Myocardial Infarction

Slide 1 · Myocardial Infarction

Mechanisms · Morphologic evolution · Clinical consequences

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Trace atherothrombosis to ischemic myocyte necrosis.

Distinguish transmural, subendocardial, and microinfarct patterns.

Interpret the chronology of myocardial injury and repair.

Relate troponin, reperfusion, and complications to pathology.

Slide 3 · Myocardial infarction: Definition

Death of cardiac muscle due to prolonged ischemia.

Most commonly arises in the setting of coronary atherosclerosis.

The extent of injury reflects the severity and duration of impaired perfusion.

Myocardial ischemia is not synonymous with irreversible myocardial infarction.

Slide 4 · Atherosclerotic context and susceptibility

Myocardial infarction becomes more frequent with increasing age.

Risk increases with the burden of atherosclerotic risk factors.

Male sex carries higher relative risk through middle age.

Coronary disease becomes increasingly important after menopause.

Slide 5 · Postmenopausal risk: A source-specific caution

The postmenopausal transition is associated with worsened coronary risk.

Hormone replacement therapy has not demonstrated protection against MI.

The source notes possible harm in some contexts, including prothrombotic effects.

Risk modification is not equivalent to hormonal replacement as coronary prevention.

Slide 6 · Typical pathogenesis: Coronary atherothrombosis

Plaque erosion or disruption

Platelet adhesion and activation

Coagulation activation

Occlusive thrombus

A rapidly evolving thrombus may completely obstruct the coronary lumen within minutes.

Slide 7 · Plaque injury exposes thrombogenic material

Endothelial injury, intraplaque hemorrhage, or mechanical forces destabilize the lesion.

Subendothelial collagen and necrotic plaque contents contact circulating blood.

The exposed material initiates platelet and coagulation responses.

Slide 8 · Platelet amplification and vasospasm

Platelet adhesion

Activation and aggregation

TXA₂ · ADP · serotonin

Further aggregation and spasm

Platelet mediators reinforce both thrombus growth and vasoconstriction.

Slide 9 · Coagulation consolidates coronary occlusion

Tissue factor and additional mechanisms activate the coagulation cascade.

Fibrin-rich coagulation is superimposed on platelet aggregates.

A coronary lumen can become fully occluded within minutes.

A plaque need not have produced a critical fixed stenosis before acute rupture.

Slide 10 · Thrombus detection changes with time

Angiography after MI

Observed coronary thrombosis

Interpretation

Within 4 hours

Almost 90% of cases

High detection early after onset

12–24 hours

About 60% of patients

Spontaneous lysis or spasm resolution may occur

Slide 11 · Why early reperfusion can salvage myocardium

Some early coronary occlusions are thrombotic and potentially reversible.

Spontaneous clearing may occur, but prolonged ischemia progressively kills myocytes.

Thrombolysis or angioplasty can limit infarct size when performed early.

Reopening a vessel has maximal benefit while downstream muscle remains viable.

Slide 12 · Infarction without typical atherothrombosis

The source attributes approximately 10% of MIs to other mechanisms.

Reduced flow may reflect coronary vasospasm or embolism.

Small-vessel disease, dissection, systemic hypotension, and major hypertrophy are other causes.

Slide 13 · Coronary vasospasm as a mechanism

Transient severe constriction may occur with or without atherosclerosis.

Cocaine or ephedrine exposure is cited as a potential trigger.

Catecholamines also increase heart rate and contractility, increasing oxygen requirements.

Spasm can impair supply while adrenergic stimulation increases demand.

Slide 14 · Coronary emboli: Potential origins

Left atrial mural thrombi associated with atrial fibrillation.

Infective endocarditis vegetations or intracardiac prosthetic material.

Right-sided or venous emboli crossing a patent foramen ovale.

Slide 15 · Other routes to ischemic necrosis

Small intramural vascular disease, such as vasculitis or amyloid deposition.

Sickle cell disease and coronary vascular dissection.

Severe ventricular hypertrophy or profound systemic hypotension.

Inadequate myocardial protection during cardiac surgery.

