TY - JOUR
T1 - Endothelial Nitric Oxide Pathways in the Pathophysiology of Dengue
T2 - A Prospective Observational Study
AU - Yacoub, Sophie
AU - Lam, Phung Khanh
AU - Huynh, Trieu Trung
AU - Nguyen Ho, Hong Hanh
AU - Dong Thi, Hoai Tam
AU - Van Thu, Nguyen
AU - Lien, Le Thi
AU - Ha, Quyen Nguyen Than
AU - Le, Duyen Huynh Thi
AU - Mongkolspaya, Juthathip
AU - Culshaw, Abigail
AU - Yeo, Tsin Wen
AU - Wertheim, Heiman
AU - Simmons, Cameron
AU - Screaton, Gavin
AU - Wills, Bridget
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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.
AB - 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.
KW - arginase
KW - dengue
KW - endothelial function
KW - l -arginine
KW - nitric oxide
UR - http://www.scopus.com/inward/record.url?scp=85032861489&partnerID=8YFLogxK
U2 - 10.1093/cid/cix567
DO - 10.1093/cid/cix567
M3 - Article
C2 - 28673038
AN - SCOPUS:85032861489
SN - 1058-4838
VL - 65
SP - 1453
EP - 1461
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 9
ER -