Carotid baroreceptor stimulation to treat resistant hypertension

Background

Resistant hypertension occurs when 1) use of at least three antihypertensive drugs at full daily dosage - of which a diuretic- are unsuccessful in controlling blood pressure, and, having excluded pseudoresistance (white coat phenomenon), 2) contributing factors such as certain exogenous substances, or secondary causes of hypertension including hyperaldosteronism, obstructive sleep apnea, parenchymal and vascular kidney disease, pheochromocytoma, are possibly at work. Hypertension is resistant in 15-30% of study subjects and is often uncontrolled because of persistently elevated and isolated systolic hypertension. It is characterised by an excess in aldosterone and an increased intravascular volume. 
Renal sympathetic hyperactivity can cause hypertension to be maintained and even progress as the kidney is a source of central sympathetic outflow via renal nerve activity.
Pathophysiology of kidney function and interaction between the kidney and the brain, justifies the use of renal sympathetic denervation in the treatment of resistant hypertension and recent trials have corroborated this. (1-3) Previously in the e-journal, were published a review of the role of renal sympathetic nerves and denervation by Prof Tendera, on identification and management of resistant hypertension by Prof. Ruilope, as well as the initial clinical reports on denervation by Prof. Clement. 

Carotid baroreceptor stimulation

Recently an implantable device to electrically stimulate the carotid baroreceptors, to decrease sympathetic outflow (4), was used, and may have benefits in BP reduction in conditions with sympathetic nervous system predominance such as obesity (5), obstructive sleep apnoea (6), and isolated systolic hypertension (7). The electrical stimulation of carotid baroreceptors is a noninvasive procedure achieved by:

• An implantable bilateral carotid stimulator (electrodes) permanently placed in the perivascular space around the sinus of the carotid arteries;
• A pulse generator (battery-operated) subcutaneously implanted in the infraclavicular space;
• A computer system connected to the generator which controls the radiofrequency stimulation.

Blood pressure is lowered through sympathetic inhibition: the activation energy given from the device is conducted through the carotid leads to the carotid baroreceptors, which send signals to the brain, interpreted as a blood pressure rise; the brain sends signals to vessels, heart and kidneys to reduce blood pressure (8-10).  
The implanting of carotid electrodes in the perivascular space around the carotid sinus minimises effects on carotid chemoreceptors and reduces the damage to the carotid baroreceptor by avoiding dissection in the carotid bifurcation, therefore with no side effects. In addition, it has been shown that the chronic stimulation of the carotid baroreceptors does not cause injury, remodelling, or stenosis of the carotid arteries (11-12).
For proper placement of the electrodes a team of specialists hypertension, surgeons, anesthetists, and technicians, are needed as well as 1 to 2 days of hospital stay; antihypertensive drugs are withheld on the day of implantation, except for β-blockers.
Clinical trials on carotid receptor stimulation by an implantable device showed a significant reduction in both office systolic (22 or 34 mmHg) and diastolic (18 or 20 mmHg) blood pressure, 24-hour ambulatory blood pressure (14/9 mmHg), and heart rate (12 bpm), which was evident from study onset and was maintained at follow-up. Available data suggest a beneficial effect of carotid baroreceptor stimulation on the reversal of left ventricular hypertrophy and cardiac structure and function, with attenuated mitral A-valve velocity and reduced left atrial dimensions; also carotid baropacing does not impair the renal function of patients with resistant hypertension, even during prolonged follow-up periods (13-18).

Conclusions

Recently the implantation of a permanent bilateral perivascular carotid sinus pulse generator for carotid baroreceptor stimulation was used, causing sustained blood pressure and heart rate reduction, in patients with resistant hypertension.
Further clinical studies including large numbers of patients and detailed data on the long-term effects of the procedure are needed, to verify safety and efficacy of this new therapeutic approach.