Slide 16 · Area at risk: From arterial flow loss to necrosis

Coronary obstruction

Perfusion deficit in a territory

Ischemic dysfunction

Myocyte death if prolonged

The perfusion territory downstream of the culprit artery is the “area at risk.”

Slide 17 · Ischemia rapidly disrupts energetics

Aerobic metabolism ceases within seconds of severe ischemia.

Creatine phosphate and ATP production become inadequate.

Lactate and potentially injurious metabolites accumulate.

Mechanical contractility fails before necrosis becomes established.

Slide 18 · Contractile failure precedes cell death

Severely ischemic myocardium may cease contracting within about one minute.

Early systolic dysfunction can arise while myocytes remain viable.

This disconnect is central to the opportunity for myocardial salvage.

Loss of function is an early physiologic event, not proof of irreversible injury.

Slide 19 · Reversible early ultrastructural injury

Myofibrillar relaxation accompanies loss of mechanical function.

Glycogen stores are depleted during ischemia.

Cellular and mitochondrial swelling develop within minutes.

These earliest changes may still reverse after blood flow is restored.

Slide 20 · Approximate onset of ischemic events

Event

Approximate time after severe ischemia

ATP depletion begins

Seconds

Contractile function lost

Less than 2 minutes

ATP falls to 50%

10 minutes

ATP falls to 10%

40 minutes

Irreversible cell injury

20–40 minutes

Microvascular injury

More than 1 hour

Slide 21 · Duration determines irreversibility

Severe flow reduction to 10% or less of normal can cause necrosis after 20–30 minutes or longer.

Loss of viability progresses across the jeopardized muscle after that threshold.

Infarct extent is usually complete by 6–12 hours without effective salvage.

Slide 22 · Cell membrane failure creates blood biomarkers

Myocyte necrosis

Sarcolemmal disruption

Protein leakage

Circulating biomarkers

Biomarker release requires loss of membrane integrity in injured myocytes.

Slide 23 · Microvascular injury develops later

Myocytes are affected before substantial microvascular injury.

Prolonged ischemia and reperfusion can injure the microcirculation.

Microvascular damage can prevent effective tissue-level reperfusion even if the main artery reopens.

Slide 24 · Why the subendocardium dies first

Subendocardial tissue lies farthest along the flow path from epicardial coronary arteries.

Higher intramural pressures impede perfusion of the inner myocardium.

Ischemic cell death therefore starts near the endocardial surface.

Subendocardial vulnerability reflects both perfusion geometry and tissue pressure.

Slide 25 · Wavefront necrosis can become transmural

Subendocardium

Epicardium

Schematic: Left-to-right indicates wall depth; Vertically separated areas represent distinct myocardial regions.

The conceptual wall is shown after prolonged complete ischemia; Near-complete thickness involvement.

Slide 26 · Infarct extent has multiple determinants

Severity, location, and speed of developing coronary obstruction.

Duration of occlusion and size of the supplied vascular bed.

Metabolic demand, oxygenation, heart rate, and rhythm.

Coronary collaterals and coexisting vasospasm.

Slide 27 · Collateral vessels may limit tissue loss

Intercoronary anastomoses are present in many hearts.

Slow progressive stenosis creates pressure gradients that increase collateral flow.

Collateral enlargement can preserve tissue otherwise deprived of adequate perfusion.

Coronary collateralization modifies the same arterial occlusion’s tissue impact.

Slide 28 · Major coronary perfusion territories

Artery

Typical myocardium supplied

LAD

Apex, anterior LV wall, anterior two-thirds of septum

RCA (right dominant heart)

RV free wall, posterobasal LV wall, posterior third of septum

LCX

Lateral LV wall, usually sparing apex

Slide 29 · Coronary dominance describes septal supply

Dominance is assigned by which artery supplies the posterior third of the septum.

Right coronary dominance is present in approximately 80% of individuals in this source.

RCA occlusion in a right-dominant heart may also damage the left ventricle.

“Dominant” does not mean the artery supplies most LV myocardium.

Slide 30 · LAD infarctions: Principal territory

The LAD is implicated in approximately 40%–50% of infarcts in the source.

