Ductus arteriosusBlood from L pulmonary artery aorta during intrauterine life

Closes in first 48 hours of lifeOxygenated bloodDecreased pulmonary resistance to flowDecreased PGE2 levels

Ligamentum arteriosum

PDA : clinical 7% of congenital heart defects (90% are isolated defects) Hypoxia associated Machinery murmerPressure problems EisenmengerEndocarditis

PGE inhibitors Rx (BUT not if ?)

Prostaglandin E preserves patency

Ischemic Heart Disease

Ischemic Heart DiseaseInsufficient blood flow to myocardium Leading cause of death in US

90% + Atherosclerosis Coronary obstruction

Starts to build up in early lifePresents clinically in adult life

Ischemic Heart Disease : The other 10%?Increased demand by myocardium Hypertension Low blood volumeShock / HemorrhageDecreased oxygenation Pneumonia / congestive cardiac failureDecreased O2 carrying capacity of bloodAnemia / CO

Classification Angina pectoris

Acute myocardial infarction

Chronic myocardial ischemia

Sudden cardiac death

Epidemiology1 million deaths in US in 1963500K now

Lifestyle changesImproved therapy

BUT may increase again People live longerObesity epidemic

Pathogenesis Narrowing by atherosclerosis+/- Thrombosis +/- Vasospasm

Up to 70% narrowing asymptomatic70% + Stable angina90% + Unstable angina

Coronary remodeling over years? Collateral supply

Atherosclerotic plaque

Histology of atherosclerotic plaque

Factors in Atherosclerosis and IHD1 InflammationInduced by interaction between endothelial cells and PMNs

2. ThrombosisSecondary to plaque rupture

3. VasoconstrictionChemically induced

1. InflammationWBC interaction with endothelium

T cells and macrophages activatedInduce smooth muscle cell proliferation matrix production

Later :Macrophage metalloproteinase releaseDestabilization of plaque

2. ThrombosisPartial occlusion of lumen by plaqueTemporary occlusion ischemiaUnstable angina

Permanent occlusion (or delayed fibrinolysis) infarct

Thrombi may embolize to block distal vessel Microinfarcts

3. Vasoconstriction Turbulence plaque damage

Circulating adrenergic agonistsPlatlet factors NO entothelin imbalanceDue to Endothelial cell dysfunction Inflammatory cell mediators Within and around plaque

Angina

Stable angina

What causes acute plaque change?Rupture of surface Shear forces act on elevated plaque

Hemorrhage into plaqueSudden enlargementRupture

Structure of mature plaque

Fibrous cap interface with lumen

Central lipid core

Inflammatory interface with media

Fatty streaks

Which plaques are likely to rupture? Weak fibrous cap Few smooth muscle cells (produce collagen)Many Macrophages (produce metalloproteinases)

Which plaques are likely to rupture? 66% of ruptured plaques are

Angina pectorisStable Narrowing of lumen Exercise related, alleviated by rest, Nitroglycerine

PrinzmetalSpasmSpasm related, attacks occur at rest,Alleviated by nitroglycerine, Ca channel blockers

Unstable ThrombosisThrombosis related Pre MIIncreasing frequency, Increasing severity

Unstable anginaMicroinfarcts

Myocardial Infarction

Myocardial Infarction 1.5 million per annum in US0.5 million deaths0.25 million before hospitalization

Risks : Those of AtherosclerosisMale > Female, (to menopause) B = WIncreasing incidence with increasing age10% < 40 yrs 45% < 65 Yrs

Etiology Classification 90% thrombus on atherosclerotic plaque10%

Coronary artery vasospasm Emboli (A Fib or Valve lesion) Increased demand + decreased perfusionExtensive narrowing Small vessel damage Vasculitis, amyloid, Sickling

Typical MIThrombus formed on ruptured plaque Platlets + coagulation proteins

In 90% of cases seen within 4 hoursBUT only in 60% at 12 hoursFibrinolysis Rationale for early treatment with tPA

MI sequenceATP not produced, Lactic acid accumulates1 Minute : Functional changeLoss in contractility

Up to 20 mins : Reversible Structural changeGlycogen depletionCell swelling, Mitochondrial swelling

After 20 mins : Irreversible structural changeNecrosis of myocytes

Take away messageTreat early

May see Stunned myocardium Inability to function properly for some time ArrythmiasDue to electrical instability of affected region

MI progression

Early : Subendocardial involvement mainlyMost fragile blood supplyHigh pressure from lumen

Later : Transmural Extends to >50% of wall May take 3 6 hours

Time 0 hrs 2 hrs 24 hrs

Distribution of infarcts

Distribution of infarctsLAD 40 50%Anterior LVAnterior Vent septumApex of heart

LCX 20%Lateral LV wall

WidowmakerBlockage of main LCA

Collateral circulations may be established

Distribution of infarctsRCA 30 40% : Right ventricle

Distribution of infarctsRCA 30 40% : Right ventricle

Posterior descending arteryPosterior septum and LV wall(90%) from RCA(10% from LCX)

Left or Right Dominant?

