The Cell BiologyThe Cell Biologyof anof an

Episode of Severe IndigestionEpisode of Severe Indigestion

Richard I. Levin, M.D.Richard I. Levin, M.D.Vice Dean for Education, Faculty and Academic AffairsVice Dean for Education, Faculty and Academic Affairs

Professor of MedicineProfessor of MedicineThe Leon H. Charney Division of CardiologyThe Leon H. Charney Division of Cardiology

HistoryHistory6:15 AM, Thursday July 5, 20046:15 AM, Thursday July 5, 2004

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

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

Physical ExaminationPhysical ExaminationA mildly obese woman who seemed in A mildly obese woman who seemed in distress and appeared pale, sweating distress and appeared pale, sweating profuselyprofusely

Pulse:Pulse: 132 132BP:BP: 94/66 94/66Lungs:Lungs: Few rales at the left base Few rales at the left baseHeart:Heart: Soft S1 & S2 Soft S1 & S2Pulses:Pulses: diminished throughout diminished throughout

TPTP

Isoelectric LineIsoelectric Line

STST

STST

TPTP

DiagnosisDiagnosis

Acute, Anterior Wall Acute, Anterior Wall Myocardial InfarctionMyocardial Infarction

(STEMI)(STEMI)

Coronary Coronary AnatomyAnatomy

after Lossnitzerafter Lossnitzer

EtiologyEtiology

Coronary AtherosclerosisCoronary Atherosclerosis

Normal VesselNormal Vessel

1010

What and How?What and How?

1.Exposure to toxins2.Genetic predisposition3.Inflammation

Endothelial Cells Are the Key Endothelial Cells Are the Key To Normal Vessel LifeTo Normal Vessel Life

Endothelial Cell

Endothelial Function in HealthEndothelial Function in Health

• Maintain the blood in a fluid state

• Calm the warrior cells of inflammation

• Balance between dilation & constriction

• Homeostasis

BalletBalletof of

InflammationInflammation

Endothelial Function in Endothelial Function in AtherosclerosisAtherosclerosis

• Promote clotting of the blood

• Excite the warrior cells of inflammation

• Induce vasoconstriction

• Homeostasis

EC Ingest Lipid DropletsEC Ingest Lipid Droplets

Braunwald & Brown ‘96Braunwald & Brown ‘96

Induction of CAMsInduction of CAMs

Inflammation Induced byInflammation Induced byOxidative StressOxidative Stress

OO2 2 InjuryInjury

"N"NORMALORMAL" "

EC

SMC

VV

Leukocytes Leukocytes Adhere to Adhere to

Activated ECActivated EC

Braunwald & Brown ‘96Braunwald & Brown ‘96

Monocyte ActivationMonocyte Activation

2020

2121

2121

Stem Cells

2828

3131

Fifty Years of Fifty Years of InflammationInflammation

after Lossnitzerafter Lossnitzer

CourseCourse

• ThrombolysisThrombolysis

• StentingStenting

t-PA Induces Fibrinolysist-PA Induces Fibrinolysis

PlasminogenPlasminogen

t-PAt-PA

**PlasminPlasmin**

FF IIBBRRIINN

FIBRINFIBRIN

CourseCourse

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

Coronary Coronary AnatomyAnatomy

after Lossnitzerafter Lossnitzer

Angiogram Angiogram of the of the

Occluded Occluded LADLAD

Angiogram Angiogram of the of the

Occluded Occluded LADLAD

Stenting of Stenting of the Occluded the Occluded

LADLAD

Stenting of Stenting of the Occluded the Occluded

LADLAD

Restoration of Normal FlowRestoration of Normal Flow