Mark A. Danielson

Endovascular Treatment of Experimental Aneurysms by Use of Fibroblast-Coated Platinum Coils An Angiographic and Histopathologic Study

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.

Endovascular Treatment of Experimental Aneurysms with Use of Fibroblast Transfected with Replication-Deficient Adenovirus Containing Bone Morphogenetic Protein-13 Gene

BACKGROUND AND PURPOSE: Modified coils have failed to improve long-term recanalization of aneurysms. This study examined whether ex vivo transduction of replication-deficient adenovirus containing the bone morphogenetic protein-13 gene (Ad-BMP-13) in fibroblast allografts would improve angiographic results via increased collagen synthesis, compared with fibroblast-coated platinum coils (FBC) and bare platinum coils (PA). Materials and METHODS: Aneurysms were embolized with Ad-BMP-13-coated coils (n = 20). Rabbits were sacrificed at 14 days and at 1, 3, and 6 months after implantation. Digital subtraction angiography (DSA) evaluated stability after embolization. Histologic specimens were examined with a qualitative grading system. Masson trichrome evaluated collagen deposition. Findings were compared with previously reported controls for PA and FBC in the same model and time points. RESULTS: The grading system showed a greater total score (P = .0002) in Ad-BMP-13 (6.8 ± 1.6) and FBC (6.3 ± 2.4) compared with PA (4.7 ± 2.4). A group main effects test showed that aneurysm neck tissue coverage in Ad-BMP-13 (2.5 ± 1.1) was higher (P = .0007) than both FBC (1.6 ± 1.4) and PA (0.9 ± 1.1). Ad-BMP-13 had more (P < .0001) collagen deposition than the FBC and PA. One- and 3-month Ad-BMP-13 collagen depositions increased (P < .05) over the FBC and PA. Finally, Ad-BMP-13 showed radiographic stability in 15 (75%) cases, coil compaction in 4 (20%) cases, and progressive occlusion in 1 (5%) case. There were no differences in angiographic results (P = .6522). CONCLUSION: The Ad-BMP-13-coated coils can improve neck coverage and dome fibrosis in the rabbit model, even in the absence of observed differences in angiographic outcome.

Morbidity and Mortality Associated with Creation of Elastase-Induced Saccular Aneurysms in a Rabbit Model

BACKGROUND AND PURPOSE: Elastase-induced aneurysms in rabbits have been proposed as a useful preclinical tool for device development. The object of this study was to report rates of morbidity and mortality associated with the creation and embolization of elastase-induced rabbit aneurysms and to assess the impact of operator experience on these rates. MATERIALS AND METHODS: Elastase-induced model aneurysms were created in New Zealand white rabbits (n = 700). One neuroradiologist/investigator, naive to the aneurysm-creation procedure at the outset of the experiments, performed all surgeries. All morbidity and deaths related to aneurysm creation (n = 700) and embolization procedures (n = 529) were categorized into acute and chronic deaths. Data were analyzed with single-regression analysis and analysis of variance. To assess the impact of increasing operator experience, we broke the number of animals into 50-animal increments. RESULTS: There were 121 (17%) deaths among 700 subjects. Among 700 aneurysm-creation procedures, 59 deaths (8.4%) were noted. Among 529 aneurysm-embolization procedures, 43 deaths (8.1%) were noted. Nineteen additional deaths (2.7% of 700 subjects) were unrelated to the procedures. Simple regression-indicated mortality associated with procedures diminished with increasing operator experience (R2 = 0.38, P = .0180), and that for each 50-rabbit increment mortality was reduced, on average, by 0.6%. CONCLUSIONS: Mortality rates of approximately 8% are associated with both experimental aneurysm creation and with embolization in the rabbit elastase-induced aneurysm model. Increasing operator experience is inversely correlated with mortality, and the age of the rabbit is positively associated with morbidity.

Vascular anatomic variation in rabbits.

PURPOSE To explore the vascular anatomic variation along the aortic arch in New Zealand White rabbits with the goal of highlighting potential anatomic configurations that might be encountered in the performance of preclinical endovascular research in rabbits. MATERIALS AND METHODS Digital subtraction angiography images of the brachiocephalic artery (BCA) and aortic arch in New Zealand White rabbits were obtained after creation of elastase-induced aneurysms at the origin of the right common carotid artery (RCCA) in 214 animals. The patterns of origin of the RCCA and left common carotid artery (LCCA), right subclavian artery (RSCA) and left subclavian artery (LSCA), and right vertebral artery (RVA) and left vertebral artery (LVA) were analyzed. RESULTS Five predominant variations of vessel origin were identified. In 200 of 214 cases (93%), the LCCA originated from the bifurcation of the BCA and aorta. In eight cases (4%), the LCCA directly originated from the aorta. In two cases (1%), the LCCA originated from the BCA. Aberrant RSCA anatomy in which the RSCA originated from the aortic arch instead of the BCA was found in three cases (1.5%). In a single case (0.5%), aberrant RSCA anatomy with the RVA originating from the BCA was encountered. CONCLUSIONS Anatomic variation of the BCA in New Zealand White rabbits is similar to that seen in humans. Understanding of the normal and variant anatomy of the rabbit will aid investigators who use the rabbit model for endovascular research.