PT  - JOURNAL ARTICLE
AU  - J. Wang
AU  - H.-Q. Tan
AU  - Y.-Q. Zhu
AU  - M.-H. Li
AU  - Z.-Z. Li
AU  - L. Yan
AU  - Y.-S. Cheng
TI  - Complex Hemodynamic Insult in Combination with Wall Degeneration at the Apex of an Arterial Bifurcation Contributes to Generation of Nascent Aneurysms in a Canine Model
AID  - 10.3174/ajnr.A3926
DP  - 2014 Sep 01
TA  - American Journal of Neuroradiology
PG  - 1805--1812
VI  - 35
IP  - 9
4099  - http://www.ajnr.org/content/35/9/1805.short
4100  - http://www.ajnr.org/content/35/9/1805.full
SO  - Am. J. Neuroradiol.2014 Sep 01; 35
AB  - BACKGROUND AND PURPOSE: The detailed mechanisms of cerebral aneurysm generation remain unclear. Our aim was to investigate whether specific hemodynamic insult in combination with arterial wall degeneration leads to the development of aneurysms in a canine model. MATERIALS AND METHODS: New branch points in the common carotid artery were created in 18 dogs. Nine animals subsequently received elastase insult at the arterial bifurcation apex (elastase-treated bifurcation group); the control bifurcation group (n = 9) received saline, and 3 dogs received an elastase insult to both straight common carotid arteries (elastase-treated straight group). Angiographic and hemodynamic analysis was performed immediately and 12 and 24 weeks' postsurgery; histologic response was evaluated at 12 and 24 weeks. RESULTS: Angiography revealed nascent aneurysms (mean, 3.2 ± 0.4 mm) at the arterial bifurcation apices in 5/9 models of the elastase-treated bifurcation group (versus 0 in the control bifurcation group and elastase-treated straight group) without any observed aneurysm rupture. Histologic analysis revealed internal elastic lamina discontinuity, elastic fiber disruption, a thinner muscular layer, reduced smooth-muscle cell proliferation, increased inflammatory cell (macrophage) infiltration, and expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in the media of the elastase-treated bifurcation group compared with that in either the control bifurcation group or the elastase-treated straight group (P < .001). Hemodynamic analysis after surgery indicated that the apex experienced extremely low wall shear stress and flow velocity and the highest relative and total pressure in the elastase-treated bifurcation group, while the values returned to normal after arterial wall remodelling. CONCLUSIONS: In our study, combined hemodynamic insult and arterial wall degeneration at arterial bifurcations are required for the generation of aneurysms in a canine model. CBGcontrol bifurcation groupCCAcommon carotid arteryEBGelastase-treated bifurcation groupESGelastase-treated straight groupMAC387antimacrophage antibodyMMPmatrix metalloproteinaseSMCsmooth-muscle cellWSSwall shear stressWSSGwall shear stress gradient