Circulation, Vol 90, 988-996, Copyright © 1994 by American Heart Association
A Mailhac, JJ Badimon, JT Fallon, A Fernandez-Ortiz, B Meyer, JH Chesebro, V Fuster and L Badimon
BACKGROUND: Coronary thrombosis is a dynamic process dependent on the
pathological substrate, the local shear forces, and blood factors. METHODS
AND RESULTS: We investigated the effect of a severe (80%) eccentric
stenosis on fibrin(ogen) interaction with a deeply damaged vessel wall, its
relation to platelet deposition in thrombus formation, and the influence of
time on thrombus growth. Porcine 125I-fibrinogen and autologous
111In-platelets were injected into pigs instrumented for extracorporeal
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 chamber containing
an eccentric axisymmetric sinusoidal stenosis obstructing 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 flow perfused segments one to
two orders of magnitude greater at the apex of the stenosis. Fibrin(ogen)
deposition, its axial distribution with respect to the apex, and its
relation to platelet deposition were determined 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 the studied perfusion times (P <
.02). However, fibrin(ogen) deposition demonstrated a significantly smaller
degree of increase from the prestenotic 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 either low or high shear rate. The rate of
platelet deposition was relatively 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 stenosis 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 pattern is not influenced by time. Finally,
fibrin(ogen) deposition appears to be predominant in the thrombus layers
adjacent to a severely damaged vessel wall regardless of the local shear
stress levels and flow conditions.
ARTICLES
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
Cardiovascular Biology Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston.
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