Endothelial Nitric Oxide Pathways in the Pathophysiology of Dengue: A Prospective Observational Study

Background: Dengue can cause increased vascular permeability that may lead to hypovolemic shock. Endothelial dysfunction may underlie this; however, the association of endothelial nitric oxide (NO) pathways with disease severity is unknown. Methods: We performed a prospective observational study in...

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Autor principal: Simmons, Cameron
Formato: Journal Article
Lenguaje:inglés
Publicado: 2018
Acceso en línea:https://demo7.dspace.org/handle/123456789/223
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author Simmons, Cameron
author_browse Simmons, Cameron
author_facet Simmons, Cameron
author_sort Simmons, Cameron
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description Background: Dengue can cause increased vascular permeability that may lead to hypovolemic shock. Endothelial dysfunction may underlie this; however, the association of endothelial nitric oxide (NO) pathways with disease severity is unknown. Methods: We performed a prospective observational study in 2 Vietnamese hospitals, assessing patients presenting early (<72 hours of fever) and patients hospitalized with warning signs or severe dengue. The reactive hyperemic index (RHI), which measures endothelium-dependent vasodilation and is a surrogate marker of endothelial function and NO bioavailability, was evaluated using peripheral artery tonometry (EndoPAT), and plasma levels of l-arginine, arginase-1, and asymmetric dimethylarginine were measured at serial time-points. The main outcome of interest was plasma leakage severity. Results: Three hundred fourteen patients were enrolled; median age of the participants was 21(interquartile range, 13-30) years. No difference was found in the endothelial parameters between dengue and other febrile illness. Considering dengue patients, the RHI was significantly lower for patients with severe plasma leakage compared to those with no leakage (1.46 vs 2.00; P < .001), over acute time-points, apparent already in the early febrile phase (1.29 vs 1.75; P = .012). RHI correlated negatively with arginase-1 and positively with l-arginine (P = .001). Conclusions: Endothelial dysfunction/NO bioavailability is associated with worse plasma leakage, occurs early in dengue illness and correlates with hypoargininemia and high arginase-1 levels.
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spelling oai:localhost:123456789-2232021-04-07T16:30:08Z Endothelial Nitric Oxide Pathways in the Pathophysiology of Dengue: A Prospective Observational Study Simmons, Cameron Background: Dengue can cause increased vascular permeability that may lead to hypovolemic shock. Endothelial dysfunction may underlie this; however, the association of endothelial nitric oxide (NO) pathways with disease severity is unknown. Methods: We performed a prospective observational study in 2 Vietnamese hospitals, assessing patients presenting early (<72 hours of fever) and patients hospitalized with warning signs or severe dengue. The reactive hyperemic index (RHI), which measures endothelium-dependent vasodilation and is a surrogate marker of endothelial function and NO bioavailability, was evaluated using peripheral artery tonometry (EndoPAT), and plasma levels of l-arginine, arginase-1, and asymmetric dimethylarginine were measured at serial time-points. The main outcome of interest was plasma leakage severity. Results: Three hundred fourteen patients were enrolled; median age of the participants was 21(interquartile range, 13-30) years. No difference was found in the endothelial parameters between dengue and other febrile illness. Considering dengue patients, the RHI was significantly lower for patients with severe plasma leakage compared to those with no leakage (1.46 vs 2.00; P < .001), over acute time-points, apparent already in the early febrile phase (1.29 vs 1.75; P = .012). RHI correlated negatively with arginase-1 and positively with l-arginine (P = .001). Conclusions: Endothelial dysfunction/NO bioavailability is associated with worse plasma leakage, occurs early in dengue illness and correlates with hypoargininemia and high arginase-1 levels. 2018-09-14T11:15:10Z 2017-11-09T04:05:28Z 2018-09-14T11:15:10Z 2017-06-20 2017-11-01 Journal Article https://demo7.dspace.org/handle/123456789/223 English
spellingShingle Simmons, Cameron
Endothelial Nitric Oxide Pathways in the Pathophysiology of Dengue: A Prospective Observational Study
title Endothelial Nitric Oxide Pathways in the Pathophysiology of Dengue: A Prospective Observational Study
title_full Endothelial Nitric Oxide Pathways in the Pathophysiology of Dengue: A Prospective Observational Study
title_fullStr Endothelial Nitric Oxide Pathways in the Pathophysiology of Dengue: A Prospective Observational Study
title_full_unstemmed Endothelial Nitric Oxide Pathways in the Pathophysiology of Dengue: A Prospective Observational Study
title_short Endothelial Nitric Oxide Pathways in the Pathophysiology of Dengue: A Prospective Observational Study
title_sort endothelial nitric oxide pathways in the pathophysiology of dengue a prospective observational study
url https://demo7.dspace.org/handle/123456789/223
work_keys_str_mv AT simmonscameron endothelialnitricoxidepathwaysinthepathophysiologyofdengueaprospectiveobservationalstudy