell death even in the most severely
affected regions of myocardium, and (2) not all regions of myocardium are equally ischemic.

Question 140

What is the appearance of the reperfused infarct?

Answer 140

A
reperfused infarct is usually hemorrhagic because the vasculature is injured during the period
of ischemia and leaks when flow is restored.

Question 141

What is the microscopic appearance of a reperfused infarct?

Answer 141

Microscopic examination reveals that myocytes that
were irreversibly injured at the time of reperfusion often contain contraction bands, intensely
eosinophilic intracellular “stripes” composed of closely packed sarcomeres.

These result from
the exaggerated contraction of myofibrils when perfusion is reestablished, at which time the
interior of dead cells with damaged plasma membranes are exposed to a high concentration of
calcium ions from the plasma.

Thus, reperfusion not only salvages reversibly injured cells but also alters the morphology of lethally injured cells.

Question 142

Thus, reperfusion not only salvages reversibly injured cells but also alters the morphology of lethally injured cells.

T or F

Answer 142

True

In addition to its benefits, reperfusion may also have some deleterious effects on the vulnerable
ischemic myocardium (reperfusion injury; see Fig. 12-17B ). [52]

The clinical significance of
myocardial reperfusion injury is uncertain.

As discussed in Chapter 1 , reperfusion injury may
be mediated by oxidative stress, calcium overload, and potentially inflammation initiated during
reperfusion.

Reperfusion-induced microvascular injury causes not only hemorrhage but also endothelial swelling that occludes capillaries and may limit the reperfusion of critically injured myocardium (called no-reflow).

Question 143

What is no-reflow?

Answer 143

Reperfusion-induced microvascular injury causes not only hemorrhage but also
endothelial swelling that occludes capillaries and may limit the reperfusion of critically injured
myocardium

Question 144

What is stunned myocardium?

Answer 144

Biochemical abnormalities may also persist for a period of days to several weeks in myocytes that are rescued from ischemia by reperfusion.

These are thought to underlie a phenomenon
referred to as stunned myocardium, a state of reversible cardiac failure that usually recovers
after several days. [53]

Reperfusion also frequently induces arrhythmias.

Question 145

Reperfusion also frequently induces arrhythmias

Tor F

Answer 145

True

Question 146

What is hibernation of the myocardium?

Answer 146

Myocardium that is
subjected to chronic, sublethal ischemia may also enter into a state of lowered metabolism and
function that is referred to as hibernation. [54]

Question 147

How can hibernating myocardium be restored?

Answer 147

The function of hibernating myocardium may be
restored by revascularization (e.g., by CABG surgery, angioplasty, or stenting).

Question 148

What is preconditioning?

Answer 148

Paradoxically,
repetitive short-lived transient severe ischemia may protect the myocardium against infarction
(a phenomenon known as preconditioning) by mechanisms that are not understood

Question 149

How is MI diagnosed?

Answer 149

MI is diagnosed by clinical symptoms, laboratory tests for the presence of myocardial proteins in
the plasma, andcharacteristic electrocardiographic changes.

Question 150

What is the presentation of MI?

Answer 150

Patients with MI often present with
a rapid, weak pulse and profuse sweating (diaphoresis).

Dyspnea due to impaired contractility
of the ischemic myocardium and the resultant pulmonary congestion and edema is common.
However, in about 10% to 15% of patients the onset is entirely asymptomatic and the disease is
discovered only by electrocardiographic changes or laboratory tests that show evidence of
myocardial damage (see below).

Question 151

What age group does “ silent” MIs particularly happen?

Answer 151

Such “silent” MIs are particularly common in elderly patients
and in the setting of diabetes mellitus.

Question 152

The laboratory evaluation of MI is based on what?

Answer 152

The laboratory evaluation of MI is based on measuring the blood levels of proteins that leak out
of fatally injured myocytes; these molecules include myoglobin, cardiac troponins T and I, the
MB fraction of creatine kinase (CK-MB), lactate dehydrogenase, and many others ( Fig. 12-18
). [56]

Question 153

How can the diagnosis of myocardial injury be established?

Answer 153

The diagnosis of myocardial injury is established when blood levels of these cardiac
biomarkers are increased in the clinical setting of acute ischemia.

The rate of appearance of
these markers in the peripheral circulation depends on several factors, including their
intracellular location and molecular weight, the blood flow and lymphatic drainage in the area of
the infarct, and the rate of elimination of the marker from the blood.

