Mechanical Mechanisms for Thrombosis in Microvessels Qin Liu 1 , David Mirc 2 , and Bingmei Fu 1 1 Department of Biomedical Engineering, the City College of New York, the City University of New York, New York, NY10031 2 Department of Mechanical Engineering, University of Nevada-Las Vegas, Las Vegas, NV 89154 Abstract–The hypothesis that thrombus can be induced in curved vessels due to mechanical stimuli was tested both experimentally and computationally. Our in vivo experiments on rat mesentery showed that thrombi could be formed in non-injured stretched/curved microvessels (post-capillary venules, 20-50 micrometer in diameter), and they were initiated at the inner side of the curvature. To investigate the mechanical mechanisms of the thrombus formation, we performed 3-D computational simulation using commercial software, FLUENT. Vessels with different curvatures (90 o and 180 o ) as well as different shaped-cross sections (circular and elliptic) were considered. Our computational results demonstrated that the shear rate and shear rate gradient at the inner side of the curve were higher than those at the opposite side. The differences became larger in more bended and elliptic-shaped microvessels. This suggested that higher shear rate and shear rate gradient are two of the factors that initiate the thrombosis in curved post-capillary venules. Our results are consistent with others in branched venules [1]. I. INTRODUCTION It has been found that physical factors alone, without exogenous chemical factors, can induce platelet aggregation near an injured/damaged location in the vessel. These physical factors are related to the magnitude of shear stress/rate, the local geometry of the vessel, and the duration of the forces applied [2]. Study [1] on microvessels (arterioles/venules) of rat mesentery showed that thrombus initiation depended significantly on shear rate rather than the flow velocity. Platelet thrombi were first initiated at locations of higher shear rate in venules and lower shear rate in arterioles. While in previous studies, either there is turbulence or slowing in the flow (flow stasis), or the vessels must be injured/damaged by mechanical, electrical, laser-induced [3] or photochemical methods [4], in the current study, we hypothesized that thrombus could be induced in intact non-injured stretched/curved microvessels due to mechanical stimuli such as localized shear rates. II. MATERIALS Female Sprague-Dawley rats (250-300 g, age 3-4 month) were supplied by Simonson Laboratory (Gilroy, CA). Computational simulation was performed on personal computer (DELL, Pentium 4 CPU, 3.80GHz, 3.37GB RAM). III. METHODS Rat mesentery was gently taken out and arranged on the surface of a polished quartz pillar (2cm in diameter), and was continuously superfused with Ringer solution at 35-37 o C. The microvessel chosen were straight non- branched postcapillary venules (diameters 20-50 μm). Restraining glass pipettes were used to hold and stretch the tissue near the venule to form the curvature. The microvessel was stretched/curved for ~60 min or less. Blood circulation in the microvessel was observed by using a COHU CCD video camera. 3-D models were created with different curvature angles (0 o -straight, 90 o , and 180 o ) as well as different cross sections (circular and elliptic). The models were calculated using Fluent (Fluent Inc., Lebanon, NH). Blood flow was assumed to be steady, incompressible, laminar, and Newtonian with average velocity 1 mm /s. Microvessel wall was assumed to be rigid and impermeable. The density of blood was 1050 kg/m 3 , and viscosity 2.5 cp [5]. Non-slip boundary condition was applied on the wall. The outlet pressure was 980 Pa. The Reynolds number of the flow in the vessel was approximately 0.01. Solution convergence criterion was 10 -8 in magnitude of residuals. 173 1-4244-1033-9/07/$25.00 © 2007 IEEE.