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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)
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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