Mechanisms of arterial thrombosis in nonparallel streamlines: platelet thrombi grow on the apex of stenotic severely injured vessel wall. Experimental study in the pig model.

Abstract

The role of thrombosis in various acute coronary syndromes has been established. However, the basic mechanism by which plaque rupture leads to a growing thrombus in the vicinity of stenotic lesions is not well understood. Using a characterized flow chamber in a rheologically controlled system, we have mimicked stenotic vessels and studied for the first time cellvessel wall interaction in nonparallel streamlines. Stenoses ranging from 0 to 80% were produced with stripped tunica media to mimic severe vessel wall damage, and perfused with heparinized flowing blood. This perfusion device was placed within an extracorporeal system in swine, and blood was perfused for selected times from 1 to 30 min. Platelet deposition on the surface was evaluated by " Indium-labeled platelets. As percent stenosis increased, platelet deposition significantly increased (P < 0.001), indicating a shear-induced cell activation. Analysis of the axial distribution of platelet deposition indicated that the apex, and not the flow recirculation zone distal to the apex, was the segment of greater platelet accumulation within 30 min of blood perfusion (P < 0.001). These results also indicate that the severity of the acute platelet response to plaque rupture probably depends on the location of the rupture with relation to the apex of the plaque.

Dissolution of Mural Thrombus by Specific Thrombin Inhibition With r-Hirudin

“…9 We have shown that the rate of platelet deposition on severely damaged wall at high shear rates is characterized by a first-order rate constant. 16 …”

“…Shear conditions at the vessel wall were calculated from the theoretical expression for shear rate given for a newtonian fluid in tube flow. 16 …”

Fluid mechanics of arterial stenosis: Relationship to the development of mural thrombus

“…Studies of blood flow through a stenosis using tunica media as a model for damaged vessel wall (2,16), or collagen-coated shunts, have shown increased platelet adhesion on the apex of a stenosis wherein fluid shear forces and shear-rate dependent diffusion are maximum. However, other studies did not show an increase in deposition with increased shear for noncollagencoated shunts (9), a decrease in platelet deposition onto a Lexan surface in the throat region of the stenosis supplemented by an increase in the downstream recirculation region (20), or a decreased deposition of plate-lets with increased flow rate through a hollow fiber hemodialyzer with canine and human blood (7).…”

Moderate Daily Intake of Red Wine Inhibits Mural Thrombosis and Monocyte Tissue Factor Expression in an Experimental Porcine Model

“…13 Groups ingesting red wine showed the same platelet deposition pattern but with lower growth, suggesting that the reduction in platelet deposition will probably be the result of a passivation effect of red wine in platelets. There is evidence that flavonoids present in red wine inhibit cAMP and cGMP phosphodiesterases, 14 increasing platelet levels of cAMP and cGMP.…”