The novel 5-lipoxygenase inhibitor ABT-761 attenuates cerebral vasospasm in a rabbit model of subarachnoid hemorrhage
Autor(a) principal: | |
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Data de Publicação: | 2001 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.4/943 |
Resumo: | OBJECTIVE: Eicosanoids have been implicated in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). Leukotrienes, 5-hydroxyperoxyeicosatetraenoic acid, and 5-hydroxyeicosatetraenoic acid are part of this group of substances, resulting from the 5-lipoxygenase activity on arachidonic acid metabolism. This study examined the effects of ABT-761, a new 5-lipoxygenase inhibitor, on cerebral vasospasm in an in vivo rabbit model of SAH. METHODS: A total of 48 rabbits were assigned to one of six groups: SAH + placebo (n = 8), SAH + ABT-761 20 mg/kg (n = 8), SAH + ABT-761 30 mg/kg (n = 8), control + placebo (n = 8), control + ABT-761 20 mg/kg (n = 8), and control + ABT-761 30 mg/kg (n = 8). Drug administration was initiated 30 minutes after induction of SAH and repeated 24 hours later. The animals were killed 48 hours after SAH, using the perfusion-fixation method. The cross sectional areas of basilar artery histological sections were measured by an investigator blinded to the treatment groups of the individual samples. RESULTS: In placebo-treated animals, the average luminal cross sectional area of the basilar artery was reduced by 68% after SAH as compared with controls (P < 0.0001). After SAH, the vasospastic response was attenuated in animals treated with 20 or 30 mg/kg representing a 28 or 35% reduction, respectively (P = 0.0011 and P = 0.0038). CONCLUSION: The results demonstrated that ABT-761 is effective in attenuating experimental cerebral vasospasm, indicating that this new drug represents a potential therapeutic agent for the treatment of vasospasm after SAH. |
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The novel 5-lipoxygenase inhibitor ABT-761 attenuates cerebral vasospasm in a rabbit model of subarachnoid hemorrhageHemorragia SubaracnóideiaVasoespasmo IntracranianoOBJECTIVE: Eicosanoids have been implicated in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). Leukotrienes, 5-hydroxyperoxyeicosatetraenoic acid, and 5-hydroxyeicosatetraenoic acid are part of this group of substances, resulting from the 5-lipoxygenase activity on arachidonic acid metabolism. This study examined the effects of ABT-761, a new 5-lipoxygenase inhibitor, on cerebral vasospasm in an in vivo rabbit model of SAH. METHODS: A total of 48 rabbits were assigned to one of six groups: SAH + placebo (n = 8), SAH + ABT-761 20 mg/kg (n = 8), SAH + ABT-761 30 mg/kg (n = 8), control + placebo (n = 8), control + ABT-761 20 mg/kg (n = 8), and control + ABT-761 30 mg/kg (n = 8). Drug administration was initiated 30 minutes after induction of SAH and repeated 24 hours later. The animals were killed 48 hours after SAH, using the perfusion-fixation method. The cross sectional areas of basilar artery histological sections were measured by an investigator blinded to the treatment groups of the individual samples. RESULTS: In placebo-treated animals, the average luminal cross sectional area of the basilar artery was reduced by 68% after SAH as compared with controls (P < 0.0001). After SAH, the vasospastic response was attenuated in animals treated with 20 or 30 mg/kg representing a 28 or 35% reduction, respectively (P = 0.0011 and P = 0.0038). CONCLUSION: The results demonstrated that ABT-761 is effective in attenuating experimental cerebral vasospasm, indicating that this new drug represents a potential therapeutic agent for the treatment of vasospasm after SAH.RIHUCBarbosa, MDArthur, ASLouis, RHMacDonald, TPolin, RSGazak, CKassell, NF2011-01-20T16:00:52Z20012001-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.4/943engNeurosurgery. 2001 Nov;49(5):1205-12info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-11T14:22:08Zoai:rihuc.huc.min-saude.pt:10400.4/943Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:03:28.707060Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