Affected areas: Anterior LV near the apex and anterior ventricular septum.

The cardiac apex may be involved circumferentially.

Slide 31 · RCA infarctions: Principal territory

The RCA is implicated in approximately 30%–40% of infarcts in the source.

Affected areas: Inferior/posterior LV wall and posterior septum.

The adjacent right ventricular free wall can also be affected.

Slide 32 · LCX infarctions: Principal territory

The LCX is implicated in approximately 15%–20% of infarcts in the source.

Its characteristic territory is the lateral left ventricular wall.

The apex is ordinarily spared in this typical distribution.

Slide 33 · Three principal patterns of myocardial necrosis

Transmural

Near full-thickness wall necrosis

Typical sustained epicardial occlusion

Coronary territorial pattern

Subendocardial

Inner wall involvement

Transient or partial flow loss

Can follow global hypotension

Microinfarction

Focal injury in small areas

Intramural vascular pathology

Microemboli, spasm, vasculitis

Slide 34 · Transmural necrosis: Full wall-depth pattern

Subendocardium

Epicardium

Schematic: Left-to-right indicates wall depth; Vertically separated areas represent distinct myocardial regions.

A sustained epicardial coronary occlusion may injure nearly the full ventricular wall.

Slide 35 · Regional subendocardial necrosis

Subendocardium

Epicardium

Schematic: Left-to-right indicates wall depth; Vertically separated areas represent distinct myocardial regions.

Early thrombus lysis or restoration of flow can spare outer myocardium.

Slide 36 · Circumferential subendocardial necrosis

Subendocardium

Epicardium

Schematic: Left-to-right indicates wall depth; Vertically separated areas represent distinct myocardial regions.

Systemic hypotension with underlying stenoses can affect the inner myocardium widely.

Slide 37 · Multifocal microinfarction

Subendocardium

Epicardium

Schematic: Left-to-right indicates wall depth; Vertically separated areas represent distinct myocardial regions.

Scattered microinfarcts reflect small intramural vessel injury or obstruction.

Slide 38 · Pathologic aging requires elapsed time

Gross and histologic appearances evolve after the acute event.

Very early infarcts can escape gross recognition.

The appearance reflects ischemic necrosis, inflammation, clearance, and scar formation.

A normal-looking early gross specimen does not exclude acute myocardial infarction.

Slide 39 · Triphenyl tetrazolium chloride highlights necrosis

Viable myocyte LDH activity

TTC produces brick-red tissue

Necrosis loses dehydrogenase activity

Infarct remains pale

This is the source-described histochemical principle—not a reproduced pathology specimen.

Slide 40 · Early gross change is subtle

Infarcts younger than 12 hours are often not visible grossly.

A 2–3-hour-old area of necrosis may be detected using TTC staining.

At 12–24 hours, reddish-blue mottling may become apparent.

Slide 41 · Gross appearance evolves during repair

At 3–7 days: Hyperemic margin around a softening yellow-tan center.

At 7–10 days: Maximal softness and a depressed red-tan border.

During subsequent weeks: Progressive gray-white scar formation.

Slide 42 · Coagulative necrosis is the dominant injury

Irreversible ischemic injury predominantly causes coagulative necrosis.

Loss of nuclei and striations accompanies progressive myocyte death.

Some apoptosis may also occur.

The morphologic sequence reflects necrosis followed by inflammation and replacement repair.

Slide 43 · Early wavy fibers: A mechanical explanation

Necrotic fibers lose active contraction and resist normal force generation.

Adjacent viable myocardium continues to contract.

Dead fibers may be stretched and buckled, producing a wavy appearance.

Slide 44 · First day: Early microscopic evolution

Within 0.5–4 hours, light microscopy is often unrevealing.

By 4–12 hours, edema, hemorrhage, and early coagulative necrosis may be seen.

At 12–24 hours, hypereosinophilia, nuclear pyknosis, and early neutrophils appear.

Slide 45 · Days 1–3: Neutrophilic inflammation

Coagulative necrosis becomes prominent, with loss of myocyte nuclei and striations.

