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Clin Infect Dis. 2017 Oct 16;65(9):1453-1461. doi: 10.1093/cid/cix567.

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

Author information

1
Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Hanoi and Ho Chi Minh City, Vietnam.
2
Department of Medicine, Imperial College London, United Kingdom.
3
Hospital for Tropical Diseases, Ho Chi Minh City.
4
National Hospital for Tropical Diseases, Hanoi, Vietnam.
5
Menzies School of Health Research, Darwin, Australia.
6
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
7
Nuffield Department of Medicine, University of Oxford, United Kingdom.
8
Department of Microbiology and Immunology, University of Melbourne, Australia.

Abstract

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.

KEYWORDS:

arginase; dengue; endothelial function; l-arginine; nitric oxide

PMID:
28673038
PMCID:
PMC5850435
DOI:
10.1093/cid/cix567
[Indexed for MEDLINE]
Free PMC Article

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