Myocardial Response.

The consequence of coronary arterial obstruction is the loss of critical blood supply to the myocardium ( Fig. 12-13 ), which induces profound functional, biochemical, and morphologic

consequences. Occlusion of a major coronary artery results in ischemia and, potentially, cell death throughout

Figure 12-13Postmortem 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 artery by an acute thrombus (arrow) and a large zone of myocardial hypoperfusion involving the posterior left and right ventricles, as indicated by arrowheads, and

having almost absent filling of capillaries, that is, less white. The heart has been fixed by coronary arterial perfusion with glutaraldehyde and cleared with methyl salicylate, followed by

intracoronary injection of silicone polymer. Photograph courtesy of Lewis L. Lainey. (Reproduced by permission from Schoen FJ: Interventional and Surgical Cardiovascular Pathology:

Clinical Correlations and Basic Principles. Philadelphia, WB Saunders, 1989, p. 60.)

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

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

ATP, adenosine triphosphate.

leading cause of mortality in IHD patients, can be caused by massive cell injury with mechanical failure but is most often due to ventricular fibrillation caused by myocardial irritability

induced by ischemia or infarction. Interestingly, studies of resuscitated survivors of "sudden death" show that the majority do not develop acute MI; in such cases, myocardial irritability

induced by ischemia presumably led directly to the serious arrhythmia.

The progression of ischemic necrosis in the myocardium is summarized in Figure 12-14 . Irreversible injury of ischemic myocytes occurs first in the subendocardial zone. With more

extended ischemia, a wavefront of cell death moves through the myocardium to involve progressively more of the transmural thickness of the ischemic zone. The precise location, size, and

specific morphologic features of an acute myocardial infarct depend on:

• The location, severity, and rate of development of coronary atherosclerotic obstructions

• 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 alterations in blood pressure, heart rate, and cardiac rhythm.

The necrosis is largely complete within 6 hours in experimental models and humans, involving nearly all of the ischemic myocardial bed at risk supplied by the occluded coronary artery.

Progression of necrosis, however, may follow a more protracted course in some patients (possibly over 6 to 12 hours or longer) in whom the coronary arterial collateral system, stimulated

by chronic ischemia, is better developed and thereby more effective.

Morphology.

The evolution of the morphologic changes in acute MI and its healing are summarized in Table 12-5 .

Nearly all transmural infarcts involve at least a portion of the left ventricle (including the ventricular septum). About 15% to 30% of those that affect the posterior free wall and posterior

portion of the septum transmurally extend into the adjacent right ventricular wall. Isolated infarction of the right ventricle, however, occurs in only 1% to 3% of cases. Associated infarction

of atrial tissue accompanies a large posterior left ventricular infarct in some cases. Transmural infarcts usually encompass nearly the entire perfusion zone of the occluded coronary artery.

Almost always there is a narrow rim (approximately 0.1 mm) of preserved subendocardial myocardium sustained by diffusion of oxygen and nutrients from the lumen.

The frequencies of critical narrowing (and thrombosis) 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:

• Left anterior descending coronary artery (40% to 50%): infarct involves anterior wall of left ventricle

near apex; anterior portion of ventricular septum; apex circumferentially

• Right coronary artery (30% to 40%): infarct involves inferior/posterior wall of left ventricle; posterior portion of ventricular septum; inferior/posterior right ventricular free wall

in some cases

• Left circumflex coronary artery (15% to 20%): infarct involves lateral wall of left ventricle except at apex

Figure 12-14Schematic representation of the 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. This entire region of myocardium (shaded) depends on the occluded vessel for perfusion and is the area at risk. 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. The end result of the obstruction to

blood flow is necrosis of the muscle that was dependent on perfusion from the coronary artery obstructed. Nearly the entire area at risk loses viability. The process is called myocardial

infarction, and the region of necrotic muscle is a myocardial infarct.

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

Date: 2016-04-22; view: 695