Kadirvel, Ramanathan

Computational fluid dynamics (CFD) studies provide a valuable tool for evaluating the role of hemodynamics in vascular diseases such as cerebral aneurysms and atherosclerosis. However, such models necessarily only include isolated segments of the vasculature. In this work, we evaluate the influence of geometric approximations in vascular anatomy on hemodynamics in elastase induced saccular aneurysms in rabbits. One representative high aspect ratio (AR—height/neck width) aneurysm and one low AR aneurysm were created at the origin of the right common carotid artery in two New Zealand white rabbits. Three-dimensional (3D) reconstructions of the aneurysm and surrounding arteries were created using 3D rotational angiographic data. Five models with varying extents of neighboring vasculature were created for both the high and low AR cases. A reference model included the aneurysm sac, left common carotid artery (LCCA), aortic arch, and downstream trifurcation/quadrification. Three-dimensional, pulsatile CFD studies were performed and streamlines, wall shear stress (WSS), oscillatory shear index, and cross sectional velocity were compared between the models. The influence of the vascular domain on intra-aneurysmal hemodynamics varied between the low and high AR cases. For the high AR case, even a simple model including only the aneurysm, a small section of neighboring vasculature, and simple extensions captured the main features of the steamline and WSS distribution predicted by the reference model. However, the WSS distribution in the low AR case was more strongly influenced by the extent of vasculature. In particular, it was necessary to include the downstream quadrification and upstream LCCA to obtain good predictions of WSS. The findings in this work demonstrate the accuracy of CFD results can be compromised if insufficient neighboring vessels are included in studies of hemodynamics in elastase induced rabbit aneurysms. Consideration of aspect ratio, hemodynamic parameters of interest, and acceptable magnitude of error when selecting the vascular domain will increase reliability of the results while decreasing computational time.

Contamination of arsenic in drinking water is associated with several human diseases including cancer. It has been reported that oxidative stress plays a vital role in arsenic-induced biochemical and molecular alterations. The aim of the present study was to improve the understanding of arsenic-induced oxidative damage to proteins and to DNA and the role of antioxidants such as ascorbic acid and α-tocopherol in alleviating arsenic-induced damages in experimental rats. A significant increase in the levels of protein oxidation, DNA strand breaks, and DNA–protein cross-links was observed in blood, liver, and kidney of rats exposed to arsenic (100 ppm in drinking water) for 30 days. Co-administration of ascorbic acid and α-tocopherol to arsenic-exposed rats showed a substantial reduction in the levels of arsenic-induced oxidative products of protein and DNA. The results of this study support that free radical–mediated toxic manifestations of arsenic and also suggest that ascorbic acid and α-tocopherol supplementation can improve the arsenic-induced molecular alterations.

Background and Purpose— Even though endovascular coils have been widely used for the treatment of intracranial aneurysms, the cellular and molecular responses of aneurysms to the coils after embolization remain poorly understood. The aim of the present study was to understand the mechanism of apoptosis in aneurysms embolized with platinum coils in the rabbit model of elastase-induced aneurysms. Methods— Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery in 30 rabbits. Aneurysms were allowed to mature for 8 weeks, after which 20 aneurysms were embolized with platinum coils by endovascular means. After 2 (n=10) and 4 (n=10) weeks of implantation, aneurysm samples harboring coils were harvested for apoptotic studies. The remaining 10 uncoiled aneurysms were used as controls; additional controls included the left common carotid artery, which had not undergone any surgical procedure. Control samples were harvested at 12 weeks after aneurysm creation. Results— Expression of procaspases-3, -8, and -9 was elevated in coiled aneurysms embolized with platinum coils at both time points when compared with uncoiled aneurysms and the left common carotid artery. Cleaved caspases-3, -8, and -9 were found to be expressed only at 4 weeks after embolization. Cells within the aneurysm cavity were terminal dUTP nick end-labeling–positive at 4 weeks only. These apoptotic cells were identified as smooth muscle actin–positive cells. Expression of tumor necrosis-α was high in coiled aneurysms when compared with controls. There was no significant difference in the expression of Fas ligand among groups. Decreased expression of antiapoptotic proteins Bcl-2 and phospho-Bad, as well as increased expression of proapoptotic proteins Bax and Bid, was observed in coiled aneurysms at both time points. Conclusions— Activation of apoptosis in aneurysms after embolization with platinum coils is induced by both tumor necrosis factor-α–mediated extrinsic and Bcl-2-mediated intrinsic pathways.

Background and Purpose— We report a preclinical study of a new endoluminal device for aneurysm occlusion to test the hypothesis that the device, even without use of intrasaccular coil placement, could occlude saccular aneurysms without causing substantial parent artery compromise or compromise of adjacent, small branch arteries. Methods— The Pipeline Neuroendovascular Device (Pipeline NED; Chestnut Medical Technologies, Inc) is a braided, tubular, bimetallic endoluminal implant aimed at occlusion of saccular aneurysms through flow disruption along the aneurysm neck. The device was implanted across the necks of 17 elastase-induced aneurysms in the New Zealand white rabbit model and followed for 1 month (n=6), 3 months (n=5), and 6 months (n=6). In each subject, a second device was implanted in the abdominal aorta to cover the origins of lumbar arteries. Aneurysm occlusion rates by angiography (grade 1, complete occlusion; grade 2, near-complete occlusion; and grade 3, incomplete occlusion) were documented. Percent area stenosis of the parent arteries was calculated. Presence of distal emboli in the downstream vessels in the parent artery and branch artery stenosis or occlusion was noted. Results— Grades 1, 2, and 3 occlusion rates were noted in 9 (53%), 6 (35%), and 2 (12%) of 17 aneurysms, respectively, indicating an 88% rate of complete or near complete occlusion. No cases of branch artery occlusion or distal emboli in the downstream vessels of the parent artery, specifically the subclavian artery, were seen. Parent artery compromise from neointimal hyperplasia was minimal in most cases. Conclusions— The Pipeline NED is a trackable, bio- and hemocompatible device able to occlude saccular aneurysms with preservation of the parent artery and small, adjacent branch vessels.

Background and Purpose— The purpose of this study was to determine whether implanting exogenous fibroblasts on platinum coils could enhance intra-aneurysmal fibrosis. Hypotheses included: (1) fibroblast-coated (FBC) platinum coils can improve angiographic results after embolization; and (2) FBC platinum coils can accelerate histological healing of embolized aneurysms. Methods— Experimental aneurysms in rabbits were embolized with control platinum coils (n=18) or FBC coils (n=18). Subjects were euthanized at 14 days, 1 month, 3 months and 6 months after implantation. Digital subtraction angiography was used to evaluate stability after embolization. Histological samples were examined with a grading system (range, 0 to 12) based on neck and dome healing. Results— Histology total scores and fibrosis ratio at 14 days were significantly greater in the FBC coil group compared with controls (6.6±1.9 versus 2.5±1.1, 1.2±0.6% versus 0.2±0.3%, respectively; P =0.0090). Cavities embolized with FBC coils showed cellular proliferation and thrombus organization, with an endothelialized membrane bridging the neck. There were no differences between groups in the later timepoints. The FBC coil group showed radiographic stability in 11 (61%) cases, coil compaction in 2 (11%) cases, and progressive occlusion in 5 (28%) cases. No progressive occlusion was seen in controls; 3 (17%) of 18 control cases exhibited coil compaction ( P =0.0546). Conclusions— FBC coils can accelerate early histological healing compared with control coils in the rabbit aneurysm model.