Endothelial Nitric Oxide Pathways in the Pathophysiology of Dengue: A Prospective Observational Study. (29th June 2017)

• Record Type: Journal Article
• Authors: Yacoub, Sophie; Lam, Phung Khanh; Huynh, Trieu Trung; Nguyen Ho, Hong Hanh; Dong Thi, Hoai Tam; Van, Nguyen Thu; Lien, Le Thi; Ha, Quyen Nguyen Than; Le, Duyen Huynh Thi; Mongkolspaya, Juthathip; Culshaw, Abigail; Yeo, Tsin Wen; Wertheim, Heiman; Simmons, Cameron; Screaton, Gavin; Wills, Bridget
• Is Part Of: Clinical infectious diseases. Volume 65:Number 9(2017)
• Page Start: 1453
• Page End: 1461
• Publication Date: 2017-06-29
• Subjects: dengue -- endothelial function -- nitric oxide -- l-arginine -- arginase; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/cix567
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract : Endothelial dysfunction/reduced nitric oxide bioavailability is associated with worse plasma leakage in dengue patients and occurs early in the course of the disease. Endothelial dysfunction correlates with lower plasma l -arginine and higher arginase-1 levels. 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.