A brisk interstitial neutrophilic infiltrate accompanies acute tissue injury.

This is an inflammatory response to necrotic myocardium.

Slide 46 · Days 3–7: Macrophage clearance

Dead fibers begin to disintegrate and neutrophils die.

Macrophages phagocytose necrotic cells, especially from the infarct margins.

Developing granulation tissue produces a hyperemic peripheral zone.

Slide 47 · Days 7–14: Granulation tissue

Macrophage phagocytosis becomes well established.

New blood vessels and loose collagen appear at the infarct margins.

Collagen accumulation prepares the site for fibrous replacement.

Slide 48 · Weeks to months: Scar maturation

Between 2 and 8 weeks, collagen increases while cellularity falls.

After approximately two months, a dense collagenous scar is complete in the source table.

Once healed, histology cannot reliably date a scar as weeks versus years old.

Slide 49 · Morphology timeline: Acute injury to scar

Interval

Predominant microscopic finding

Typical gross appearance

0.5–4 h

Usually none; possible wavy border fibers

None

4–24 h

Early coagulative necrosis; edema; early neutrophils

Mottling may appear

1–3 d

Necrosis and brisk neutrophils

Yellow-tan center begins

3–7 d

Macrophages; early granulation tissue

Soft center, hyperemic rim

7–14 d

Phagocytosis and vascular granulation tissue

Depressed margins

2–8 wk and later

Progressive collagen to dense scar

Gray-white scar

Slide 50 · Why healing proceeds from the border

Inflammatory cells and ingrowing vessels enter from surviving tissue margins.

Granulation tissue moves inward toward the necrotic core.

Large infarcts may require longer repair than smaller lesions.

Malnutrition, poor vascularity, and anti-inflammatory steroids can impair healing.

Slide 51 · Infarct repair does not regenerate cardiac muscle

Adult cardiomyocytes are terminally differentiated in the source’s account.

The injured zone is replaced by granulation tissue and collagenous scar.

Residual myocardium may hypertrophy, but the necrotic area does not regain myocyte mass.

Slide 52 · Reperfusion: Tissue salvage and its limits

Occluded artery

Prompt restoration of flow

Viable muscle salvaged

Infarct size may be reduced

Earlier perfusion restoration generally preserves more myocardium at risk.

Slide 53 · Pathways to restoring coronary flow

Thrombolysis dissolves an obstructing clot.

Angioplasty restores coronary arterial lumen patency.

Coronary artery bypass grafting can provide an alternative path for perfusion.

These are methods named by the Robbins source, not a treatment-selection guideline.

Slide 54 · Persistent occlusion versus reperfusion

Persistent occlusion

Loss of contraction precedes necrosis

Progressive loss of at-risk viability

Extensive tissue death if prolonged

Early reperfusion

Some ischemic myocardium survives

Reperfusion injury can coexist

Functional recovery may be delayed

Slide 55 · Reperfusion injury: Mechanisms

Mitochondrial injury and membrane permeability alterations.

Calcium-related hypercontracture of myocytes.

Reactive oxygen and nitrogen species injury.

Leukocyte, platelet, and complement-mediated microvascular injury.

Slide 56 · Mitochondrial injury after flow restoration

Ischemia can alter mitochondrial membrane permeability.

Mitochondrial swelling and outer-membrane rupture may release pro-apoptotic contents.

This can add cell injury in tissue exposed to reperfusion.

Slide 57 · Calcium drives contraction-band damage

Ischemia impairs calcium cycling and damages sarcolemmal integrity.

Restored perfusion can intensify uncontrolled actin–myosin contraction.

Hypercontracted sarcomeres become visible as eosinophilic contraction bands.

Contraction-band necrosis is a pathologic consequence of severe calcium dysregulation.

Slide 58 · Reactive species exacerbate injury

Superoxide, hydrogen peroxide, and hydroxyl radicals are cited among reactive species.

Peroxynitrite and hypochlorous acid are also noted by the source.

Oxidative reactions damage membrane proteins and phospholipids.

