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032 hossein eftekhari,md

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032 hossein eftekhari,md

  1. 1. HOSSEIN EFTEKHARI,MD  VULNERABLE PLAQUE  ANIMAL MODELS  PERCUTANEOUS CORONARY INTERVENTION
  2. 2. AT THE BEGINNING OF 20thCENTRY,CVD ACCOUNTED FOR LESS THAN 10 PERCENT OF ALL DEATHS WORLD WIDE.AT IT’S END,CVD ACCOUNTED FOR NEARLY HALF OF ALL DEATH IN DEVELOPED COUNTRIES.BY 2020,CVD WILL CLAIM 25 MILLION DEATHS ANNUALLY AND WILL SURPASS INFECTIOUS DISEASE AS THE WORLD’S NUMBER ONE CAUSE OF DEATH AND DISABILITES.
  3. 3. THREE COMPLEMENTARY STRATEGIES TO REDUCE MORBIDITY AND MORTALITY FROM CVD:  Lowering overall burden of CVD risk factors in the entire population through population-wide public health measures (national campaign).  Identifying and targeting high-risk subgroup of population who may benefit from preventive intervention.  Resources can be allocated to acute and chronic treatment and secondary prevention.
  4. 4. VULNERABLE P’s  Vulnerable population  Vulnerable patient  Vulnerable plaque
  5. 5. Vulnerable plaques, vulnerable myocardium, andVulnerable plaques, vulnerable myocardium, and hypercoagulablehypercoagulable state of the blood lead tostate of the blood lead to sudden cardiac death and acute myocardial infarction.sudden cardiac death and acute myocardial infarction. Vulnerable Blood Vulnerable Myocardium Vulnerable Plaque Vulnerable Patient
  6. 6. What causes heart attack?
  7. 7. Mostly it is secondary to acute thrombosis over an underlying vulnerable plaque.
  8. 8. lipid-rich core thrombus cap cap
  9. 9. The vast majority of plaque of disruptions are self-contained and clinically silent.So plaque disruption leading to ACS is not a rule but an exception in a -symptomatic patients with non- obstructing atherosclerosis but contributes to plaque progression and luminal narrowing.
  10. 10.  Culprit Plaque; a retrospective terminology  Vulnerable Plaque; a prospective terminology VulnerablePlaque= FutureC ulprit Plaque Clarification of Terminologies
  11. 11. Vulnerable Plaque The short answer is:
  12. 12. What are vulnerableplaques?
  13. 13. Dangerous forms of atherosclerotic plaques that can rupture or induce thrombosis and lead to critical disruption of blood flow. The short answer is:
  14. 14. Proposed Histopathological and ClinicalProposed Histopathological and Clinical Criteria for Definition of VulnerableCriteria for Definition of Vulnerable PlaquePlaque •• MajorMajor Criteria:Criteria: 1.1. Active Inflammation (Active Inflammation (monocytemonocyte// macrophage infiltration)macrophage infiltration) 2.2. Thin Cap with Large Lipid CoreThin Cap with Large Lipid Core 3.3. Endothelial Denudation with SuperficialEndothelial Denudation with Superficial Platelet AggregationPlatelet Aggregation 4.4. Fissured / Wounded PlaqueFissured / Wounded Plaque
  15. 15. Proposed Histopathological and ClinicalProposed Histopathological and Clinical Criteria for Definition of VulnerableCriteria for Definition of Vulnerable PlaquePlaque •• MinorMinor Criteria:Criteria: 1.1. Superficial Calcified noduleSuperficial Calcified nodule 2.2. Glistening YellowGlistening Yellow 3.3. IntraplaqueIntraplaque HemorrhageHemorrhage 4.4. Critical StenosisCritical Stenosis 5.5. Positive Remodeling?Positive Remodeling?
  16. 16. Plaque Rupture: Definition Structural failure of the fibrocellular cap11 that separates an atheromatous core22 from the lumen of an atherosclerotic artery (ie, lumen ↔ core). 11 cap defectcap defect//gapgap rupture, fissure, break, tear not just missingnot just missing endotheliumendothelium 22 lipidlipid--richrich Greek athere, gruel (soft) Propensity to rupture  lipidlipid--richrich corecore + → +++ no coreno core →→ no capno cap -
  17. 17. Plaque Rupture
  18. 18. Ruptured Plaques (~70%) 1. Stenotic (~20%) 2. Non-stenotic (~50%) Non-ruptured Plaques (~ 30%) 1. Erosion (~20%) 2. Calcified Nodule (~5%) 3. Others / Unknown (~5%) Plaque Pathology Responsible for Coronary Thrombotic Death In summary:
  19. 19. Vulnerable Plaque and Vulnerable Patient, The Challenge of Cardiovascular Medicine in 21st Century An introductory tutorial from VP.org In conjunction with The Center for Vulnerable Plaque Research University of Texas Houston and Texas Heart Institute
  20. 20. Ideal method for screeningIdeal method for screening vulnerable plaque/patientvulnerable plaque/patient  NonNon--invasiveinvasive  InexpensiveInexpensive  AccurateAccurate  Widely ReproducibleWidely Reproducible
  21. 21. Emerging Techniques for Detection of Vulnerable Plaque
  22. 22. Emerging Diagnostic Techniques A. Invasive Techniques Angioscopy Intravascular Ultrasound (IVUS) Intravascular T hermography Intravascular Optical CoherenceT omography (OC T ) Intravascular E lastography Intravascular and T ransesophageal MRI Intravascular Nuclear Imaging Intravascular E lectrical ImpedanceImaging Intravascular T issueDoppler Intravascular Shear Stress Imaging Intravascular (Photonic)Spectroscopy
  23. 23. - Raman Spectroscopy - Near-Infrared Diffuse Reflectance Spectroscopy -Fibrousis and lipid measurement -pH and lactate measurement - Fluorescence Emission Spectroscopy - Spectroscopy with contrast media … Invasive Techniques Intravascular (Photonic) Spectroscopy Intra-coronary assessment of endothelial function Intra-coronary measurement of MMPs and cytokines
