Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Hanoi and Ho Chi Minh City, Vietnam.
Department of Medicine, Imperial College London, United Kingdom.
Clin Infect Dis. 2017 Oct 16;65(9):1453-1461. doi: 10.1093/cid/cix567.
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.
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.
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).
Endothelial dysfunction/NO bioavailability is associated with worse plasma leakage, occurs early in dengue illness and correlates with hypoargininemia and high arginase-1 levels.
登革热可导致血管通透性增加，从而导致低血容量性休克。内皮功能障碍可能是其原因；然而，内皮一氧化氮（NO）途径与疾病严重程度的关系尚不清楚。
我们在越南的 2 家医院进行了一项前瞻性观察研究，评估了早期（发热<72 小时）就诊的患者和有警告症状或严重登革热的住院患者。使用外周动脉张力测定法（EndoPAT）评估反应性充血指数（RHI），该指数可衡量内皮依赖性血管舒张，是内皮功能和 NO 生物利用度的替代标志物，并在连续时间点测量 l-精氨酸、精氨酸酶-1 和非对称二甲基精氨酸的血浆水平。主要观察终点为血浆渗漏严重程度。
共纳入 314 例患者；参与者的中位年龄为 21 岁（四分位距，13-30 岁）。登革热和其他发热性疾病之间的内皮参数无差异。对于登革热患者，严重血浆渗漏患者的 RHI 明显低于无渗漏患者（1.46 比 2.00；P <.001），在急性发热期就已明显降低（1.29 比 1.75；P =.012）。RHI 与精氨酸酶-1 呈负相关，与 l-精氨酸呈正相关（P =.001）。
内皮功能障碍/NO 生物利用度与更严重的血浆渗漏有关，在登革热早期发生，并与低精氨酸血症和高精氨酸酶-1水平相关。
