Angiography in patients with unstable angina or myocardial infarction with subtotal coronary occlusions reveals eccentric stenoses with irregularborders suggesting ruptured atherosclerotic plaques. In addition, the closer the angiogram is to the time of chest pain the higher is the likelihoodof observing a thrombotic filling defect distal to the stenotic region. Thus, we: 1) have investigated the relationship among platelet-vessel wall interaction, rheology, andthrombogenicsubstrate and 2) propose a hypothesisaccounting for thrombosis in the acute coronary syndromes.1) Platelet Vessel Wall Interactions, Rheology and Substrate - We have studied substrate and rheology in both an 'ex vivo' perfusion chamber and 'in vivo'swine model. Qur results, combinedwith those of others, show the following:-Platelet Vessel Wall Interaction and Thrombus Formation - a) In superficial arterial injury plateletsadherevia platelet membrane glycoprotein (GP) lb to the vessel wall to form a monolayer. Von Willebrand Factor (vWF), a high molecular weight glycoprotein found in plasma, platelets, and endothelial cells, binds GPIb and supports platelet adhesion. Platelet derived growth factors(PDGF) from these adherent platelets may contribute to atherogenesis. b) In deep arterial injury, plateletsare stimulated by three pathways -arachidonate, ADP and the "third pathway" -leading to exposure of platelet receptors (GPIIb/IIIa), and subsequent aggregation. Fibrinogenand vWF participate in aggregation bybinding to GPIIb/IIIa. Simultaneously, thrombin stimulates aggregation andthe formation of fibrin that stabilizes platelet aggregates, c) Both a platelet monolayer and aggregation with thrombosis, produce vasoconstriction due to release of platelet products (serotonin, thromboxane A2,and PDGF).- Rheology - a) Stenotic lesions produce a high local shear rate, whichenhances platelet-vessel wall interaction and, in the presence of acute rupture, platelet deposition and subsequent thrombus formation, b) Platelet deposition and thrombosis are particularly favored if the site of rupture includes the stenosis with its high shear rate,while the stasis in the post-stenotic region favors proprogationof thrombus.- Substrate - a) Plaque rupture produces a rough surface and exposes collagen and fat to flowing blood. Thisstimulates mural thrombosis, b) Such thrombus is either fixed or labile depending on the degree of plaque rupture or damage.2) Acute and Subacute Coronary Syndromes - The above observations in the swine model, coupled with recent clinical and pathological observations support the following:-Unstable Angina - Mild or restricted plaque rupture with or without activated mural thrombus, by increasingthe stenosis, explains the increase in exertional angina; subsequent labile thrombosis with platelet-related vasoconstriction explains the resting angina.-Q Wave Myocardial Infarction - The thrombus is occlusive and fixed or persistent because the damage to the vessel wall or to the plaque is more severe or extensive than in unstable angina.-Non-Q Wave Myocardial Infarction -In this syndrome, intermediate between unstable angina and Q wave myocardial infarction, the occlusive thrombus is more transient than in Q wave infarction because of less substrate exposure or damage.
Plaque disruption and the acute coronary syndromes of unstable angina and myocardial infarction: If the substrate is similar, why is the clinical presentation different?