Question 154

Answer 154

FIGURE 12-18 Release of myocyte proteins in myocardial infarction. Some of these proteins
(e.g., troponin I, C, or T and creatine phosphokinase, MB fraction [CK-MB]) are used as
diagnostic biomarkers.

Question 155

What are the most sensitive and specific biomakers of myocardial damage?

Answer 155

The most sensitive and specific biomarkers of myocardial damage are :

• cardiac-specific proteins, particularly Troponins I and T (proteins that regulate calcium-mediated contraction of cardiac and skeletal muscle). Troponins I and T are not normally detectable in the circulation.

Following an MI, levels of both begin to rise at 2 to 4 hours and peak at 48 hours.

Formerly the “gold standard,” cardiac creatine kinase remains useful.

Question 156

Troponins I and T are not normally detectable in the circulation.

Following an MI, levels of both begin to rise at __________ hours.

Answer 156

2 to 4 hours

Question 157

Troponins I and T are not normally detectable in the circulation.

Following an MI, levels of both begin to rise at 2 to 4 hours and peaks when?

Answer 157

peak at 48 hours.

Question 158

Formerly the “gold standard,” cardiac creatine kinase remains useful.

What is creatinine kinase?

Answer 158

Creatine kinase, an enzyme that is
present in brain, myocardium, and skeletal muscle, is a dimer composed of two isoforms
designated “M” and “B.”

Question 159

What homodimers of CK are predominantly found in cardiac and skeletal muscle?

Answer 159

MM homodimers are found predominantly in cardiac and skeletal muscle

Question 160

What homodimers of CK are brain, lung, and many other tissues?

Answer 160

BB homodimers in brain, lung, and many other tissues;

Question 161

What homodimers of CK are heterodimers principally
in cardiac muscle, with lesser amounts also being found in skeletal muscle?

Answer 161

MB heterodimers principally
in cardiac muscle, with lesser amounts also being found in skeletal muscle.

As a result, the MB
form of creatine kinase (CK-MB) is sensitive but not specific, since it is also elevated when
skeletal muscle is injured.

CK-MB begins to rise within 2 to 4 hours of the onset of MI, peaks at
about 24 hours, and returns to normal within approximately 72 hours. Although the diagnostic
sensitivities of cardiac troponin and CK-MB measurements are similar in the early stages of MI,
elevated troponin levels persist for approximately 7 to 10 days after acute MI, well after CK-MB
levels have returned to normal. Troponin and CK-MB levels peak earlier in patients whose
hearts are successfully reperfused, because proteins are washed out of the necrotic tissue
more rapidly. Unchanged levels of CK-MB and troponin over a period of 2 days essentially
excludes the diagnosis of MI.

Question 162

When does CK-MB begins to rise?

Answer 162

CK-MB begins to rise within 2 to 4 hours of the onset of MI, peaks at about 24 hours, and returns to normal within approximately 72 hours.

Question 163

When does CK-MB peaks and returns to normal?

Answer 163

CK-MB begins to rise within 2 to 4 hours of the onset of MI, peaks at about 24 hours, and returns to normal within approximately 72 hours.

Although the diagnostic
sensitivities of cardiac troponin and CK-MB measurements are similar in the early stages of MI,
elevated troponin levels persist for approximately 7 to 10 days after acute MI, well after CK-MB
levels have returned to normal.

Question 164

What cardiac markers peak earlier in patients whose hearts are successfully reperfused and why?

Answer 164

Troponin and CK-MB levels peak earlier in patients whose hearts are successfully reperfused, because proteins are washed out of the necrotic tissue
more rapidly.

Question 165

What essentially excludes the diagnosis of MI?

Answer 165

Unchanged levels of CK-MB and troponin over a period of 2 days essentially
excludes the diagnosis of MI.

Question 166

Extraordinary progress has been made in the treatment of patients with acute MI. Concurrent
with the decrease in the overall mortality of IHD since the 1960s, the in-hospital death rate has
declined from around 30% to approximately 7% in patients receiving timely therapy.

Half of the
deaths associated with acute MI occur within 1 hour of onset; most of these individuals never
reach the hospital.

What are the therapies done routinely?

Answer 166

Therapies given routinely in the setting of acute MI include:

• aspirin and heparin (to prevent further thrombosis);
• oxygen (to minimize ischemia);
• nitrates (to induce vasodilation and reverse vasospasm);
• beta-adrenergic inhibitors (beta-blockers, to diminish cardiac oxygen demand and decrease the risk of arrythmias);
• angiotensinogen converting enzyme (ACE) inhibitors (to limit venticular dilation);
• and maneuvers that aim to open up blocked vessels, including the administration of fibrinolytic agents, coronary angioplasty with or without stenting, and emergent CABG surgery.