Slide 59 · No-reflow: Vessel open, tissue still ischemic

Epicardial artery reopened

Microvascular injury persists

Leukocytes and complement contribute

Tissue perfusion may fail

“No reflow” refers to failure of microvascular tissue reperfusion despite removal of the main obstruction.

Slide 60 · Reperfused infarcts may be hemorrhagic

Microvascular damage increases vascular leakiness.

Reperfused infarcted tissue often contains hemorrhage.

Irreversibly injured cells may exhibit contraction-band necrosis.

Reperfusion changes the appearance of injury; It does not reverse already necrotic myocardium.

Slide 61 · Myocardial stunning versus hibernation

Stunned myocardium

After brief ischemia and reperfusion

Contractile dysfunction persists temporarily

Usually recovers over days

Hibernating myocardium

Due to chronic sublethal ischemia

Metabolism and function downregulated

May recover after revascularization

Slide 62 · Classical clinical presentation

Prolonged chest pain, often described as crushing, stabbing, or squeezing.

A rapid, weak pulse and diaphoresis may accompany the episode.

Nausea and vomiting can be associated with posterior-inferior infarction.

Dyspnea may reflect pulmonary congestion due to impaired contractility.

Slide 63 · An infarction may be clinically silent

The source reports up to one quarter of patients as initially asymptomatic.

Diabetic neuropathy is given as one possible setting.

The infarction may only be recognized through ECG findings or biochemical evidence.

Absence of typical pain does not exclude myocardial injury.

Slide 64 · ECG patterns do not simply equal wall anatomy

The source links typical transmural injury with ST-elevation MI terminology.

Subendocardial infarction is often described with non–ST-elevation terminology.

Smaller or differently located infarcts can show nonspecific or absent ECG changes.

These are textbook associations—not a rule that ECG alone proves transmural histology.

Slide 65 · Cardiac troponin becomes a circulating signal

Irreversible myocyte damage

Loss of sarcolemmal integrity

CTnI or cTnT release

Blood concentration increases

Troponins detect myocardial injury; The cause requires clinical interpretation.

Slide 66 · Troponin timing after MI

Cardiac troponin I or T begins rising about 2–4 hours after infarction.

Levels typically peak at 24–48 hours and stay elevated for 7–10 days.

Reperfusion can produce an earlier, higher peak by accelerating washout.

Source-reported kinetics depend on tissue injury, perfusion, drainage, and clearance.

Slide 67 · Troponin elevation is not etiologically specific

Myocarditis or myocardial trauma can also cause marked acute troponin elevation.

Low-level elevation is reported with heart failure, pulmonary embolism, renal failure, and sepsis.

Serial measurements and the entire presentation help distinguish etiologies.

Troponin above a threshold establishes myocardial injury—not its mechanism by itself.

Slide 68 · The pathology-based diagnostic framework

Presenting symptoms and signs

ECG findings

Serial cardiac troponins

Integrated interpretation

The source describes diagnosis as a synthesis of clinical, electrical, and laboratory evidence.

Slide 69 · Therapeutic logic: Interrupt thrombosis

Antiplatelet agents reduce platelet-mediated coronary thrombus propagation.

Anticoagulants target coagulation-dependent thrombus extension.

Prompt reperfusion attempts to salvage viable myocardium.

Mechanistic treatment overview only; No drug doses or contemporary regimen claims.

Slide 70 · Therapeutic logic: Rebalance oxygen supply

Supplemental oxygen is listed for hypoxia or respiratory distress.

Nitrates induce vasodilation and reverse vasospasm.

Beta blockers can lower demand and arrhythmic risk when appropriate.

Treating pain, abnormal hemodynamics, anemia, and respiratory disease can improve the balance.

Slide 71 · Complications reflect tissue loss and instability

Infarct volume and location influence mechanical and electrical consequences.

Large transmural infarcts have increased risk of pump failure, arrhythmias, and rupture.

Residual viable myocardium and ensuing repair determine long-term function.

Slide 72 · Contractile dysfunction and cardiogenic shock

Left ventricular dysfunction generally scales with the extent of infarcted muscle.

Hypotension and pulmonary congestion or edema may occur.

The source associates severe pump failure with infarcts involving about 40% or more of LV muscle.

