Irreversible Injury

½–4 hr None Usually none; variable waviness of fibers at border Sarcolemmal disruption; mitochondrial amorphous

densities

4–12 hr Occasionally dark mottling Beginning coagulation necrosis; edema; hemorrhage

12–24 hr Dark mottling Ongoing coagulation necrosis; pyknosis of nuclei; myocyte

hypereosinophilia; marginal contraction band necrosis;

beginning neutrophilic infiltrate

1–3 days Mottling with yellow-tan infarct center Coagulation necrosis, with loss of nuclei and striations;

interstitial infiltrate of neutrophils

3–7 days Hyperemic border; central yellow-tan

softening

Beginning disintegration of dead myofibers, with dying

neutrophils; early phagocytosis of dead cells by

macrophages at infarct border

7–10 days Maximally yellow-tan and soft, with

depressed red-tan margins

Well-developed phagocytosis of dead cells; early

formation of fibrovascular granulation tissue at margins

10–14 days Red-gray depressed infarct borders Well-established granulation tissue with new blood vessels

and collagen deposition

2–8 wk Gray-white scar, progressive from border

toward core of infarct

Increased collagen deposition, with decreased cellularity

>2 mo Scarring complete Dense collagenous scar

solution of triphenyltetrazolium chloride (TTC). This histochemical stain imparts a brick-red color to intact, noninfarcted myocardium where the dehydrogenase enzymes are preserved.

Because dehydrogenases are depleted in the area of ischemic necrosis (they leak out through the damaged cell membranes), an infarcted area is revealed as an unstained pale zone (while

old scarred infarcts appear white and glistening) ( Fig. 12-15 ). Subsequently, by 12 to 24 hours, an infarct can be identified in routinely fixed gross slices owing to a red-blue hue caused

by stagnated, trapped blood. Progressively thereafter, the infarct becomes a more sharply defined, yellow-tan, somewhat softened area that by 10 days to 2 weeks is rimmed by a hyperemic

zone of highly vascularized granulation tissue. Over the succeeding weeks, the injured region evolves to a fibrous scar.

The histopathologic changes also have a fairly predictable sequence (summarized in Table 12-5 and Figure 12-16 ). Using light microscopic examination of routinely stained tissue

sections, the typical changes of coagulative necrosis become detectable variably in the first 4 to 12 hours. "Wavy fibers" may be present at the periphery of the infarct; these changes

probably result from the forceful systolic tugs by the viable fibers immediately adjacent to the noncontractile dead fibers, thereby stretching and buckling them. An additional but sublethal

ischemic change may be seen in the margins of infarcts: so-called vacuolar degeneration or myocytolysis, involving large vacuolar spaces within cells, probably containing water. This

potentially reversible alteration is particularly frequent in the thin zone of viable subendocardial cells. Subendocardial

Figure 12-15Acute myocardial infarct, predominantly of the posterolateral left ventricle, demonstrated histochemically by a lack of staining by the triphenyltetrazolium chloride (TTC)

stain 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 the oriented with the posterior wall at the top.)

Figure 12-16Microscopic features of myocardial infarction and its repair. A, One-day-old infarct showing coagulative necrosis along with wavy fibers (elongated and narrow), 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 tissue characterized 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.

Figure 12-17Temporal sequence of early biochemical, ultrastructural, histochemical, and histologic findings after onset of severe myocardial ischemia. 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, with progressively smaller benefit occurring as reperfusion is delayed. (Modified with permission from Antman E: Acute myocardial

infarction. In Braunwald E, Zipes DP, Libby P (eds): Heart Disease: A Textbook of Cardiovascular Medicine, 6th ed. Philadelphia, WB Saunders, 2001, pp. 1114–1231.)

Figure 12-18Consequences 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 <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 demonstrate stunning.) Reperfusion beyond 6 hours does not appreciably reduce myocardial

infarct size. Late reperfusion may still have a beneficial effect on reducing or preventing myocardial infarct expansion and left ventricular remodeling. B, Gross and C, microscopic

appearance of myocardium modified by reperfusion. B, Large, densely hemorrhagic, anterior wall acute myocardial infarction from patient with left anterior descending artery thrombus

treated with streptokinase intracoronary thrombolysis (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.

Figure 12-19Complications of myocardial infarction. Cardiac rupture syndromes (A, B, and 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. (A–E, Reproduced by permission from Schoen FJ: Interventional and Surgical Cardiovascular Pathology: Clinical Correlations and Basic Principles, Philadelphia, WB Saunders,

1989.) (F, Courtesy of William D. Edwards, M.D., Mayo Clinic, Rochester, MN.)

Figure 12-20Hypertensive heart disease with marked concentric thickening of the left ventricular wall causing reduction in lumen size. The left ventricle is on the right in this apical fourchamber

view of the heart. A pacemaker is incidentally present in the right ventricle (arrow).

TABLE 12-6-- Disorders Predisposing to Cor Pulmonale

Date: 2016-04-22; view: 937