Mouse Vein Graft Hemodynamic Manipulations to Enhance Experimental Utility

Mouse models serve as a tool to study vein graft failure. However, in wild-type mice, there is limited intimal hyperplasia, hampering efforts to identify anti-intimal hyperplasia therapies. Furthermore, vein graft wall remodeling has not been well quantified in mice. We hypothesized that simple hemodynamic manipulations can reproducibly augment intimal hyperplasia and remodeling end points in mouse vein grafts, thereby enhancing their experimental utility. Mouse inferior vena cava-to-carotid interposition isografts were completed using an anastomotic cuff technique. Three flow restriction manipulations were executed by ligating outflow carotid branches, creating an outflow conunon carotid stenosis, and constructing a midgraft stenosis. Flowmetry and ultrasonography were used perioperatively and at day 28. All ligation strategies decreased the graft flow rate and wall shear stress. Morphometry showed that intimal thickness increased by 26% via carotid branch ligation and by 80% via common carotid stenosis. Despite similar mean flow rates and shear stresses among the three manipulations, the flow waveform amplitudes were lowest with common carotid stenosis. The disordered flow of the midgraft stenosis yielded poststenotic dilatation. The creation of an outflow common carotid stenosis generates clinically relevant (poor runoff) vein graft low wall shear stress and offers a technically flexible method for enhancing the intimal hyperplasia response. Midgraft stenosis exhibits poststenotic positive wall remodeling. These reproducible approaches offer novel strategies for increasing the utility of mouse vein graft models. (Am J Pathol 2011, 178:2910 2919; DOI: 10.1016/j.ajpath.2011.02.014)