The choice of therapy depends on the clinical

picture and the expertise of the treating institution. Angioplasty is highly effective in skilled
hands, while fibinolytic therapy can be given with almost equivalent efficacy by simple infusion.

Question 167

In general what are the factors associated with a poor prognosis?

Answer 167

In general, factors associated with a poor prognosis include:

• advanced age,
• female gender,
• diabetes mellitus, and,
• as a result of the cumulative loss of functional myocardium,
• previous MI.

Question 168

Despite these interventions, many patients have one or more complications following acute MI,
including the following (some of which are illustrated in Fig. 12-19 ):

Answer 168

• Contractile dysfunction.
• Arrhythmias.
• Myocardial rupture
• Pericarditis
• Right ventricular infarction
• Infarct extension
• Infarct expansion
• Mural thrombus
• Ventricular aneurysm
• Papillary muscle dysfunction
• Progressive late heart failure (chronic IHD is discussed below).

Question 169

Answer 169

FIGURE 12-19 Complications of myocardial infarction. Cardiac rupture syndromes (A–C).

A,Anterior myocardial rupture in an acute infarct (arrow).

B, Rupture of the ventricular septum
(arrow).

C, Complete rupture of a necrotic papillary muscle.

D, Fibrinous pericarditis,
showing a dark, roughened epicardial surface overlying an acute infarct.

E, Early expansion of anteroapical infarct with wall thinning (arrow) and mural thrombus.

F, Large apical left ventricular aneurysm. The left ventricle is on the right in this apical four-chamber view of the heart.

Question 170

How does Contractile dysfunction result as a complication of MI?

Answer 170

Contractile dysfunction.

Myocardial infarcts produce abnormalities in left ventricular function roughly proportional to their size.

There is usually some degree of left
ventricular failure with hypotension, pulmonary vascular congestion, and interstitial
pulmonary transudates,which mayprogress to frank pulmonary edema and respiratory
impairment.

Severe “pump failure” (cardiogenic shock) occurs in 10% to 15% of patients
following acute MI, generally those with a large infarct (>40% of the left ventricle).
Cardiogenic shock has a nearly 70% mortality rate and accounts for two thirds of inhospital
deaths.

Question 171

How does arrhythmias result as complication in MI?

Answer 171

Arrhythmias.

Many patients have myocardial irritability and/or conduction disturbances
following MI that lead to potentially fatal arrhythmias.

Question 172

MI-associated arrhythmias include

Answer 172

• sinus bradycardia,
• heart block (asystole),
• tachycardia,
• ventricular premature
  contractions or ventricular tachycardia,
• and ventricular fibrillation.

Because of the location of portions of the atrioventricular conduction system (bundle of His) in the inferoseptal myocardium, infarcts of this region may also be associated with heart block.

Question 173

How does myocardial rupture results as complication of MI?

Answer 173

Myocardial rupture.

The cardiac rupture syndromes result from softening and weakening of the necrotic and subsequently inflamed myocardium.

Question 174

The cardiac rupture syndromes result from softening and weakening of the necrotic and subsequently inflamed myocardium.

Answer 174

They include

(1) rupture of the ventricular free wall (most common), with hemopericardium and cardiac
tamponade ( Fig. 12-19A );

(2) rupture of the ventricular septum (less common), leading to an acute VSD and left-to-right shunting ( Fig. 12-19B ); and
(3) papillary muscle rupture (least common), resulting in the acute onset of severe mitral regurgitation ( Fig. 12-19C ).

Question 175

What is the most common myocardial rupture?

Answer 175

(1) rupture of the ventricular free wall (most common), with hemopericardium and cardiac
tamponade ( Fig. 12-19A );

Question 176

2) rupture of the ventricular septum (less common) leading to what?

Answer 176

to an acute VSD and left-to-right shunting

Question 177

What is the least common rupture?

Answer 177

(3) papillary muscle rupture (least common), resulting in the acute onset of severe mitral regurgitation ( Fig. 12-19C ).

Question 178

When does free-wall rupture most frequent?

Answer 178

Free-wall rupture is most frequent 3 to 7 days after MI, when coagulative
necrosis, neutrophilic infiltration, and lysis of the myocardial connective tissue have appreciably weakened the infarcted myocardium (mean, 4 to 5 days; range, 1 to 10 days).