The novel 5-lipoxygenase inhibitor ABT-761 attenuates cerebral vasospasm in a rabbit model of subarachnoid hemorrhage |
title |
The novel 5-lipoxygenase inhibitor ABT-761 attenuates cerebral vasospasm in a rabbit model of subarachnoid hemorrhage |
spellingShingle |
The novel 5-lipoxygenase inhibitor ABT-761 attenuates cerebral vasospasm in a rabbit model of subarachnoid hemorrhage Barbosa, MD Hemorragia Subaracnóideia Vasoespasmo Intracraniano |
title_short |
The novel 5-lipoxygenase inhibitor ABT-761 attenuates cerebral vasospasm in a rabbit model of subarachnoid hemorrhage |
title_full |
The novel 5-lipoxygenase inhibitor ABT-761 attenuates cerebral vasospasm in a rabbit model of subarachnoid hemorrhage |
title_fullStr |
The novel 5-lipoxygenase inhibitor ABT-761 attenuates cerebral vasospasm in a rabbit model of subarachnoid hemorrhage |
title_full_unstemmed |
The novel 5-lipoxygenase inhibitor ABT-761 attenuates cerebral vasospasm in a rabbit model of subarachnoid hemorrhage |
title_sort |
The novel 5-lipoxygenase inhibitor ABT-761 attenuates cerebral vasospasm in a rabbit model of subarachnoid hemorrhage |
author |
Barbosa, MD |
author_facet |
Barbosa, MD Arthur, AS Louis, RH MacDonald, T Polin, RS Gazak, C Kassell, NF |
author_role |
author |
author2 |
Arthur, AS Louis, RH MacDonald, T Polin, RS Gazak, C Kassell, NF |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
RIHUC |
dc.contributor.author.fl_str_mv |
Barbosa, MD Arthur, AS Louis, RH MacDonald, T Polin, RS Gazak, C Kassell, NF |
dc.subject.por.fl_str_mv |
Hemorragia Subaracnóideia Vasoespasmo Intracraniano |
topic |
Hemorragia Subaracnóideia Vasoespasmo Intracraniano |
description |
OBJECTIVE: Eicosanoids have been implicated in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). Leukotrienes, 5-hydroxyperoxyeicosatetraenoic acid, and 5-hydroxyeicosatetraenoic acid are part of this group of substances, resulting from the 5-lipoxygenase activity on arachidonic acid metabolism. This study examined the effects of ABT-761, a new 5-lipoxygenase inhibitor, on cerebral vasospasm in an in vivo rabbit model of SAH. METHODS: A total of 48 rabbits were assigned to one of six groups: SAH + placebo (n = 8), SAH + ABT-761 20 mg/kg (n = 8), SAH + ABT-761 30 mg/kg (n = 8), control + placebo (n = 8), control + ABT-761 20 mg/kg (n = 8), and control + ABT-761 30 mg/kg (n = 8). Drug administration was initiated 30 minutes after induction of SAH and repeated 24 hours later. The animals were killed 48 hours after SAH, using the perfusion-fixation method. The cross sectional areas of basilar artery histological sections were measured by an investigator blinded to the treatment groups of the individual samples. RESULTS: In placebo-treated animals, the average luminal cross sectional area of the basilar artery was reduced by 68% after SAH as compared with controls (P < 0.0001). After SAH, the vasospastic response was attenuated in animals treated with 20 or 30 mg/kg representing a 28 or 35% reduction, respectively (P = 0.0011 and P = 0.0038). CONCLUSION: The results demonstrated that ABT-761 is effective in attenuating experimental cerebral vasospasm, indicating that this new drug represents a potential therapeutic agent for the treatment of vasospasm after SAH. |
publishDate |
2001 |
dc.date.none.fl_str_mv |
2001 2001-01-01T00:00:00Z 2011-01-20T16:00:52Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.4/943 |
url |
http://hdl.handle.net/10400.4/943 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Neurosurgery. 2001 Nov;49(5):1205-12 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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