Arterial wall degeneration plus hemodynamic insult cause arterial wall remodeling and nascent aneurysm formation at specific sites in dogs.

To determine whether arterial wall degeneration, in combination with hemodynamic insult, causes cerebral artery aneurysms in a dog model, we simulated the geometry and hemodynamics of a human artery by surgical reconstruction of both common carotid arteries in 12 dogs. The dogs were then randomly assigned to one of the following groups: hemodynamic insult + elastase insult group ( n = 6), hemodynamic insult group (n = 6), or elastase control group (n = 3), in which the straight common carotid arteries were subjected to elastase alone. Angiography and hemodynamic analysis were performed immediately and at 12 weeks after surgery; the animals were then killed for histologic evaluation. The 12 surgically reconstructed distal internal carotid arteries simulated the human artery well with respect to geometric and hemodynamic measurements, with the intended aneurysm sites exposed to higher wall shear stress and velocity, lower pressure, turbulent flow, and changes in wall shear stress gradient. Nascent aneurysms developed in 4 hemodynamic insult + elastase insult group dogs at 12 weeks; blood flow analysis demonstrated decreased wall shear stress, increased pressure, and wall shear stress gradient from the neck to the dome. Arterial wall remodeling or nascent aneurysm formation in the hemodynamic insult + elastase insult group versus the other groups was indicated by internal elastic lamina/elastic fiber disruption, muscular layer thinning, increased smooth muscle cell proliferation, macrophage infiltration, and high expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in the media. These data suggest that nascent aneurysms were caused by the combination of arterial wall degeneration and hemodynamic perturbations in this distal internal carotid artery dog model.