An Increased Endothelial‐Independent Vasodilation Is the Hallmark of the Neurally Mediated Syncope

Abstract

Background: The neurally mediated syncope (NMS) is sustained by complex cardiac and vascular reflexes, acting on and amplified by central autonomic loops, resulting in bradycardia and hypotension. Hypothesis: Our aim was to assess whether the pathophysiology of NMS is also related to an abnormal peripheral vasoreactivity. Methods: We evaluated by ultrasound the flow-mediated vasodilation (FMD) and the nitrate-mediated dilation (NMD) in 17 patients with NMS, induced by drug-free tilt test in 6 subjects and by nitrate-potentiated tilt test in the other 11 cases; the syncope was classified as vasodepressive (VD) in 8 cases, cardioinhibitory (CI) in 7, and mixed in 2. Results: The FMD was not different from controls (10.2 ± 4.5 vs 11.4 ± 3.9, P = ns), with normal recovery times; the NMD was greater in fainting subjects than in controls (26.7 ± 7.3 vs 19.0 ± 3.6, P < 0.05), with higher values in VD than in CI syncope (31.1 ± 7.0 vs 23.1 ± 5.0, P = ns); compared to controls, subjects with NMS showed normal recovery times after FMD but longer recovery times after nitrate administration (13.0 ± 5.6 vs 6.3 ± 0.7 minutes, P < 0.05). Conclusions:The evaluation of endothelial function supports evidence that NMS is characterized by a marked and sustained endothelial-independent vasodilation, in the presence of a normal FMD; vascular hyperreactivity in response to nitrate administration is particularly overt in vasodepressive syncope and can explain the high rate of responses to nitrate administration during tilt test.

Endothelial function in vasovagal syncope

“…Recent research has focused on the regulation of the peripheral circulation in patients with VVS in an attempt to identify the active or passive mechanism driving peripheral vasodilation [4][5][6].…”

“…Patients with VVS showed marked and sustained EID, in the presence of a normal FMD. Children with postural orthostatic tachycardia syndrome have also been shown to have augmented FMD and abnormal vascular endothelial function, which may play an important role in syncope induction [4,[12][13][14]. Studies by Wnuk and colleagues in our department indicated that increased FMD or EID, associated with abnormal endothelial function in the regulation of vascular wall tension after tilting of patients with VVS, are strong predictors of reflex syncope (submitted).…”

Postsynaptic α 1 -Adrenergic Vasoconstriction Is Impaired in Young Patients With Vasovagal Syncope and Is Corrected by Nitric Oxide Synthase Inhibition

“…nNOS has been localized to “nitrergic” nerves that proliferate within the gastrointestinal tract and distribute with the parasympathetic nervous system 29 . While local eNOS exerts endothelial mediated vascular effects which could directly mediate vasodilation in VVS 30;31 , NO released from nitrergic nerves can act at pre-junctional and post-junctional sites to reduce sympathetic transduction 32 . Effects are largest in the splanchnic vasculature 33 and in the kidney 34 where the density of nitrergic nerves is greatest, and are most potent during sympathetic activation.…”

Endothelial dysfunction state in migraine headache and neutrally mediated syncope in children and young adults

“…[ 7 ] Similar to the suggested basis for a migraine headache, an abnormal peripheral vasoreactivity has been shown to be associated with increased risk for syncope particularly in its neurally mediated type. [ 8 ]…”