This presentation was prepared by Dr. Viduranga Edirisinghe; upon request made by the board certified Consultant Cardiologist, Dr.(Mrs). Nimali Fernando, MD

1. Pathogenesis of ACSs

2. ACSs
• May result from new superimposed
thrombosis on a pre-existing ("fixed")
atherosclerotic occlusion and/or vasospasm of
one or more coronary arteries.

3. Role of Acute Plaque Changes
• In most patients, unstable angina, infarction,
and many cases of SCD all occur because of
abrupt plaque change followed by thrombosis.
• Hence the term acute coronary syndrome.

4. Acute Plaque Changes
Highly thrombogenic
plaque constituents
Rupture, fissuring, or
Exposing
ulceration
Underlying
subendothelial
basement membrane
Acute Coronary
Syndromes
Worsening of the
luminal occlusion
Hemorrhage into the Expansion of plaque
core of plaques volume
Plaque rupture

6. Events that trigger the abrupt plaque
changes
• Rupture reflects the inability of a plaque to
withstand mechanical stresses.
• Triggers may be intrinsic or extrinsic
Intrinsic factors Extrinsic factors
• Large atheromatous • Adrenergic stimulation
core • Intense emotional stress
• Thickness of the fibrous
cap

7. Integrity of the Plaque
Fibrous caps are continuously remodeling
collagen collagen
synthesis degradation
Collagen produced  by smooth muscle cells
Collagen degraded  by the action of metalloproteinases (macrophages)

8. Role of Inflammation
• Inflammation plays an essential role at all
stages of atherosclerosis
• What’s the contribution of Inflammation to
acute coronary syndromes…?
Breakdown of Plaque
Neutrophil Release of
Inflammation collagen in the destabilization &
infiltration metalloproteinases
fibrous cap rupture

9. Role of Thrombus
• Formation of a thrombus on a disrupted
atherosclerotic plaque
• Significant rapid stenosis
• Complete occlusion of the coronary arteries
• Mural thrombus in a coronary artery can also
embolize
• Small fragments of thrombotic material
• Small infarcts

10. Acute Myocardial Infarction
• Ischemic necrosis of a part of the myocardium
• In a typical MI,
A sudden disruption of an atheromatous plaque
Platelets adhere, aggregate, become activated
Release potent secondary aggregators(thromboxane A2, adenosine diphosphate, and serotonin)
Other mediators activate the extrinsic pathway of coagulation
Vasospasm (platelet aggregation and mediator release)
Within minutes the thrombus can evolve to completely occlude the coronary lumen of the coronary vessel

11. Acute Myocardial Infarction
Electrical instability of the Arrhythmias (ventricular
myocardium fibrillation)
Ischemia Death of myocardium
Or a fatal mechanical failure
Reduction in the contractility of
the myocardium
Reduction in the ejection fraction
& increase in end systolic volume
& pressure (Heart failure)

12. • Irreversible injury of ischemic myocytes first
occurs in the subendocardial zone (STEMI)
• With more prolonged ischemia
• Involve progressively more of the transmural
thickness (NSTEMI)

13. Myocardial Infarction