A PERFUSION CHAMBER DEVELOPED TO INVESTIGATE THROMBUS FORMATION AND SHEAR PROFILES IN FLOWING NATIVE HUMAN BLOOD AT THE APEX OF WELL-DEFINED STENOSES

The precipitating event leading to stroke, myocardial infarction, and/ or sudden death may be related to the formation of mural thrombus at t he site of a ruptured or superficially damaged stenotic plaque. The fl uid dynamic properties at atherosclerotic plaques that may be implicat ed in this thrombus formation have been described in a wide variety of model systems in both the process of plaque rupture and the growth of platelet thrombi. In general, the local fluid dynamic conditions are complex and show major variations from flow in well-defined laminar fl ow systems. However, no studies have attempted to quantify the effect of stenosis-related disturbances on thrombus formation in native human blood and to compare them with the local fluid dynamics. We developed a parallel-plate perfusion chamber device in which thrombus formation is measured at the ''apex'' of eccentric stenoses and have correlated such measurements with values of the local fluid dynamics obtained by computer simulation. The extent of stenoses (reduction in the cross-s ectional area of the blood flow channel) was 60%, 80%, and 89%, corres ponding to ''apex'' wall shear rates of 2600, 10 500, and 32 000 sec(- 1) respectively. The wall shear rate in the laminar flow region proxim al and distal to the stenoses was 420 sec(-1). The surface of the sten osis was purified collagen type III fibrils that were exposed to flowi ng nonanticoagulated human blood drawn directly from an antecubital ve in by a pump placed distally to the perfusion chamber. The resulting b lood-collagen interactions were quantified by light microscopy by usin g a morphometric image analysis technique. Under all conditions studie d, platelet thrombus formation at the ''apex'' was extensive. Thrombi that formed at the two highest shear conditions (10 500 and 32 000 sec (-1)) showed significant fibrin deposition in lamellae that were surro unded by densely packed platelets. Most of the platelet boundaries wer e diffuse and difficult to recognize. The direct adhesion of platelets to the collagen surface was greatest at 2600 sec(-1) but dropped at t he higher shear rates (P<.02). In contrast, the thrombus volume increa sed steadily with increasing shear but decreased considerably at 32 00 0 sec(-1) (P<.004). The general increase in fibrin formation at shear rates of 10 500 sec(-1) and above and the reduction in thrombus volume at 32 000 sec(-1) have not been previously reported and are in contra st with their dependence on shear conditions noted at lower shear rate s (110 500 sec(-1)). Mechanisms of thrombosis at conditions typical of advanced arteriosclerotic lesions may therefore be altered from those observed under physiological flow.