Question 179

What is the most common site for postinfarction free-wall rupture?

Answer 179

The anterolateral wall at the midventricular level is the most common site for postinfarction free-wall rupture.

Question 180

What are the risk factors for free-wall rupture?

Answer 180

Risk factors for free-wall rupture include:

• age over 60,
• female gender,
• and preexisting hypertension.

This complication occurs less frequently in

patients without prior MI because associated fibrotic scarring tends to inhibit myocardial
tearing.

Acute free-wall ruptures are usually rapidly fatal. However, a fortuitously located
pericardial adhesion that partially aborts a rupture may result in a false aneurysm
(localized hematoma communicating with the ventricular cavity).

The wall of a false
aneurysm consists only of epicardium and adherent parietal pericardium and thus many
still ultimately rupture

Question 181

Why does free wall rupture less commonly occurs in patients without prior MI?

Answer 181

This complication occurs less frequently in

patients without prior MI because associated fibrotic scarring tends to inhibit myocardial
tearing.

Question 182

How does Pericarditis result as complication of MI?

Answer 182

Pericarditis.

A fibrinous or fibrinohemorrhagic pericarditis (Dressler syndrome) usually
develops about the second or third day following atransmural infarct as a result of
underlying myocardial inflammation

Question 183

How does righ tventricular infarction result as complication of MI?

Answer 183

Right ventricular infarction.

Isolated infarction of the right ventricle is unusual, but
infarction of some right ventricular myocardium often accompanies ischemic injury of the
adjacent posterior left ventricle and ventricular septum.

Right ventricular infarcts of
either type cause acute right-sided heart failure associated with pooling of blood in the
venous circulation and systemic hypotension

Question 184

How does Infarct extension result as complication of MI?

Answer 184

Infarct extension.

New necrosis may occur adjacent to an existing infarct.

Question 185

How does infarct extension results as complication of Infarct extension?

Answer 185

Infarct extension.

New necrosis may occur adjacent to an existing infarct.

Question 186

How does Infarct expansion result as a complication of MI?

Answer 186

Infarct expansion.

As a result of the weakening of necrotic muscle, there may be disproportionate stretching, thinning, and dilation of the infarct region (especially with anteroseptal infarcts), which is often associated with mural thrombus ( Fig. 12-19E ).

Question 187

How does Mural thrombus result as a complication of MI?

Answer 187

Mural thrombus.

With any infarct, the combination of a local abnormality in contractility (causing stasis) and endocardial damage (creating a thrombogenic surface) can foster mural thrombosis ( Chapter 4 ) and potentially thromboembolism.

Question 188

How does ventricular aneurysm result as complicaiton of MI?

Answer 188

Ventricular aneurysm.

In contrast to the false aneurysms mentioned above, true aneurysms of the ventricular wall are bounded by myocardium that has become scarred.

Aneurysms of the ventricular wall are a late complication of large transmural infarcts that
experience early expansion.

The thin scar tissue wall of an aneurysm paradoxically
bulges during systole ( Fig. 12-19F ).

Question 189

What are the complications of ventricular aneurysms?

Answer 189

Complications of ventricular aneurysms include:

• mural thrombus,
• arrhythmias,
• and heart failure;
• rupture of the tough fibrotic wall is not a concern.

Question 190

How does Papillary muscle dysfunction result as a complication of MI?

Answer 190

Papillary muscle dysfunction .

As mentioned above, rupture of a papillary muscle may
occur following an MI.

More frequently, postinfarct mitral regurgitation results from
ischemic dysfunction of a papillary muscle and underlying myocardium and later from papillary muscle fibrosis and shortening, or from ventricular dilation (see below).

Question 191

The risk of specific postinfarct complications and the prognosis depend primarily on the infarct
size, location, and thickness(subendocardial or transmural).

Answer 191

The risk of specific postinfarct complications and the prognosis depend primarily on the infarct
size, location, and thickness (subendocardial or transmural).

Large transmural infarcts yield a
higher probability of cardiogenic shock, arrhythmias, and late CHF.

Patients with anterior
transmural infarcts are at greatest risk for free-wall rupture, expansion, mural thrombi, and
aneurysm. In contrast, posterior transmural infarcts are more likely to be complicated by
conduction blocks, right ventricular involvement, or both; when acute VSDs occur in this area
they are more difficult to manage.

Overall, however, patients with anterior infarcts have a worse clinical course than those with inferior (posterior) infarcts. With subendocardial infarcts, only
rarely do pericarditis, rupture, and aneurysms occur.

