In vitro model for studying the effects of hemodynamics on device induced thromboembolism in human blood

Biomateria related thromboembolism is a complex phenomenon, affected by such variables as biomaterial surface chemistry, hemodynamics, and individual donor variations. Thus, isolation of the individual variables would greatly facilitate the understanding and inhibition of this phenomenon. A low volume in vitro model with this potential has been developed, with the initial focus on studying the influence of hemodynamics on thromboembolism (TE) in human blood. Patterned after a larger in vitro model for bovine blood used successfully in our laboratory, the smaller model directed fresh human blood in a single pass through 1/32 inch ID PVC tubing and a flow cell at 3 ml/min. The flow cell consisted of alternating abrupt expansions and contractions of cylindrical tubing that could be modified to study the effects of hemodynamic parameters on TE. Thrombus growth in the flow cell was monitored visually by transillumination microscopy. Emboli from the flow cell were detected continuously by a light-scattering microemboli detector (LSMD), and their strength was assessed by using the constant-pressure filtration (CPF) method. Preliminary studies confirmed the potential of this model. Thrombi were observed visually in the flow cell at sites of high vorticity and at flow separation and reattachment points and were also observed to embolize. Emboli were detected by the LSMD downstream of the flow cell in significantly greater numbers than upstream and were coincident with the embolization of thrombi observed visually. Emboli collected downstream of the flow cell occluded the CPF filters at 50 mm Hg, suggesting that they possessed sufficient strength to occlude microvessels. This model may be used to aid in developing a computer model of thromboembolism, which could subsequently be refined with clinical data.