Sørland Kari, Sandvik Miriam Kristine, Rekeland Ingrid Gurvin, Ribu Lis, Småstuen Milada Cvancarova, Mella Olav, Fluge Øystein
Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.
Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway.
Front Med (Lausanne). 2021 Mar 22;8:642710. doi: 10.3389/fmed.2021.642710. eCollection 2021.
Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with a range of symptoms including post-exertional malaise (PEM), orthostatic intolerance, and autonomic dysfunction. Dysfunction of the blood vessel endothelium could be an underlying biological mechanism, resulting in inability to fine-tune regulation of blood flow according to the metabolic demands of tissues. The objectives of the present study were to investigate endothelial function in ME/CFS patients compared to healthy individuals, and assess possible changes in endothelial function after intervention with IV cyclophosphamide. This substudy to the open-label phase II trial "Cyclophosphamide in ME/CFS" included 40 patients with mild-moderate to severe ME/CFS according to Canadian consensus criteria, aged 18-65 years. Endothelial function was measured by Flow-mediated dilation (FMD) and Post-occlusive reactive hyperemia (PORH) at baseline and repeated after 12 months. Endothelial function at baseline was compared with two cohorts of healthy controls ( = 66 and = 30) from previous studies. Changes in endothelial function after 12 months were assessed and correlated with clinical response to cyclophosphamide. Biological markers for endothelial function were measured in serum at baseline and compared with healthy controls ( = 30). Baseline FMD was significantly reduced in patients (median FMD 5.9%, range 0.5-13.1, = 35) compared to healthy individuals (median FMD 7.7%, range 0.7-21, = 66) ( = 0.005), as was PORH with patient score median 1,331 p.u. (range 343-4,334) vs. healthy individuals 1,886 p.u. (range 808-8,158) ( = 0.003). No significant associations were found between clinical response to cyclophosphamide intervention (reported in 55% of patients) and changes in FMD/PORH from baseline to 12 months. Serum levels of metabolites associated with endothelial dysfunction showed no significant differences between ME/CFS patients and healthy controls. Patients with ME/CFS had reduced endothelial function affecting both large and small vessels compared to healthy controls. Changes in endothelial function did not follow clinical responses during follow-up after cyclophosphamide IV intervention.
肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）患者会出现一系列症状，包括运动后不适（PEM）、体位性不耐受和自主神经功能障碍。血管内皮功能障碍可能是一种潜在的生物学机制，导致无法根据组织的代谢需求对血流调节进行微调。本研究的目的是调查ME/CFS患者与健康个体相比的内皮功能，并评估静脉注射环磷酰胺干预后内皮功能的可能变化。这项针对开放标签II期试验“ME/CFS中的环磷酰胺”的子研究纳入了40例根据加拿大共识标准诊断为轻度至中度至重度ME/CFS的患者，年龄在18至65岁之间。在基线时通过血流介导的血管舒张（FMD）和闭塞后反应性充血（PORH）测量内皮功能，并在12个月后重复测量。将基线时的内皮功能与先前研究中的两组健康对照（n = 66和n = 30）进行比较。评估12个月后内皮功能的变化，并将其与环磷酰胺的临床反应相关联。在基线时测量血清中内皮功能的生物标志物，并与健康对照（n = 30）进行比较。与健康个体（中位数FMD 7.7%，范围0.7 - 21，n = 66）相比，患者（中位数FMD 5.9%，范围0.5 - 13.1，n = 35）的基线FMD显著降低（P = 0.005），PORH也如此，患者评分中位数为1,331 p.u.（范围343 - 4,334），而健康个体为1,886 p.u.（范围808 - 8,158）（P = 0.003）。在环磷酰胺干预的临床反应（55%的患者报告）与从基线到12个月的FMD/PORH变化之间未发现显著关联。ME/CFS患者与健康对照之间，与内皮功能障碍相关的血清代谢物水平无显著差异。与健康对照相比，ME/CFS患者的内皮功能降低，影响大血管和小血管。静脉注射环磷酰胺干预后的随访期间，内皮功能的变化与临床反应不一致。
