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Endovascular external carotid artery occlusion for brain selective targeting: a cerebrovascular swine model

BACKGROUND: The choice of an animal model for cerebrovascular research is often determined by the disease subtype to be studied (e.g. ischemic stroke, hemorrhage, trauma), as well as the nature of the intervention to be tested (i.e. medical device or pharmaceutical). Many initial studies are perform...

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Autores principales: Mangla, Sundeep, Choi, Jae H., Barone, Frank C., Novotney, Carol, Libien, Jenny, Lin, Erwin, Pile-Spellman, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687072/
https://www.ncbi.nlm.nih.gov/pubmed/26689288
http://dx.doi.org/10.1186/s13104-015-1714-7
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author Mangla, Sundeep
Choi, Jae H.
Barone, Frank C.
Novotney, Carol
Libien, Jenny
Lin, Erwin
Pile-Spellman, John
author_facet Mangla, Sundeep
Choi, Jae H.
Barone, Frank C.
Novotney, Carol
Libien, Jenny
Lin, Erwin
Pile-Spellman, John
author_sort Mangla, Sundeep
collection PubMed
description BACKGROUND: The choice of an animal model for cerebrovascular research is often determined by the disease subtype to be studied (e.g. ischemic stroke, hemorrhage, trauma), as well as the nature of the intervention to be tested (i.e. medical device or pharmaceutical). Many initial studies are performed in smaller animals, as they are cost-effective and their encephalic vasculature closely models that of humans. Non-human primates are also utilized when confirmation or validation is required on higher levels and to test larger devices. However, working with primates is complex and expensive. Intermediate sized animal models, such as swine and sheep, may represent a valuable compromise. Their cerebrovascular anatomy, however, comes with challenges because of the natural higher external carotid artery perfusion and the existence of a rete mirabile. We describe a modification to the traditional swine cerebrovascular model that significantly enhances selective brain hemispheric perfusion, limiting external carotid perfusion and dilution. RESULTS: We investigated whether unilateral endovascular coil-embolization of external carotid artery branches in swine would lead to increased brain perfusion, altering cerebral circulation so that it more closely models human cerebral circulation. Equal amounts of approximately 4 °C cold saline were injected in 6 Yorkshire pigs into the ipsilateral common carotid artery before and after embolization. Hemispheric temperature changes from pre- and post-embolization were obtained as a measure of brain perfusion and averaged and compared using non-parametric statistical tests (Wilcoxon signed rank test, Mann–Whitney U Test). Graphs were plotted with absolute changes in hemispheric temperature over time to determine peak temperature drop (PTD) and corresponding time to peak (TTP) following the cold bolus injection. There was a 288 ± 90 % increase in ipsilateral brain cooling after embolization indicating improved selective blood flow to the brain due to this vascular modification. CONCLUSION: We have developed an effective, selective vascular brain model in swine that may be useful as a practical and cost-reducing intermediate step for evaluating target dose–responses for central nervous system drugs and brain selective interventions, such as local hypothermia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13104-015-1714-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-46870722015-12-23 Endovascular external carotid artery occlusion for brain selective targeting: a cerebrovascular swine model Mangla, Sundeep Choi, Jae H. Barone, Frank C. Novotney, Carol Libien, Jenny Lin, Erwin Pile-Spellman, John BMC Res Notes Technical Note BACKGROUND: The choice of an animal model for cerebrovascular research is often determined by the disease subtype to be studied (e.g. ischemic stroke, hemorrhage, trauma), as well as the nature of the intervention to be tested (i.e. medical device or pharmaceutical). Many initial studies are performed in smaller animals, as they are cost-effective and their encephalic vasculature closely models that of humans. Non-human primates are also utilized when confirmation or validation is required on higher levels and to test larger devices. However, working with primates is complex and expensive. Intermediate sized animal models, such as swine and sheep, may represent a valuable compromise. Their cerebrovascular anatomy, however, comes with challenges because of the natural higher external carotid artery perfusion and the existence of a rete mirabile. We describe a modification to the traditional swine cerebrovascular model that significantly enhances selective brain hemispheric perfusion, limiting external carotid perfusion and dilution. RESULTS: We investigated whether unilateral endovascular coil-embolization of external carotid artery branches in swine would lead to increased brain perfusion, altering cerebral circulation so that it more closely models human cerebral circulation. Equal amounts of approximately 4 °C cold saline were injected in 6 Yorkshire pigs into the ipsilateral common carotid artery before and after embolization. Hemispheric temperature changes from pre- and post-embolization were obtained as a measure of brain perfusion and averaged and compared using non-parametric statistical tests (Wilcoxon signed rank test, Mann–Whitney U Test). Graphs were plotted with absolute changes in hemispheric temperature over time to determine peak temperature drop (PTD) and corresponding time to peak (TTP) following the cold bolus injection. There was a 288 ± 90 % increase in ipsilateral brain cooling after embolization indicating improved selective blood flow to the brain due to this vascular modification. CONCLUSION: We have developed an effective, selective vascular brain model in swine that may be useful as a practical and cost-reducing intermediate step for evaluating target dose–responses for central nervous system drugs and brain selective interventions, such as local hypothermia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13104-015-1714-7) contains supplementary material, which is available to authorized users. BioMed Central 2015-12-21 /pmc/articles/PMC4687072/ /pubmed/26689288 http://dx.doi.org/10.1186/s13104-015-1714-7 Text en © Mangla et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Technical Note
Mangla, Sundeep
Choi, Jae H.
Barone, Frank C.
Novotney, Carol
Libien, Jenny
Lin, Erwin
Pile-Spellman, John
Endovascular external carotid artery occlusion for brain selective targeting: a cerebrovascular swine model
title Endovascular external carotid artery occlusion for brain selective targeting: a cerebrovascular swine model
title_full Endovascular external carotid artery occlusion for brain selective targeting: a cerebrovascular swine model
title_fullStr Endovascular external carotid artery occlusion for brain selective targeting: a cerebrovascular swine model
title_full_unstemmed Endovascular external carotid artery occlusion for brain selective targeting: a cerebrovascular swine model
title_short Endovascular external carotid artery occlusion for brain selective targeting: a cerebrovascular swine model
title_sort endovascular external carotid artery occlusion for brain selective targeting: a cerebrovascular swine model
topic Technical Note
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687072/
https://www.ncbi.nlm.nih.gov/pubmed/26689288
http://dx.doi.org/10.1186/s13104-015-1714-7
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