Slide 73 · Papillary muscle dysfunction and regurgitation

Ischemic papillary muscles can contract poorly without rupturing.

This dysfunction may cause postinfarct mitral regurgitation.

Complete papillary muscle rupture can produce severe acute mitral regurgitation.

Later fibrosis, shortening, or ventricular dilation may also impair valve competence.

Slide 74 · Right ventricular involvement

Isolated right ventricular infarction is uncommon.

RCA-related posteroseptal infarcts may extend into the right ventricle.

Resulting right-sided failure can cause systemic venous pooling and hypotension.

Slide 75 · Three mechanical rupture pathways

LV free-wall rupture

Hemopericardium

Cardiac tamponade

Often rapidly fatal

Septal rupture

Acute ventricular septal defect

Left-to-right shunt

Acute hemodynamic burden

Papillary rupture

Acute structural valve failure

Severe mitral regurgitation

Rapid clinical deterioration

Slide 76 · Why rupture risk peaks during days 3–7

Inflammatory digestion weakens necrotic myocardial architecture.

Early granulation tissue is soft and mechanically fragile.

Wall rupture is most common during the interval of peak necrotic tissue removal.

Tissue repair has a vulnerable interval before collagen stabilizes the infarct.

Slide 77 · Arrhythmias occur early and may be lethal

Ischemic myocardium develops irritability and conduction disturbances.

Manifestations range from bradyarrhythmias and heart block to ventricular fibrillation.

Risk of serious arrhythmia is greatest during the first hour after MI.

Slide 78 · Postinfarct pericarditis

Transmural necrosis may trigger fibrinohemorrhagic pericardial inflammation.

Chest pain and a friction rub may emerge around days 2–3.

A later immune-associated pericarditis is described as Dressler syndrome.

Slide 79 · Wall dilation can promote mural thrombosis

Necrotic wall weakens

Segment thins and dilates

Poor contraction causes stasis

Mural thrombus and embolic risk

Stasis combines with endocardial damage to create a thrombogenic surface.

Slide 80 · Ventricular aneurysm is a late scar complication

A large healed transmural infarct may leave a thin fibrous ventricular wall.

Ventricular aneurysm predisposes to mural thrombi, arrhythmias, and failure.

The scarred aneurysm described here does not rupture.

Distinguish early rupture of friable myocardium from a late fibrous aneurysm.

Slide 81 · Complication patterns depend on infarct topography

Infarct pattern

Complications emphasized by Robbins

Large transmural

Cardiogenic shock, arrhythmia, later heart failure

Anterior transmural

Free-wall rupture, dilation, mural thrombus, aneurysm

Posterior transmural

Conduction block, RV involvement

Subendocardial

Rupture, pericarditis, and aneurysm are uncommon

Slide 82 · Ventricular remodeling: Adaptive, then harmful

Noninfarcted myocardial segments hypertrophy and dilate after MI.

Compensatory hypertrophy can initially maintain hemodynamic performance.

Excess dilation increases oxygen demand and can aggravate ischemia.

Scar and hypertrophy may stiffen or distort the ventricle, limiting output.

Slide 83 · Long-term outcome and prevention

Residual LV function strongly influences long-term prognosis.

Persistent coronary obstruction in remaining viable myocardium is also important.

Risk-factor control before an initial MI is primary prevention.

Preventing reinfarction in survivors is secondary prevention.

Slide 84 · Clinicopathologic integration: A time sequence

Minutes: Contractile dysfunction can precede myocyte necrosis.

Hours: Sarcolemmal disruption precedes detectable biochemical markers.

Days 1–3: Neutrophilic inflammation becomes prominent.

Days 3–7: Weakening during macrophage clearance predisposes to rupture.

Weeks: Collagenous replacement produces a permanent scar.

Slide 85 · Core distinctions to retain

Reversible ischemic dysfunction versus irreversible myocyte necrosis.

Transmural versus subendocardial versus multifocal microinfarction.

Restored epicardial flow versus inadequate microvascular reperfusion.

Early rupture of softened myocardium versus late scar aneurysm.