  24. 24. Emerging Diagnostic Techniques B. Non-Invasive Techniques: A. MRI 1- MRI without contrast media 2- MRI with contrast media: Gadolinium-DPTA 2- MR Imaging of Inflammation: Super Paramagnetic Iron Oxide (SPIO and USPIO) 3- MR Imaging of Thrombosis using monoclonal Ab B. Electron Beam Tomography (EBT) C. Multi-Slice Fast Spiral / Helical Computed Tomography D. Nuclear Imaging (18-FDG, MCP-1, Annexin V, CD40)
  25. 25. Emerging Diagnostic Techniques C. Blood Tests / Serum Markers - CRP - ICAM-1, VCAM, p-Selectin, sCD40-L - Proinflamatory cytokines - Lp-PLA2 - Ox-LDL Ab - PAPP-A D. Endothelial Function Test -Intra coronary acethylcholine test -Noninvasive flow mediated dilatation of brachial artery - Anti-body against endothelial cells
  26. 26. CONCLUSION It is well established that composition and size of lipid core,composition and thickness of fibrous cap, inflammatory process,and the quantity of SMC’s within a plaque are predictors of plaque rupture.
  27. 27. ANIMAL MODELS FOR EXPERIMENTAL STUDIES
  28. 28. THE IMPORTANCE OF ANIMAL MODEL Animal models are important to research directed toward better understanding of human atherosclerosis.For this reason much effort has been expended to identify and characterize species suitable as animal model.
  29. 29. Criteria needed for choosing animal model Susceptibility under standard system of husbandry Ready availability at reasonable cost Ready trainability and size adequate for all project lab procedure Recognition that behavior responses to experimental situations may determine result
  30. 30. The ideal animal model of human atherosclrosis: *Should be easy to acquire and maintain at reasonable cost *Easy to handle *Proper in size *Should be reproducible in lab *Should have well-defined genetic characteristics *Should share with human the most important aspect of disease
  31. 31. THE CHICKEN AS A MODEL *The chicken is good animal model for atherosclerosis study because it is:  Omnivorous  Small and suitable for prolonged lab investigation  Able to develop spontaneous atherosclerosis  Capable of producing atherosclerosis after cholesterol feeding  Plasma level of cholesterol and triglyceride are similar to those in human  Lipid composition of LDL , HDL and chylomicron resemble those in human  There is no essential difference between vascular lesion in chicken on high cholesterol
  32. 32. DISADVANTAGES OF CHICKEN Nonmammals Lesion site inconsistent Complication uncommon Intramyocardial coronary involvement Chicken herpes virus can be the sources of variability
  33. 33. THE PIG AS A MODEL * Some similarities between man and pig in atherosclerosis:  Atherosclerosis in man and pigs develops most frequently in aorta,coronary and intracranial arteries  The age at which lesion originate and the rate of progression in any lesion is independent of other  The origin and distribution of coronary artery in man and pig corresponds closely  The histological change of growth and aging that leads to atherosclerosis of aorta and coronary artery are closely similar  According to the mean age of death and its relation to morphological character and size of lesion,the sequel of atherosclerosis in man and pig also correspond closely
  34. 34. MOUSE AS A MODEL *As a species the mouse is highly resistant to atherosclerosis.But through induced mutation lines of mice have been developed to be susceptible to atherosclerosis,such as:  Mice that are deficient in apoE  Mice that are deficient in LDL receptor  Transgenic mice that express human apoE  Transgenic mice with transdominant mutant form of apoE
  35. 35. pathology Comparison of atherosclerosispathology Comparison of atherosclerosis ApoE-deficient mouse Human Fatty streak with MAC and Tcells yes yes Fibrous plaque with SMC yes yes Lesion calcification yes yes Oxidized apitopes present yes yes Lesions at branches and sites with disturbed flow yes yes Diet responsiveness yes yes Aneurysms observed yes yes Plaque rupture no yes
  36. 36. NO PLAQUE RUPTURE IN ANIMAL MODEL Atherosclerosis plaque rupture is the main cause of coronary thrombosis and MI but currently,there is no animal model of plaque disruption ?
  37. 37. THE POTENTIAL CAUSE OF LACK OF PLAQUE RUPTURE IN MICE May be due to small diameter of mice aorta (<1mm) which increase surface tension preventing plaque rupture
  38. 38. RABBIT AS AN ANIMAL MODEL Advantages: Lesion well characterized Lesion inducible with dietary cholesterol Reproduce rapidly Relatively inexpensive
  39. 39. RABBIT AS AN ANIMAL MODEL Disadvantages: Whole body cholesterol is different from human Lesions don’t duplicate many important features of human Lesions usually occur in aortic arch and thoracic aorta Distribution of coronary artery lesion is different from human(proximal portions aren't involved) Only proximal portion of carotid artery usually involved and cerebral vessels spare
  40. 40. AN EXPERIMENTAL MODEL OF PLAQUE RUPTURE  In rabbit model embedding inflatable balloon in to the atherosclerotic plaque and measuring the pressure needed to inflate the plaque-covered balloon may be an index of plaque mechanical strength

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