EFFECT OF AN ECCENTRIC SEVERE STENOSIS ON FIBRIN(OGEN) DEPOSITION ON SEVERELY DAMAGED VESSEL WALL IN ARTERIAL THROMBOSIS - RELATIVE CONTRIBUTION OF FIBRIN(OGEN) AND PLATELETS

Background Coronary thrombosis is a dynamic process dependent on the p athological substrate, the local shear forces, and blood factors. Meth ods and Results We investigated the effect of a severe (80%) eccentric stenosis on fibrin(ogen) interaction with a deeply damaged vessel wal l, its relation to platelet deposition in thrombus formation, and the influence of time on thrombus growth. Porcine I-125-fibrinogen and aut ologous In-111-platelets were injected into pigs instrumented for extr acorporeal circulation and treated with low-dose heparin (aPTT ratio < 1.5) that has been previously shown and herein confirmed not to affect platelet and/or fibrin(ogen) attachment. Tunica media, as a model of severely injured vessel wall, was mounted in a tubular perfusion chamb er containing an eccentric axisymmetric sinusoidal stenosis obstructin g the lumen and exposed for 1, 5, and 10 minutes to perfusing blood. A shear rate of 424 s(-1) at the laminar, parallel parabolic local how perfused segments one to two orders of magnitude greater at the apex o f the stenosis. Fibrin(ogen) deposition, its axial distribution with r espect to the apex, and its relation to platelet deposition were deter mined by an ex vivo analysis of the test substrates. Fibrin(ogen) and platelet deposition were both significantly higher at the apex of the stenosis than at either the prestenotic or poststenotic area at all th e studied perfusion times (P<.02). However, fibrin(ogen) deposition de monstrated a significantly smaller degree of increase from the presten otic area to the apex as well as a smaller degree of decrease from the latter to the poststenotic region, compared with platelet deposition (P<.05). Although both fibrin(ogen) and platelet deposition increased over time, the ratio of fibrin(ogen) to platelets showed a progressive decrease that became significant from 5 to 10 minutes (P<.03) at eith er low or high shear rate. The rate of platelet deposition was relativ ely constant; however, fibrin(ogen) deposition progressively decreased , especially at the apex. Conclusions On severely damaged vessel wall, fibrin(ogen) and platelet deposition is maximal at the apex of the st enosis where shear rate is extremely high and parallel streamlines are deformed. Nevertheless, fibrin(ogen) deposition is significantly less dependent on high shear rate than is platelet deposition, and the pat tern is not influenced by time. Finally, fibrin(ogen) deposition appea rs to be predominant in the thrombus layers adjacent to a severely dam aged vessel wall regardless of the local shear stress levels and flow conditions.