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.
OBJECTIVE
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.


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.
From the Department of Diagnostic and Interventional Radiology (J.W., H.-Q.T., Y.-Q.Z., M.-H.L., L.Y., Y.-S.C.), Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
J
J
Wang
From the Department of Diagnostic and Interventional Radiology (J.W., H.-Q.T., Y.-Q.Z., M.-H.L., L.Y., Y.-S.C.), Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
H-Q
HQ
Tan
From the Department of Diagnostic and Interventional Radiology (J.W., H.-Q.T., Y.-Q.Z., M.-H.L., L.Y., Y.-S.C.), Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China zhuyueqi@hotmail.com liminghuaradio@hotmail.com.
Y-Q
YQ
Zhu
From the Department of Diagnostic and Interventional Radiology (J.W., H.-Q.T., Y.-Q.Z., M.-H.L., L.Y., Y.-S.C.), Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China zhuyueqi@hotmail.com liminghuaradio@hotmail.com.
M-H
MH
Li
School of Mechanical Engineering (Z.-Z.L.), Shanghai Jiao Tong University, Shanghai, China.
Z-Z
ZZ
Li
From the Department of Diagnostic and Interventional Radiology (J.W., H.-Q.T., Y.-Q.Z., M.-H.L., L.Y., Y.-S.C.), Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
L
L
Yan
From the Department of Diagnostic and Interventional Radiology (J.W., H.-Q.T., Y.-Q.Z., M.-H.L., L.Y., Y.-S.C.), Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Y-S
YS
Cheng
D000818:Animals; D017536:Carotid Artery, Common / Q000378:metabolism / Q000473:pathology*; D002533:Cerebral Angiography; D004195:Disease Models, Animal; D004285:Dogs; D006439:Hemodynamics / Q000502:physiology*; D002532:Intracranial Aneurysm / Q000378:metabolism / Q000473:pathology*; D013314:Stress, Mechanical