1. The Cell Biology of an Episode of Severe Indigestion Richard I. Levin, M.D. Vice Dean for Education, Faculty and Academic Affairs Professor of Medicine The Leon H. Charney Division of Cardiology

2. History 6:15 AM, Thursday July 5, 2004 A 46 year old woman with a history of terrible indigestion since her teens came to the ER complaining of a severe episode. It was present when she awakened, unexpectedly early, at 4:45 AM and did not respond to sitting up or taking anatacids. This was the first time that those actions did not ameliorate the pain.

3. History Continued Last evening, she celebrated the engagement of her first son and had too much red wine and spicy food. Earlier that day she had helped her husband rake leaves in the yard, the most exertion she had had in months. The pain was described as her typical burning pain in the retrosternal area, perhaps a little more intense and she thought she felt it in the back of her jaw as well.

4. Physical Examination A mildly obese woman who seemed in distress and appeared pale, sweating profusely Pulse: 132 BP: 94/66 Lungs: Few rales at the left base Heart: Soft S1 & S2 Pulses: diminished throughout

5. TP Isoelectric Line ST ST TP

6. Diagnosis Acute, Anterior Wall Myocardial Infarction (STEMI)

8. Etiology Coronary Atherosclerosis

9. Normal Vessel

10. 10

11. What and How? 1. 1.Exposure to toxins 2. 2.Genetic predisposition 3. 3.Inflammation

12. Endothelial Cells Are the Key To Normal Vessel Life Endothelial Cell

13. Endothelial Function in Health Maintain the blood in a fluid state Calm the warrior cells of inflammation Balance between dilation & constriction Homeostasis

14. Ballet of Inflammation

15. Endothelial Function in Atherosclerosis Promote clotting of the blood Excite the warrior cells of inflammation Induce vasoconstriction Homeostasis

17. EC Ingest Lipid Droplets Braunwald & Brown ‘96

18. Inflammation Induced by Oxidative Stress O 2 Injury EC SMC VV

19. Leukocytes Adhere to Activated EC Braunwald & Brown ‘96

20. Monocyte Activation

21. 20

22. 21

24. 21

25. 28

26. 31

27. Fifty Years of Inflammation

28. Course ThrombolysisThrombolysis StentingStenting

29. t-PA Induces Fibrinolysis Plasminogent-PA *Plasmin* F I B R I N FIBRIN

30. Course Patient taken to catheterization laboratory for angiography and possible PCI (percutaneous coronary intervention)

32. Angiogram of the Occluded LAD

34. Stenting of the Occluded LAD

36. Restoration of Normal Flow