Sphingosine-1-Phosphate Treatment Can Ameliorate Microvascular Leakage Caused by Combined Alcohol Intoxication and Hemorrhagic Shock

Abstract Fluid resuscitation following hemorrhagic shock is often problematic, with development of prolonged hypotension and edema. In addition, many trauma patients are also intoxicated, which generally worsens outcomes. We directly investigated how alcohol intoxication impacts hemorrhagic shock an...

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Autores principales:	Travis M. Doggett, Natascha G. Alves, Sarah Y. Yuan, Jerome W. Breslin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2efab57d00b143b7892f765e64e6bf27
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spelling	oai:doaj.org-article:2efab57d00b143b7892f765e64e6bf272021-12-02T11:52:36ZSphingosine-1-Phosphate Treatment Can Ameliorate Microvascular Leakage Caused by Combined Alcohol Intoxication and Hemorrhagic Shock10.1038/s41598-017-04157-y2045-2322https://doaj.org/article/2efab57d00b143b7892f765e64e6bf272017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04157-yhttps://doaj.org/toc/2045-2322Abstract Fluid resuscitation following hemorrhagic shock is often problematic, with development of prolonged hypotension and edema. In addition, many trauma patients are also intoxicated, which generally worsens outcomes. We directly investigated how alcohol intoxication impacts hemorrhagic shock and resuscitation-induced microvascular leakage using a rat model with intravital microscopic imaging. We also tested the hypothesis that an endothelial barrier-protective bioactive lipid, sphingosine-1-phosphate (S1P), could ameliorate the microvascular leakage following alcohol intoxication plus hemorrhagic shock and resuscitation. Our results show that alcohol intoxication exacerbated hemorrhagic shock and resuscitation-induced hypotension and microvascular leakage. We next found that S1P effectively could reverse alcohol-induced endothelial barrier dysfunction using both cultured endothelial cell monolayer and in vivo models. Lastly, we observed that S1P administration ameliorated hypotension and microvascular leakage following combined alcohol intoxication and hemorrhagic shock, in a dose-related manner. These findings suggest the viability of using agonists that can improve microvascular barrier function to ameliorate trauma-induced hypotension, offering a novel therapeutic opportunity for potentially improving clinical outcomes in patients with multi-hit injuries.Travis M. DoggettNatascha G. AlvesSarah Y. YuanJerome W. BreslinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Travis M. Doggett Natascha G. Alves Sarah Y. Yuan Jerome W. Breslin Sphingosine-1-Phosphate Treatment Can Ameliorate Microvascular Leakage Caused by Combined Alcohol Intoxication and Hemorrhagic Shock
description	Abstract Fluid resuscitation following hemorrhagic shock is often problematic, with development of prolonged hypotension and edema. In addition, many trauma patients are also intoxicated, which generally worsens outcomes. We directly investigated how alcohol intoxication impacts hemorrhagic shock and resuscitation-induced microvascular leakage using a rat model with intravital microscopic imaging. We also tested the hypothesis that an endothelial barrier-protective bioactive lipid, sphingosine-1-phosphate (S1P), could ameliorate the microvascular leakage following alcohol intoxication plus hemorrhagic shock and resuscitation. Our results show that alcohol intoxication exacerbated hemorrhagic shock and resuscitation-induced hypotension and microvascular leakage. We next found that S1P effectively could reverse alcohol-induced endothelial barrier dysfunction using both cultured endothelial cell monolayer and in vivo models. Lastly, we observed that S1P administration ameliorated hypotension and microvascular leakage following combined alcohol intoxication and hemorrhagic shock, in a dose-related manner. These findings suggest the viability of using agonists that can improve microvascular barrier function to ameliorate trauma-induced hypotension, offering a novel therapeutic opportunity for potentially improving clinical outcomes in patients with multi-hit injuries.
format	article
author	Travis M. Doggett Natascha G. Alves Sarah Y. Yuan Jerome W. Breslin
author_facet	Travis M. Doggett Natascha G. Alves Sarah Y. Yuan Jerome W. Breslin
author_sort	Travis M. Doggett
title	Sphingosine-1-Phosphate Treatment Can Ameliorate Microvascular Leakage Caused by Combined Alcohol Intoxication and Hemorrhagic Shock
title_short	Sphingosine-1-Phosphate Treatment Can Ameliorate Microvascular Leakage Caused by Combined Alcohol Intoxication and Hemorrhagic Shock
title_full	Sphingosine-1-Phosphate Treatment Can Ameliorate Microvascular Leakage Caused by Combined Alcohol Intoxication and Hemorrhagic Shock
title_fullStr	Sphingosine-1-Phosphate Treatment Can Ameliorate Microvascular Leakage Caused by Combined Alcohol Intoxication and Hemorrhagic Shock
title_full_unstemmed	Sphingosine-1-Phosphate Treatment Can Ameliorate Microvascular Leakage Caused by Combined Alcohol Intoxication and Hemorrhagic Shock
title_sort	sphingosine-1-phosphate treatment can ameliorate microvascular leakage caused by combined alcohol intoxication and hemorrhagic shock
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2efab57d00b143b7892f765e64e6bf27
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Sphingosine-1-Phosphate Treatment Can Ameliorate Microvascular Leakage Caused by Combined Alcohol Intoxication and Hemorrhagic Shock

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