Aspirin and Clopidogrel Inhibit Aneurysm Healing after HydroCoil Implantation in External Carotid Artery Aneurysm Model Chao Zhang, MD, Peiliang Li,

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Aspirin and Clopidogrel Inhibit Aneurysm Healing after HydroCoil Implantation in External Carotid Artery Aneurysm Model Chao Zhang, MD, Peiliang Li, MD, Guohua Xi, MD, Joseph J. Gemmete, MD, Neeraj Chaudhary, MRCS, FRCR, B. Gregory Thompson, MD, Aditya S. Pandey, MD Journal of Stroke and Cerebrovascular Diseases Volume 25, Issue 11, Pages 2610-2618 (November 2016) DOI: 10.1016/j.jstrokecerebrovasdis.2016.07.001 Copyright © 2016 National Stroke Association Terms and Conditions

Figure 1 Percentage of organized tissue area in external carotid artery sacs harvested on day 14 following coil insertion among the different antiplatelet medication groups. Within the bare platinum coil groups (n = 5), the organized tissue area was not affected by antiplatelet administration (aspirin versus saline, P = .83; clopidogrel versus saline, P = .46; aspirin + clopidogrel versus saline, P = .54). For the HydroCoil groups (n = 5), the organized tissue area was significantly reduced (aspirin versus saline, P = .02; clopidogrel versus saline, P = .04; aspirin + clopidogrel versus saline, P = .02) in rats treated with antiplatelet agents; however, no difference was found among type or combination of antiplatelets administered (aspirin versus clopidogrel, P = .8; aspirin versus aspirin + clopidogrel, P = .3; clopidogrel versus aspirin + clopidogrel, P = .5). Journal of Stroke and Cerebrovascular Diseases 2016 25, 2610-2618DOI: (10.1016/j.jstrokecerebrovasdis.2016.07.001) Copyright © 2016 National Stroke Association Terms and Conditions

Figure 2 Hematoxylin-and-eosin-stained sections from external carotid artery sacs harvested on day 14 following platinum coil insertion. Top row, control group; second row, aspirin group; third row, clopidogrel group; bottom row, aspirin + clopidogrel group. Original magnification 10×; scale bars = 200 µm. Journal of Stroke and Cerebrovascular Diseases 2016 25, 2610-2618DOI: (10.1016/j.jstrokecerebrovasdis.2016.07.001) Copyright © 2016 National Stroke Association Terms and Conditions

Figure 3 Hematoxylin-and-eosin-stained sections from external carotid artery sacs harvested on day 14 following HydroCoil insertion. Top row, control group; second row, aspirin group; third row, clopidogrel group; bottom row, aspirin + clopidogrel group. Original magnification 10×; scale bars = 200 µm. Journal of Stroke and Cerebrovascular Diseases 2016 25, 2610-2618DOI: (10.1016/j.jstrokecerebrovasdis.2016.07.001) Copyright © 2016 National Stroke Association Terms and Conditions

Figure 4 Percentage of residual elastic lamina in external carotid artery sacs harvested on day 14 following coil insertion among the different antiplatelet medication groups. No statistically significant difference was seen among different antiplatelet medication groups with either bare platinum coil (aspirin versus saline, P = .057; clopidogrel versus saline, P = .055; aspirin + clopidogrel versus saline, P = .29; aspirin versus clopidogrel, P = .5; aspirin versus aspirin + clopidogrel, P = .35; clopidogrel versus aspirin + clopidogrel, P = .57) or HydroCoil insertion (aspirin versus saline, P = .78; clopidogrel versus saline, P = .82; aspirin + clopidogrel versus saline, P = .54; aspirin versus clopidogrel, P = .99; aspirin versus aspirin + clopidogrel, P = .69; clopidogrel versus aspirin + clopidogrel, P = .73) (n = 5). Journal of Stroke and Cerebrovascular Diseases 2016 25, 2610-2618DOI: (10.1016/j.jstrokecerebrovasdis.2016.07.001) Copyright © 2016 National Stroke Association Terms and Conditions

Figure 5 Elastic van Gieson-stained sections from external carotid artery sacs harvested on day 14 following platinum coil insertion. Top row, control group; second row, aspirin group; third row, clopidogrel group; bottom row, aspirin + clopidogrel group. Original magnification 10×; scale bars = 200 µm. Journal of Stroke and Cerebrovascular Diseases 2016 25, 2610-2618DOI: (10.1016/j.jstrokecerebrovasdis.2016.07.001) Copyright © 2016 National Stroke Association Terms and Conditions

Figure 6 Elastic van Gieson-stained sections from external carotid artery sacs harvested on day 14 following HydroCoil insertion. Top row, control group; second row, aspirin group; third row, clopidogrel group; bottom row, aspirin + clopidogrel group. Original magnification 10×; scale bars = 200 µm. Journal of Stroke and Cerebrovascular Diseases 2016 25, 2610-2618DOI: (10.1016/j.jstrokecerebrovasdis.2016.07.001) Copyright © 2016 National Stroke Association Terms and Conditions

Figure 7 Immunohistochemical anti-CD68 stained sections revealing infiltration of macrophages within the wall of external carotid artery sacs harvested on day 14 following coil insertions. HydroCoils were associated with greater numbers of infiltrating macrophages than bare platinum coils (controls). The administration of single antiplatelet agents as well as dual antiplatelets led to inhibition of this response, as evident in the ASP, PLA, and ASP + PLA panels. Original magnification 10×; scale bars = 200 µm. Abbreviations: ASP, aspirin; PLA, plavix; ASP + PLA, aspirin and plavix. Journal of Stroke and Cerebrovascular Diseases 2016 25, 2610-2618DOI: (10.1016/j.jstrokecerebrovasdis.2016.07.001) Copyright © 2016 National Stroke Association Terms and Conditions