Left or Right Dominant?

Left and Right dominant hearts Depending on source of Posterior Descending artery

Transmural or Subendocardial?

Transmural or Subendocardial?Transmural Subendocardial

Elevated ST segmentNOSTEMIsNegative Q wavesNOLoss or R wave amplitude

Subendocardial infarcts

Transient local obstruction

Global hypotension

Small vessel disease

Pathology of infarction

Pathology : Gross

No change (< 12hrs)Pallor(- 24 hrs)Increasing pallor (1 - 3 days)

Hyperemic border (4 7 days)Softening, (5 - 10 days)Collagen deposition (2 weeks - months)

MicroscopicNo change (< 4 hours)Necrosis ( 4 hours - )PMNs (24 hours +)Macrophages (3 days +)Fibroblasts (7 days +)

Triphenyl tetrazolium chlorideRedox indicator

Turns red when applied to living cellsRespiratory enzyme intact

Remains white when applied to dead tissueRespiratory enzymes denatured

Lack of triphenyl tetrazolium chloride staining

One-day-old infarct showing coagulative necrosis along with wavy fibers

Dense PMN infiltrate 2- to 3-day

Macrophage phagocytosis (7-10 days).

Granulation tissue loose collagen +++ capillaries

Dense collagenous scar

Reperfusion Injury

Reperfusion injuryOygen free radicals (from PMNs)

Microvascular injury reduced flow

Hemorrhage due to capillary damage

Contraction band necrosis.

Contraction band necrosis

Contraction band necrosisHypercontracted sarcomeres

Calcium cell

Drive actin-myosin interactions

ATP not present to allow relaxation

Clinical aspects : PainSevere, crushing substernal chest painRadiate to left arm, elsewhere20 minutes to several hours Not relieved by nitroglycerin or rest

Silent infarcts (10% to 15%) Diabetes mellitus (peripheral neuropathies) Elderly

Clinical aspects Rapid weak pulse Patients diaphoretic +/- nauseated Dyspnea Impaired myocardial contractilityPulmonary congestion and edemaCardiogenic shock >40% of the LV

EKGQ waves (indicating transmural infarcts)ST-segment abnormalities T-wave inversion (Abnormal in myocardial repolarization)

Arrhythmias SCD

Lab testsTnI and TnT 2 -4 hrs 48 hr peak 7 to 10 days

CK-MB 2 to 4 24 to 48 72 hours

Complications of MI

Complications of MI1960s in-hospital death rate 30% Now 10% - 13% today 7% with aggressive reperfusion therapy

50% deaths occur before arrive at hospitalUsually

Complications of MI (in 75%)Left ventricular failureHypotensionPulmonary congestion / Edema Cardiogenic shock in 10% to 15% (>40% of the left ventricle)70% mortality70% of hospital deathsArrhythmias.

Complications of MI (contd)Rupture. 1- 5% (3 7 days)7% to 25% of deaths from MI

Ventricular free wall (hemopericardium)Ventricular septumPapillary muscle rupture

Complications of MI (contd)Pericarditis Stretching of infarct regionMural thrombus (stasis endothelial damage)Thromboembolism

Ventricular aneurysmPapillary muscle dysfunction Progressive late heart failure

Chronic IHD Ischemic cardiomyopathy

Chronic IHD Ischemic cardiomyopathy

Postinfarction cardiac decompensationGradual loss of ability of healthy myocardium to perfuse body

Without prior infarction (extensive atherosclerosis)

Sudden cardiac death300 to 400K United States

Death from cardiac causesWithout symptoms Within 1 to 24 hours of onset

Sudden cardiac deathVentricular fibrillation Electrical irritability of myocardium distant from the conduction system

Cardioverter defibrillatorsSense and electrically terminate episodes of V Fib

SCD : pathology

90% have 75% coronary stenosis 10 20 % plaque disruption 40% have healed MI

10 20% non-atherosclerotic origin

Non-atherosclerotic causes of SCDSee in younger patients

Hereditary channelopathies Congenital abns of coronary arteries Mitral valve prolapseMyocarditis / sarcoidosisDCM or HCMPulmonary HTMyocardial hypertrophy

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