Question 192

What is ventricular remodeling?

Answer 192

In addition to the sequence of repair in the infarcted tissues described above, the noninfarcted segments of the ventricle undergo hypertrophy and dilation; collectively, these changes are
termed ventricular remodeling.

The compensatory hypertrophy of noninfarcted myocardium is initially hemodynamically beneficial.

However, this adaptive effect may be overwhelmed by
ventricular dilation (with or without ventricular aneurysm) and increased oxygen demand, which
can exacerbate ischemia and depress cardiac function.

There may also be changes in
ventricular shape and stiffening of the ventricle due to scar formation and hypertrophy that further diminish cardiac output. Some of these deleterious effects appear to be reduced by ACE inhibitors, which lessen the ventricular dilation that occurs after MI.

Question 193

What are the most important prognosis factor for MI?

Answer 193

Long-term prognosis after MI depends on many factors, the most important of which are the
quality of residual left ventricular functionand theextent of vascular obstructions in vessels that
perfuse the viable myocardium.

The overall total mortality within the first year is about 30%.

Thereafter there is a 3% to 4% mortality among survivors with each passing year.

Infarct
prevention through control of risk factors in individuals who have never experienced MI (primary prevention) and prevention of reinfarction in those who have recovered from an acute MI (secondary prevention) are important strategies that have received much attention and achieved considerable success.

Question 194

Answer 194

FIGURE 12-20 Schematic of the various pathways in the progression of ischemic heart
disease (IHD), showing the interrelationships among coronary artery disease, acute plaque
change, myocardial ischemia, myocardial infarction, chronic IHD, congestive heart failure, and sudden cardiac death.

Question 195

What is Chronic IHD?

Answer 195

The designation chronic IHD is used here to describe progressive heart failure as a
consequence of ischemic myocardial damage.

Question 196

What is ischemic cardiomyopathy?

Answer 196

The term ischemic cardiomyopathy is often used
by clinicians to describe chronic IHD.

In most instances there has been prior MI and sometimes
noninfarcted myocardium(see earlier discussion of cardiac hypertrophy).

However, in other cases severe obstructive
coronary artery disease may present as chronic IHD in the absence of prior infarction

Question 197

In other cases severe obstructive
coronary artery disease may present as chronic IHD in the absence of prior infarction

T or F

Answer 197

However, in other cases severe obstructive
coronary artery disease may present as chronic IHD in the absence of prior infarction

Question 198

What is the morphology of people with chronic IHD?

Answer 198

Morphology.

Hearts from patients with chronic IHD are usually enlarged and heavy, due to left ventricular hypertrophy and dilation.

Invariably there is some degree of obstructive
coronary atherosclerosis.

Discrete scars representing healed infarcts are usually present.

The mural endocardium may have patchy, fibrous thickenings, and mural thrombi may be
present.

Question 199

What are the Microscopic findings of chronic IHD?

Answer 199

Microscopic findings include myocardial hypertrophy, diffuse subendocardial
vacuolization, andfibrosis.

Question 200

What is the clinical presentation of CHF?

Answer 200

Clinically, progressive CHF may occur in patients who have had past episodes of MI or anginal
attacks.

In some individuals, however, progressive myocardial damage is silent, and heart
failure is the first indication of IHD.

The diagnosis rests largely on the exclusion of other cardiac diseases. Patients with chronic IHD account for nearly half of cardiac transplant recipients.

Question 201

What is sudden cardiac death?

Answer 201

Sudden cardiac death (SCD) strikes down about 300,000 to 400,000 individuals annually in the
United States.

It is defined as unexpected death from cardiac causes in individuals without symptomatic heart disease or early after symptom onset (usually within 1 hour).

Question 202

SCD is usually result from what?

Answer 202

SCD is usually
the consequence of a lethal arrhythmia (e.g., asystole, ventricular fibrillation).

It most frequently
occurs in the setting of IHD; in some cases, SCD is the first clinical manifestation of IHD.

Question 203

What is the first clinical manifestation of IHD?

Answer 203

It most frequently
occurs in the setting of IHD; in some cases, SCD is the first clinical manifestation of IHD.

Question 204

What is the most common trigger for fatal arrhyhmias?

Answer 204

Acute myocardial ischemia is the most common trigger for fatal arrhythmias . [57]

Although ischemic injury can affect the conduction system and create electromechanical cardiac instability, fatal arrhythmias usually result from acute ischemia-induced electrical instability of
myocardium that is distant from the conduction system.

