Effect of Transcutaneous Vagal Stimulation (TVS) on Endothelial Function in PAD

Peripheral arterial disease (PAD) constitutes a major public health burden. The incidence of
PAD increases with age and is associated with other comorbid cardiovascular disorders.
Atherosclerosis which underlies PAD is associated with increased arterial stiffness and an
enhanced inflammatory state as evidenced by increased levels of pro-inflammatory cytokines
and markers. One the earliest signs of cardiovascular disease is endothelial dysfunction
which is characterized by a decreased vasodilatory capacity of the vascular endothelium and
this lesion predates the development of clinical atherosclerosis. Endothelial dysfunction has
been shown to be widely prevalent in PAD. It is postulated that endothelial dysfunction is
due to enhanced sympathetic drive, diminished parasympathetic drive, chronic inflammatory
state all of which leads to reduced nitric oxide synthase activity in the vascular
endothelium with subsequent loss of vasodilatory capacity. Studies have shown endothelial
dysfunction to be reversible with pharmaco-therapeutic interventions, though these
interventions are associated with their own adverse effects. Stimulation of Vagal nerve
increases the parasympathetic activity while suppressing sympathetic drive, decreases
inflammation and enhancing nitric oxide synthase activity. Recent experimental and clinical
data suggest that low-level tragus nerve stimulation (by stimulating the auricular branch of
the vagus nerve located at the tragus of the external ear) may produce the same desired
neuromodulator effect compared to vagus nerve stimulation. It is however unknown if
Transcutaneous Vagal Stimulation (TVS) would lead to improved endothelial function as
measured by flow mediated dilatation (FMD) and laser speckle contrast imaging(LSCI), a
non-invasive method of measuring endothelial function or decrease in arterial stiffness as
measured by Pulse Wave Analysis (PWA), in patients with PAD. The objective of this study is
to determine the impact of TVS on endothelial dysfunction as measured by FMD & LSCI and
arterial stiffness. Study population will include patients with established diagnosis of PAD.
After performing baseline FMD, LSCI and PWA patients will be randomized to TVS and sham
stimulation with cross over. The patient randomized to TVS stimulation will obtain
stimulation for 1 hour followed by measurement of FMD,LSCI and PWA. There will be a washout
period of at least 24 hours with patient crossing over to the other arms thus serving as
their self-control.