The autonomic nervous system (ANS), through the interaction between the sympathetic and
vagal systems, plays a key role in modulating the cardiovascular system. Multiple
experimental data and clinical studies have shown that alterations in the activity of the
ANS - characterized by a predominant sympathetic modulation associated with reduced vagal
modulation - are implicated in the onset and progression of numerous cardiovascular
diseases. For example, both an increase in sympathetic activity and a reduction in vagal
activity are associated with an increased risk of death after myocardial infarction and
heart failure, and a further reduction in vagal activity has been shown to precede the
phases of hemodynamic instability (1 -2).
Over the last few years, the modulation of the ANS through the implantation of devices
has emerged as a new frontier for the treatment of heart failure (3). Although there is a
wide interest in the scientific community for the potential represented by this
therapeutic modality, nevertheless the different devices for neuromodulation therapy are
implantable devices (whose application requires an invasive procedure) and therefore not
free from risks and complications.
Direct stimulation of the vagus nerve by means of a sleeve positioned around the vagus
nerve in its right or left cervical portion and controlled by a pacemaker, represents one
of the methods proposed in the field of neuromodulation (4).
As for vagal stimulation, this can also be achieved non-invasively by applying an
external stimulator in the ear (5). Transcutaneous nerve stimulation is a widely used
procedure for the treatment of refractory epilepsy, while there is still limited
experience evaluating its cardiovascular effects. Preliminary data in healthy volunteers
have shown that: a) transcutaneous vagal stimulation, through the auricle, is able to
activate the afferent vagal pathway up to the nucleus of the solitary tract (6), b)
non-invasive stimulation of the vagus nerve is able to reduce sympathetic outflow (7).
Recent clinical experience suggests its role also in the control of paroxysmal atrial
fibrillation (8).
Therefore, non-invasive vagus nerve stimulation could be a promising therapeutic option
in the cardiovascular field.
This study aims to evaluate the effects of long-term transcutaneous vagus nerve
stimulation (tVNS) on autonomic parameters and other available physiological biomarkers
that reflect long-term adjustment of autonomic neural regulation and to correlate the
magnitude of the response to the baseline autonomic profile. A preliminary set of
experiments will be conducted on healthy subjects to define the best tVNS protocol (in
terms of frequency and site of stimulation) to induce acute changes in the autonomic
profile.