Arrythmogenic foci are often located
adjacent to scars left by old MIs.

Question 205

Fatal arrhythmias usually result from what?

Answer 205

Although ischemic injury can affect the conduction system and create electromechanical cardiac instability,

fatal arrhythmias usually result from acute ischemia-induced electrical instability of
myocardiumthat isdistant from the conduction system.

Question 206

Where doest Arrhythmogenic foci often located?

Answer 206

Arrhythmogenic foci are often located
adjacent to scars left by old MIs.

Question 207

Nonatherosclerotic conditions associated with SCD include

Answer 207

• • Congenital structural or coronary arterial abnormalities
• • Aortic valve stenosis
• • Mitral valve prolapse
• • Myocarditis
• • Dilated or hypertrophic cardiomyopathy
• • Pulmonary hypertension
• • Hereditary or acquired cardiac arrhythmias
• • Cardiac hypertrophy of any cause (e.g., hypertension)
• • Other miscellaneous causes, such as systemic metabolic and hemodynamic alterations,
• catecholamines, and drugs of abuse, particularly cocaine and methamphetamine.

Question 208

What is the morphology of SCD?

Answer 208

Morphology.

Marked coronary atherosclerosis with a critical (>75%) stenosis involving one more of the three major vessels is present in 80% to 90% of SCD victims; only 10% to
20% of cases are of nonatherosclerotic origin.

Usually there are high-grade stenoses
(>90%); in approximately one half, acute plaque disruption is observed, and in approximately
25% diagnostic changes of acute MI are seen. [58]

This suggests that many patients who die
suddenly are suffering an MI, but the short interval from onset to death precludes the
development of diagnostic myocardial changes. However, in one study of those who had
been successfully resuscitated from a sudden cardiac arrest, a new MI occurred in only 39%
of the patients. [59]

Thus, most SCD is not associated with acute MI; most of these deaths are thought to result from myocardial ischemia–induced irritability that initiates malignant
ventricular arrhythmias.

Scars of previous infarcts and subendocardial myocyte vacuolization indicative of severe chronic ischemia are common in such patients.

Question 209

What is the importance of heritable conditions associated with SCD?

Answer 209

Heritable conditions associated with SCD are of importance, since they may provide a basis for
intervention in surviving family members. [60]

Some of these disorders are associated with
recognizable anatomic abnormalities (e.g., congenital anomalies, hypertrophic cardiomyopathy,
mitral valve prolapse).

However, other heritable arrhythmias can precipitate sudden death in the absence of structural cardiac pathology (so-called primary electrical disorders).

These
syndromes can only be diagnosed definitively by genetic testing, which is performed in those
with a positive family history or an unexplained nonlethal arrhythmia.

Question 210

What are the primary electrical abnormalities of the heart that predispose to SCD include what?

Answer 210

The primary electrical abnormalities of the heart that predispose to SCD include:

• long QT syndrome,
• Brugada syndrome,
• short QT syndrome,
• catecholaminergic polymorphic ventricular tachycardia,
• Wolff-Parkinson-White syndrome,
• congenital sick sinus syndrome,
• and isolated cardiac conduction disease. [61]

Question 211

What is the most important Nonatherosclerotic conditions associated with SCD?

Answer 211

The most important of these disorders are the so-called channelopathies, which are caused by mutations in genes that are required for normal ion
channel function. [62]

These disorders (mostly with autosomal-dominant inheritance) either involve genes that encode the ion channels (including Na + , K + , and Ca + ), or accessory proteins that are essential for the normal function of the same channels, which are responsible
for conducting the electrical currents that mediate contraction of the heart.

Question 212

What is the prototype of channelopathies associated with SCD?

Answer 212

T he prototype is the long QT syndrome, characterized by prolongation of the QT segment in electrocardiograms and susceptibility to malignant ventricular arrhythmias. Mutations in seven different genes
account for the majority of cases of long QT syndrome.

The most frequent mutations are in the
gene encoding KCNQ1 and result in decreased potassium currents.

Ion channels are needed
for the normal function of many tissues, and certain channelopathies are also associated with
skeletal muscle disorders and diabetes; however, the most common cardiac channelopathies
are isolated disorders of the heart

Question 213

How is the prognosis of many patients vulnerable to SCD improved?

Answer 213

The prognosis of many patients vulnerable to SCD, including those with chronic IHD, is
markedly improved by implantation of a pacemaker or an automatic cardioverter defibrillator,
which senses and electrically counteracts an episode of ventricular fibrillation.