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Hypertension
baroreceptors can reset to a higher activation threshold
17–19
and diminished implantable pulse generator (IPG) connected to bilateral carotid sinus leads
sensitivity.
20,21
The chronic activation of the SNS and its effects on a (CSLs).
26
Directional telemetry makes it possible to externally program the
systemic or on a regional organ-specific basis is important in the IPG, allowing adjustment of stimulation parameters.
26
These parameters
development of essential hypertension. The resetting of the baroreceptor include the amplitude of voltage and the frequency and duration of
attenuates the anticipated pressure-related inhibition of sympathetic impulses.
26
Activation energy is conducted from the IPG to the carotid
activity, preventing natural reflex control of elevated BP. sinuses by the CSLs, leading to stimulation of the baroreceptor fibers in the
carotid sinus wall and, consequently, stimulation of the baroreflex.
26,27
The
Baroreflex Activation—Pre-clinical Studies central nervous system perceives this increase in baroreceptor fiber
Lohmeier and colleagues have investigated the effect of carotid sinus activity in a manner such that sympathetic outflow decreases.
stimulation on BP regulation in canines. In their studies, electrodes were
chronically implanted around both carotid sinuses, with the electrodes Surgical Implantation Procedure
connected to an externally adjustable pulse generator.
22
Stimulation was The surgical implantation procedure for the Rheos System has been
carried out by using the pulse generator to electrically activate the carotid previously described in detail.
26,27
Briefly, on the day of the surgery the
baroreflex.
22
In these studies there was an early and considerable patient’s morning doses of antihypertensive medications are withheld.
reduction in mean arterial pressure (MAP) when the baroreceptors were Aspirin and beta-adrenergic blockers are administered unless
chronically stimulated.
22
This reduction was maintained throughout the contraindicated. The surgical procedure is carried out under general
seven days of baroreflex activation,
22
indicating a short-term durable anesthesia. The first stage involves anesthetic induction and exposure of
response. There was also a decrease in plasma noradrenaline the carotid bifurcation. This is followed by carotid sinus mapping on each
concentration and heart rate (HR). The hemodynamic responses and side of the neck by identifying the location on the carotid sinus that when
plasma noradrenaline concentration returned to baseline levels once the stimulated elicits the greatest drop in BP. Once identified, the electrodes
stimulation was terminated. Lohmeier et al. have shown similar results in (attached to the leads) are implanted at the best locations on each side.
canines with an obesity-related model of hypertension.
23
While sustained The CSLs are then subcutaneously tunnelled to the IPG and the IPG
BP lowering tends to activate the renin–angiotensin system with a implanted under the skin in a pocket on the right side of the chest beneath
subsequent angiotensin II-induced retention of salt and water,
8
no changes the collarbone. The time required for exposure of the carotid artery and
in renin levels were observed by Lohmeier and colleagues with carotid implantation of the pulse generator is similar to that involved in carotid
sinus stimulation in studies of experimentally induced hypertension in endarterectomy procedures and pacemaker implants, respectively.
various canine models.
17,23
These data suggest that a critical mechanism Placement of the electrodes in their optimal location and connection of the
through which carotid baroreflex stimulation results in long-term BP leads to the IPG may extend the procedure time by approximately one
regulation is renal sympatho-inhibition and, consequently, natriuresis, hour. This is determined largely by the carotid mapping stage and depends
despite there being lower BP. Lohmeier et al. have also tested the effect of on the anatomy of the carotid artery. As indicated, antihypertensive
renal denervation on the efficacy of carotid baroreflex stimulation in medications are administered in the post-operative period. One or two
canines.
13
They activated the carotid baroreflex for seven days before and days post-surgery, the device is activated to identify the settings that
after bilateral renal denervation and observed similar values for mean provide optimal BP lowering and the programming parameters are put in.
arterial pressure, plasma noradrenaline concentration, plasma renin The device is turned off for a month to allow time for wound healing and
activity, and sodium excretion before and after denervation. This indicates is reactivated after one month, when tests are carried out to determine the
the presence of mechanisms other than renal sympatho-inhibition that can best settings for the patient. The exact timing of device activation has, to
also help achieve long-term reductions in arterial pressure during chronic date, related to protocol-specific criteria.
baroreflex activation. The studies by Lohmeier and colleagues demonstrate
that in canine models chronic elevations of BP can be effectively regulated Baroreflex Activation in
by prolonged electrical stimulation of the carotid baroreflex. Hypertensive Patients
An early version of the Rheos device was evaluated in a proof-of-concept
A Novel Implantable Baroreflex study. The aim was to test whether carotid baroreflex stimulation using this
Activation System device was a treatment option for patients with resistant hypertension.
28
Despite initial promising findings, technical limitations hampered the early The study recruited 11 patients undergoing elective carotid surgery.
experiences with direct carotid sinus nerve stimulation in the 1970s.
24,25
Electrodes were placed on the carotid sinus wall. Once steady-state
Undesirable technical features included damage to the carotid sinus baseline levels of BP and HR were obtained, an electric current was
nerves during the surgical procedure and the potential for current spread applied to stimulate the baroreceptors (increased in one-volt increments).
around the implanted electrode. Moreover, the advent of newer and more A graded voltage-dependent and highly significant reduction in BP was
effective antihypertensive drugs contributed to a decline in interest in a observed upon acute electrical stimulation of the baroreceptors.
28
medical device approach. However, more recently interest has been
revived in the concept of non-pharmacological control of BP by prolonged The Device-based Therapy of
baroreflex activation, with the clinical evaluation of a novel implantable Hypertension Study
carotid sinus baroreceptor system (the Rheos
®
System, CVRx Inc, US). The Device-based Therapy of Hypertension (DEBuT-HT) study was designed
to evaluate the safety and efficacy of the Rheos System in severely
Mechanism of Action hypertensive patients despite treatment with multiple antihypertensive
The Rheos System is an externally programmable battery-powered drugs. It was a phase II European-based, open-label, single-group study.
30 US CARDIOLOGY
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