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

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.

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.

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

TP Isoelectric Line ST ST TP

Diagnosis Acute, Anterior Wall Myocardial Infarction (STEMI)

Etiology Coronary Atherosclerosis

Normal Vessel

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

Endothelial Cells Are the Key To Normal Vessel Life Endothelial Cell

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

Ballet of Inflammation

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

EC Ingest Lipid Droplets Braunwald & Brown ‘96

Inflammation Induced by Oxidative Stress O 2 Injury EC SMC VV

Leukocytes Adhere to Activated EC Braunwald & Brown ‘96

Monocyte Activation

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Fifty Years of Inflammation

Course ThrombolysisThrombolysis StentingStenting

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

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

Angiogram of the Occluded LAD

Stenting of the Occluded LAD

Restoration of Normal Flow